1.1.1.3 homoserine dehydrogenase drug development the enzyme might be a good target for anti-fungal drug development 1.1.1.3 homoserine dehydrogenase drug development HSD is an interesting metabolic target in the search for drugs with selective antifungal action and low toxicity to the host 1.1.1.21 aldose reductase drug development homochiral 3-hydroxy-4-substituted beta-lactams serve as precursors to the corresponding alpah-hydroxy-beta-amino acids, the enzyme might be useful insynthesis of these key components of many biologically and therapeutically important compounds 1.1.1.21 aldose reductase drug development the enzyme is a target for inhibitor design, enzyme inhibition has considerable potential for the treatment of diabetes, without increased risk of hypoglycemia 1.1.1.21 aldose reductase drug development the enzyme may be a potential drug target or vaccine candidate for schistosomes 1.1.1.21 aldose reductase drug development development of reductase inhibitors as drugs counteracting the onset of diabetic complications 1.1.1.23 histidinol dehydrogenase drug development histidinol dehydrogenase is a suitable target for not only for Geotrichum candidum but also for related species, wherby compounds identified can serve as a valuable lead for development of novel non-classical antifungal therapy, notably against strain like Candida rapidly becoming resistant to conventional therapy 1.1.1.23 histidinol dehydrogenase drug development histidinol dehydrogenase is a target for the development of antimicrobial agents 1.1.1.23 histidinol dehydrogenase drug development histidinol dehydrogenase is a target for the development of antimicrobial agents, overview 1.1.1.23 histidinol dehydrogenase drug development L-histidinol dehydrogenase from Brucella suis is an enzyme involved in the histidine biosynthesis pathway which is absent in mammals, thus representing a very interesting target for the development of anti-Brucella agents 1.1.1.25 shikimate dehydrogenase (NADP+) drug development the enzyme can be a target for rational design of specific inhibitors, aiming at the development of antitubercular drugs 1.1.1.25 shikimate dehydrogenase (NADP+) drug development shikimate dehydrogenase is an essential protein for the biosynthesis of the chorismate end product and is a highly promising therapeutic target, especially for the discovery and development of new-generation anti-tuberculosis agents 1.1.1.25 shikimate dehydrogenase (NADP+) drug development the enzyme is a target for antibacterial drug development 1.1.1.25 shikimate dehydrogenase (NADP+) drug development the essential enzyme is a potential target for antimicrobials 1.1.1.25 shikimate dehydrogenase (NADP+) drug development the essential enzyme is a potential target for herbicides and antimicrobials 1.1.1.25 shikimate dehydrogenase (NADP+) drug development the enzyme is a promising target for antituberculosis agent development 1.1.1.25 shikimate dehydrogenase (NADP+) drug development the enzyme is a target for drug development required for Acinetobacter baumannii, a member of ESKAPE pathogens, that has emerged as an extreme drug-resistant bacterium towards most of the current generation. Acinetobacter baumannii demonstrates resistance to nearly all major classes of antibiotics, including broad-spectrum penicillins, carbapenems, cephalosporins, fluoroquinolones, aminoglycosides, tetracyclines, chloramphenicol, and colistin, especially polymixin, creating a public health threat worldwide 1.1.1.27 L-lactate dehydrogenase drug development a selective lactate dehydrogenase inhibitor targeting the L-malate dehydrogenase function of Plasmodium falciparum and its corresponding tricarboxylic acid cycle provides an attractive therapeutic opportunity, in contrast to LDH targeting due to the functional similarity between human and parasite LDHs 1.1.1.27 L-lactate dehydrogenase drug development LDH is critically implicated in tumor growth and therefore considered to be an important target protein for antitumor metal complexes 1.1.1.27 L-lactate dehydrogenase drug development parasite LDH is a target for antimalarial compounds owing to structural and functional differences from the human isozymes 1.1.1.27 L-lactate dehydrogenase drug development LDH is a potential drug target and candidate antigen for immunodiagnosis (LDH can be recognized in serum from swine or patient infected with Taenia asiatica) and vaccine for taeniasis and viscero-cysticercosis caused by Taenia asiatica 1.1.1.27 L-lactate dehydrogenase drug development Sa-LDH-1 can become a potential drug target for antibiotics against Staphylococcus aureus 1.1.1.27 L-lactate dehydrogenase drug development the parasite enzyme is a potential target for antimalarial drugs 1.1.1.34 hydroxymethylglutaryl-CoA reductase (NADPH) drug development inhibitors of HMG-CoA reductase for reducing low density lipoprotein cholesterol in the treatment of hypercholesterolemia 1.1.1.34 hydroxymethylglutaryl-CoA reductase (NADPH) drug development a yeast expression system can serve to study the influence of selected mutations in human HMG-CoA reductase on the sensitivity of the enzyme to commonly prescribed statins, thus this model system is suitable for the development and selection of lipid-lowering drugs as well as for the examination of DNA sequence variations in the context of statin therapy 1.1.1.34 hydroxymethylglutaryl-CoA reductase (NADPH) drug development overexpression of HMGR appears promising for obtaining a constant high production of artemisinin, an effective drug against malaria for which no resistant strains of Plasmodium falciparum have been reported 1.1.1.37 malate dehydrogenase drug development mitochondrial malate dehydrogenase is a biological target for antiproliferative activity 1.1.1.B40 11beta-hydroxysteroid dehydrogenase (NAD+) drug development the enzyme is a target for inhibitor design and development 1.1.1.49 glucose-6-phosphate dehydrogenase (NADP+) drug development Trypanosoma brucei G6PDH is a valid drug target for human steroids. Inhibition of G6PDH by dehydroepiandrosterone derivatives may lead to the development of a new class of anti-trypanosomatid compounds 1.1.1.49 glucose-6-phosphate dehydrogenase (NADP+) drug development the enzyme is a target for anti-parasite drug development 1.1.1.50 3alpha-hydroxysteroid 3-dehydrogenase (Si-specific) drug development the enzyme is a target for treatment of chronic pain in neuropathic diseases, overview 1.1.1.51 3(or 17)beta-hydroxysteroid dehydrogenase drug development the steroidogenic enzyme 17beta-hydroxysteroid dehydrogenase type 3 (17beta-HSD3) is a therapeutic target in the management of androgen-sensitive diseases such as prostate cancer and benign prostate hyperplasia 1.1.1.62 17beta-estradiol 17-dehydrogenase drug development several 17beta-HSD isozymes are targets for drug development with importance in cancer, metabolic diseases, neurodegeneration and possibly immunity 1.1.1.62 17beta-estradiol 17-dehydrogenase drug development the enzyme is considered a promising drug target against estrogen-dependent cancers 1.1.1.62 17beta-estradiol 17-dehydrogenase drug development the enzyme constitutes an interesting therapeutic target for estrogen-dependent diseases 1.1.1.64 testosterone 17beta-dehydrogenase (NADP+) drug development testosterone is converted to 5alpha-dihydrotestosterone, which is present at high concentrations in patients with castration resistant prostate cancer (CRPC). Inhibition of 17beta-HSD5 is therefore considered to be a promising therapy for treating CRPC. High-throughput inhibitor screening, overview 1.1.1.86 ketol-acid reductoisomerase (NADP+) drug development the enzyme is a promising target for the design of herbicides 1.1.1.86 ketol-acid reductoisomerase (NADP+) drug development the enzyme is a target for herbicide drug development, computer-aided drug design 1.1.1.100 3-oxoacyl-[acyl-carrier-protein] reductase drug development the enzyme has no isoforms and thus is a good target for inhibitor design 1.1.1.100 3-oxoacyl-[acyl-carrier-protein] reductase drug development FabG is the antibacteria target of maple leaf extracts and tannic acid, and both reversible and irreversible inhibitions of FabG are important for the antibacterial effect 1.1.1.100 3-oxoacyl-[acyl-carrier-protein] reductase drug development galangal extract inhibits FabG, thereby displaying antibacterial ability 1.1.1.141 15-hydroxyprostaglandin dehydrogenase (NAD+) drug development induction of 15-hydroxyprostaglandin dehydrogenase expression or utilization of 15-keto-PGE2 analogue may have therapeutic benefits for the treatment of endotoxin-associated liver inflammation/injury 1.1.1.146 11beta-hydroxysteroid dehydrogenase drug development isozyme 11beta-HSD1 is a target in treatment of metabolic diseases such as diabetes mellitus type 2 or obesity 1.1.1.146 11beta-hydroxysteroid dehydrogenase drug development 11beta-HSD1 will significantly contribute to the biotransformation of oracin in humans. The microsomal carbonyl reductase has a great potential to significantly impair the chemotherapy with the anticancer drug oracin 1.1.1.184 carbonyl reductase (NADPH) drug development CBR1 inhibition can improve the therapeutic response to doxorubicin and reduce its side effects 1.1.1.184 carbonyl reductase (NADPH) drug development the cardioprotectant 7-monohydroxyethylrutoside inhibits CBR1 activity. CBR1 V88I genotype status and the type of anthracycline substrate dictate the inhibition of CBR1 activity. Inhibition of CBR1 activity shall be considered during the development of novel cardioprotectants against anthracycline-related cardiotoxicity 1.1.1.188 prostaglandin-F synthase drug development prostaglandin formation is a key component of PGaction and the specific target of non-steroidal anti-inflammatory drugs 1.1.1.205 IMP dehydrogenase drug development the enzyme is a potential therapeutic target, and the NAD+ site may be an exploitable target for the design of antimicrobial drugs 1.1.1.205 IMP dehydrogenase drug development the enzyme is a target for drug development in treatment of structural schizophrenia 1.1.1.205 IMP dehydrogenase drug development the enzyme is a target for therapeutic drugs 1.1.1.205 IMP dehydrogenase drug development the enzyme is a target in enzyme-pattern-targeted chemotherapy in acuet leukemia, AML, treatment 1.1.1.205 IMP dehydrogenase drug development the enzyme is a target in parasite treatment and elimination 1.1.1.205 IMP dehydrogenase drug development the IMPDH-1 is an antiangiogenic drug target 1.1.1.205 IMP dehydrogenase drug development 1,2,3-triazole IMPDH inhibitors provide new tools for elucidating the role of IMPDH in Cryptosporidium parvum and may serve as potential therapeutics for treating cryptosporidiosis 1.1.1.205 IMP dehydrogenase drug development at therapeutic concentrations in organ transplant patients, the effect of mycophenolic acid-acyl-glucuronide on IMPDHII activity is minimal compared to mycophenolic acid, and the quantification of mycophenolic acid metabolites for mycophenolate therapeutic drug monitoring and dose adjustment will be of no benefit 1.1.1.205 IMP dehydrogenase drug development differences between the human and Mycobacterium tuberculosis IMPDHs in the region of binding of nucleotide inhibitors on the inosine 5'-phosphate binding site. These and other differences, may be exploited for the design of new inhibitors with selectivity against Mycobacterium tuberculosis IMPDH 1.1.1.205 IMP dehydrogenase drug development IMPDH2 is the major target for cancer chemotherapy 1.1.1.205 IMP dehydrogenase drug development Roche total mycophenolic acid assay (a new inosine monophosphate dehydrogenase inhibition assay) is a promising alternative for mycophenolic acid quantification where chromatographic methods are not available 1.1.1.205 IMP dehydrogenase drug development type I IMPDH is identified as an antiangiogenic drug target. Inhibition may cause endothelial cell cycle arrest 1.1.1.205 IMP dehydrogenase drug development IMPDH from Mycobacterium tuberculosis (MtIMPDH) is a potential molecular target to inhibitor development 1.1.1.205 IMP dehydrogenase drug development inosine 5'-monophosphate dehydrogenase 2 (IMPDH2) from Mycobacterium tuberculosis is an attractive drug target 1.1.1.205 IMP dehydrogenase drug development the enzyme IMPDH is a promising target for the treatment of Cryptosporidium infections 1.1.1.205 IMP dehydrogenase drug development the inhibition of IMPDH (leading to reduced cellular levels of guanine nucleotides) is an important strategy for antiproliferative, antiviral and antiparasitic effects. It is also a useful strategy for producing immunosuppression as IMPDH-dependent de novo synthesis of guanine nucleotides is responsible for maintaining the growth and differentiation of human B and T lymphocytes 1.1.1.213 3alpha-hydroxysteroid 3-dehydrogenase (Re-specific) drug development the enzyme is a target for treatment of chronic pain in neuropathic diseases, overview 1.1.1.213 3alpha-hydroxysteroid 3-dehydrogenase (Re-specific) drug development 2'-hydroxyflavanone may be useful for clinical therapy of malignancies where AKR1C3 is overexpressed like in prostate and breast cancer 1.1.1.252 tetrahydroxynaphthalene reductase drug development the enzyme represents a target for the development of fungicides and antimicotics 1.1.1.252 tetrahydroxynaphthalene reductase drug development flavonoids inhibit 3HNR, which can thus be considered a potential target for flavonoid action. In addition to being a known target for different fungicides, 3HNR can also serve as an interesting and novel target for the development of antimycotics 1.1.1.267 1-deoxy-D-xylulose-5-phosphate reductoisomerase drug development the enzyme is a potential target for antimalarial drug development and chemotherapy 1.1.1.267 1-deoxy-D-xylulose-5-phosphate reductoisomerase drug development the enzyme is a target for antibacterial agents and inhibitor design 1.1.1.267 1-deoxy-D-xylulose-5-phosphate reductoisomerase drug development the enzyme is an excellent drug target in a number of pathogenic organisms 1.1.1.267 1-deoxy-D-xylulose-5-phosphate reductoisomerase drug development Escherichia coli Dxr represents a valuable model enzyme for the screening for new antimalarial compounds, since work with the Plasmodium falciparum Dxr is associated with considerably high effort due to the instability of this enzyme and the low yield of the available recombinant expression system, no major differences in the IC50 between Escherichia coli Dxr and Plasmodium falciparum Dxr 1.1.1.267 1-deoxy-D-xylulose-5-phosphate reductoisomerase drug development 1-deoxy-D-xylulose-5-phosphate reductoisomerase in the nonmevalonate isoprene biosynthesis pathway is a target for developing antimalarial drugs 1.1.1.267 1-deoxy-D-xylulose-5-phosphate reductoisomerase drug development because the enzyme is absent in humans, DXR is a target for drug discovery 1.1.1.267 1-deoxy-D-xylulose-5-phosphate reductoisomerase drug development the enzyme is a target for the design of antimalarial drugs 1.1.1.267 1-deoxy-D-xylulose-5-phosphate reductoisomerase drug development enzyme DXR is a validated antimicrobial target 1.1.1.267 1-deoxy-D-xylulose-5-phosphate reductoisomerase drug development enzyme DXR is an antimicrobial target 1.1.1.267 1-deoxy-D-xylulose-5-phosphate reductoisomerase drug development the enzyme from Escherichia coli is a valuable target for the development of antimicrobial compounds 1.1.1.267 1-deoxy-D-xylulose-5-phosphate reductoisomerase drug development the enzyme from Mycobacterium smegmatis is a valuable target for the development of antimicrobial compounds 1.1.1.267 1-deoxy-D-xylulose-5-phosphate reductoisomerase drug development the methyl erythritol phosphate (MEP) pathway represents an attractive series of targets for antibiotic design, considering each enzyme of the pathway is both essential and has no human homologues, including enzymes DXP reductoisomerase (IspC) and MEP cytidylyltransferase (IspD) 1.1.1.282 quinate/shikimate dehydrogenase [NAD(P)+] drug development the essential enzyme is a potential target for herbicides and antimicrobials 1.1.1.357 3alpha-hydroxysteroid 3-dehydrogenase drug development testosterone is converted to 5alpha-dihydrotestosterone, which is present at high concentrations in patients with castration resistant prostate cancer (CRPC). Inhibition of 17beta-HSD5 is therefore considered to be a promising therapy for treating CRPC. High-throughput inhibitor screening, overview 1.1.3.6 cholesterol oxidase drug development the cytotoxicity activity against a few cancer cell lines, while broadly sparing the normal cells, suggests the possible use of this enzyme as a promising future contender for anticancer therapy 1.1.3.6 cholesterol oxidase drug development the enzyme showed significant cytotoxicity on breast (MCF-7), nasopharyngeal (KB) and ovarian (OVCAR) cancer cell lines at very low concentrations ranging from 0.000093 to 0.00014 mM. It exhibits relatively less cytotoxicity on primary mouse embryonic fibroblast (3T3) cells. Thus, cholesterol oxidase from Streptomyces sp. AKHSS could be a potential anticancer agent 1.1.3.15 (S)-2-hydroxy-acid oxidase drug development in humans the enzyme is a potential drug target for treatment of primary hyperoxaluria, a genetic disorder where overproduction of oxalate results in the formation of kidney stones 1.1.3.15 (S)-2-hydroxy-acid oxidase drug development isozyme Hao2 is a target for drug development in high blood pressure 1.2.1.11 aspartate-semialdehyde dehydrogenase drug development ASADH is a target for the development of novel antibiotics, especially for Gram-negative bacteria that require diaminopimelate for cell-wall biosynthesis 1.2.1.11 aspartate-semialdehyde dehydrogenase drug development ASADH family enzymes are attractive potential targets for development of antibiotics with novel modes of action 1.2.1.11 aspartate-semialdehyde dehydrogenase drug development the enzyme is a validated target for antimicrobial drug design 1.2.1.12 glyceraldehyde-3-phosphate dehydrogenase (phosphorylating) drug development as an essential enzyme for the survival of GBS, GAPDH may be a potential target for developing antibacterial drugs 1.2.1.12 glyceraldehyde-3-phosphate dehydrogenase (phosphorylating) drug development development of GAPDH inhibitors as anti-cancer and anti-parasitic agents 1.2.1.12 glyceraldehyde-3-phosphate dehydrogenase (phosphorylating) drug development Gapdh can be an effective target for anti-malarial chemotherapeutics 1.2.1.12 glyceraldehyde-3-phosphate dehydrogenase (phosphorylating) drug development Gapdh can be an effective target for anti-malarial chemotherapeutics. Enzyme PfGapdh shows an extra ligand binding capacity in the vicinity of the NAD+ binding region of the active site that may offer an opportunity to design and develop novel antimalarials 1.2.1.12 glyceraldehyde-3-phosphate dehydrogenase (phosphorylating) drug development GAPDH is an important drug target 1.2.1.12 glyceraldehyde-3-phosphate dehydrogenase (phosphorylating) drug development the conformation of FgGAPDH in this region is similar to the human enzyme. Therefore, GAPDH may not be a suitable target for drug discovery against fascioliasis caused by Fasciola gigantica 1.2.1.80 long-chain acyl-[acyl-carrier-protein] reductase drug development since the giant CpFAS1 and polyketide synthase CpPKS1 are structurally and functionally different from human Type I FAS, these parasite megasynthases may serve as novel drug targets, also because CpFAS1 and CpPKS1 utilize R domains to release final products 1.2.1.84 alcohol-forming fatty acyl-CoA reductase drug development FAR genes may be potential targets for pest control 1.3.1.2 dihydropyrimidine dehydrogenase (NADP+) drug development the enzyme is an adjunct target in cancer therapy since it rapidly breaks down the anti-cancer drug 5-fluorouracil and related compounds 1.3.1.6 fumarate reductase (NADH) drug development lack of NADH-fumarate reductase in mammalian cells provides an interesting target against Chagas disease 1.3.1.9 enoyl-[acyl-carrier-protein] reductase (NADH) drug development InhA is an attractive target for the development of drugs against tuberculosis 1.3.1.9 enoyl-[acyl-carrier-protein] reductase (NADH) drug development the bacterial enoyl-ACP reductase is a target for antibacterial drug development 1.3.1.10 enoyl-[acyl-carrier-protein] reductase (NADPH, Si-specific) drug development the bacterial enoyl-ACP reductase is a target for antibacterial drug development 1.3.1.92 artemisinic aldehyde DELTA11(13)-reductase drug development oral feeding of whole intact plant cells bioencapsulating the artemisinin reduces the Plasmodium falciparum parasitemia levels in challenged mice in comparison with commercial drug. The synergistic approache may facilitate low-cost production and delivery of artemisinin and other drugs through metabolic engineering of edible plants 1.3.3.4 protoporphyrinogen oxidase drug development protoporphyrinogen oxidase is one of the most important action targets of commercial herbicides 1.3.3.4 protoporphyrinogen oxidase drug development enzyme PPO is an excellent target for commercial herbicides 1.3.5.2 dihydroorotate dehydrogenase (quinone) drug development DHODH represents a potential target for anti-malarial therapy 1.3.8.2 4,4'-diapophytoene desaturase (4,4'-diapolycopene-forming) drug development the enzyme CrtN is an attractive and druggable target for fighting pigmented Staphylococcus aureus infections 1.4.1.2 glutamate dehydrogenase drug development although AtGDH1 is insensitive to MPD in activity assays, several (+/-)-2-methyl-2,4-pentanediol (MPD) binding sites with conserved sequence are identified and the observation of druggable sites opens a potential for non-competitive herbicide design 1.4.1.9 leucine dehydrogenase drug development construction of bifunctional formate dehydrogenase and leucine dehydrogenase enzymatic complex for efficient cofactor regeneration and L-tert leucine biotransformation. L-tert leucine is a widely used chiral building block in many asymmetric reactions for the synthesis of anti-tumor and anti-HIV drugs 1.4.3.1 D-aspartate oxidase drug development a DDO inhibitor that augments brain D-Asp levels can be a potent antipsychotic drug for the treatment of NMDA receptor-related disease 1.4.3.2 L-amino-acid oxidase drug development ACTX-6 demonstrates cytotoxicity in vitro and can inhibit tumor growth in vivo. It can markedly increase accumulation of sub-G1 phase, which suggests that this enzyme can induce apoptosis. ACTX-6 is a potential substance to develop into an antitumor drug 1.4.3.2 L-amino-acid oxidase drug development purified LAAO-I exhibits antiprotozoal activities which are demonstrated to be hydrogen-peroxide mediated. Exposure of promastigotes of Leishmania sp. results in dose-dependent parasite killing. LAAOs are interesting multifunctional enzymes, not only for a better understanding of the ophidian envenomation mechanism, but also due to their biotechnological potential as model for therapeutic agents 1.4.3.3 D-amino-acid oxidase drug development the enzyme is a drug target in schizophrenia 1.4.3.3 D-amino-acid oxidase drug development the enzyme is a potential therapeutic target for schizophrenia treatment 1.4.3.3 D-amino-acid oxidase drug development the enzyme is a target in schizophrenia treatment 1.4.3.4 monoamine oxidase drug development dual-target-directed drugs, compounds that inhibit MAO-B and antagonize A2A receptors, may have value in the management of Parkinson's disease, overview 1.4.3.4 monoamine oxidase drug development MAO-A is a target for a series of therapeutically valuable drugs. Thus, selective MAO-A inhibitors are used as antidepressants 1.4.3.4 monoamine oxidase drug development MAO-B is a target for a series of therapeutically valuable drugs. Thus, selective MAO-B inhibitors are used in the treatment of Parkinson’s disease 1.4.3.4 monoamine oxidase drug development indole and benzofuran derivatives are promising reversible MAO-B inhibitors with a possible role in the treatment of neurodegenerative diseases such as Parkinson’s disease 1.4.3.4 monoamine oxidase drug development active monoamine oxidase inhibitors represent suitable leads for the development of drugs for neurodegenerative and neuropsychiatric disorders such as Parkinson's disease and depression. Monoamine oxidase inhibitors are also of interest for the treatment of prostate cancer, certain types of cardiomyopathies and Alzheimer's disease 1.5.1.3 dihydrofolate reductase drug development enzyme is identical to enzyme from Bacillus anthracis. Use of enzyme as antimicrobial target for Bacillus anthracis, homology modelling of inhibitors and growth inhibition assays 1.5.1.3 dihydrofolate reductase drug development enzyme is identical to enzyme from Bacillus cereus. Use of enzyme from Bacillus cereus as antimicrobial target for Bacillus anthracis, homology modelling of inhibitors and growth inhibition assays 1.5.1.3 dihydrofolate reductase drug development comparison of Danio rerio and human enzyme to evaluate the suitability of the fish enzyme as an assay system for antifolate drug discovery. Structural and kinetic proterties of both enzymes are similar and susceptibilites to known inhibitors are also comparable 1.5.1.3 dihydrofolate reductase drug development comparison of Danio rerio and human enzyme to evaluate the suitability of the fish enzyme as an assay system for antifolate drug discovery. Structural and kinetic proterties of both enzymes are similar and susceptibilities to known inhibitors are also comparable 1.5.1.3 dihydrofolate reductase drug development expression of bifunctional dihydrofolate reductase-thymidylate synthase in plasmodium falciparum to assess interaction with antifolates 1.5.1.3 dihydrofolate reductase drug development modeling of 31 pyrimethamine derivatives into the active site of dihydrofolate reductase obtained from crystal structures 1J3I.pdb and 1J3K.pdb. Evaluation of predicted binding modes and key protein-ligand interactions 1.5.1.3 dihydrofolate reductase drug development modeling of 32 pyrimethamine derivatives into the active site of dihydrofolate reductase obtained from crystal structure 1J3K.pdb. Evaluation of predicted binding modes and key protein-ligand interactions 1.5.1.3 dihydrofolate reductase drug development receptor-based pharmacophore models based on ensembles of protein conformations from molecular dynamics simulations of enzyme in complex with NADPH in both the closed and open conformation of the M20 loop. Optimal models identify enzyme inhibitors over druglike noninhibitors. Model performance improves with increased dynamic sampling 1.5.1.3 dihydrofolate reductase drug development use of multiple protein structure technique for structure-based drug discovery. Construction of receptor-based pharmacophores using multiple X-ray crystallographic structures. Models incorporate a fair degree of protein flexibility and are highly selective for known inhibitors over drug-like non-inhibitors 1.5.1.3 dihydrofolate reductase drug development DHFR is a valid drug target 1.5.1.3 dihydrofolate reductase drug development mtDHFR is an attractive target for the development of anti-tuberculosis drugs 1.5.1.3 dihydrofolate reductase drug development the enzyme is a possible target for treatment of cryptosporidiosis caused by the organism 1.5.1.3 dihydrofolate reductase drug development the enzyme is a target for antifolate drugs. The parasite develops resistance to several used antifolates via mutations in the active site, e.g. point mutations of residues Ala16, Ile51, Cys59, Ser108 and Ile164, overview 1.5.1.3 dihydrofolate reductase drug development the enzyme is a target for drug development since the organism causes the opportunistic infection Pneumocystis pneumonia, a major cause of mortality in acquired immunodeficiency syndrome, AIDS, patients 1.5.1.3 dihydrofolate reductase drug development the enzyme is a target for drug development since the organism causes the opportunistic infection toxoplasmosis, a major cause of mortality in acquired immunodeficiency syndrome, AIDS, patients 1.5.1.3 dihydrofolate reductase drug development the enzyme is a target for inhibitor design, overview 1.5.1.3 dihydrofolate reductase drug development the essential enzyme is a target for development of specific inhibitors 1.5.1.3 dihydrofolate reductase drug development the essential enzyme is a target for development of specific inhibitors for treatment of the biodefense organism Bacillus anthracis 1.5.1.3 dihydrofolate reductase drug development the essential enzyme is a target for development of specific inhibitors for treatment of the causative agent in AIDS pneumonia 1.5.1.3 dihydrofolate reductase drug development dihydrofolate reductase is a potential drug target for the elimination of Brugia malayi, one of the three causative agents of lymphatic filariasis, a parasitic disease 1.5.1.3 dihydrofolate reductase drug development enzyme DHFR is an important drug target 1.5.1.3 dihydrofolate reductase drug development the enzyme is a target for drug development in the treatment of Human African trypanosomiasis (HAT), an infectious disease caused by two distinct subspecies of the protozoan parasite Trypanosoma brucei subsp. gambiense and Trypanosoma brucei subsp. rhodesiense 1.5.1.3 dihydrofolate reductase drug development the enzyme is an anti-parasitic drug target, e.g. for malaria or human cancers, because rapidly growing cells require folate to produce thymine 1.5.1.3 dihydrofolate reductase drug development the enzyme represents an attractive target for inhibitor design to disrupt systems that require rapid DNA turnover, e.g. proliferating cancer cells and pathogenic microbes 1.5.1.33 pteridine reductase drug development target for antifolate chemotherapy against Leishmania 1.5.1.33 pteridine reductase drug development target for antiparasite drug development 1.5.1.33 pteridine reductase drug development the enzyme is considered a promising target for anti-leishmanial drug development and several inhibitors that share the substrate scaffold 1.5.1.33 pteridine reductase drug development the classical antifolates targeting dihydrofolate reductase (DHFR) are ineffective towards trypanosomatid parasites owing to a metabolic bypass by the expression of pteridine reductase 1 (PTR1). The combined inhibition of PTR1 and DHFR activities in Trypanosoma parasites represents a promising strategy for the development of new effective treatments for human African trypanosomiasis (HAT) 1.5.1.39 FMN reductase [NAD(P)H] drug development enzyme ChuY is a potential target for the development of antibacterial or antivirulence drugs to combat not only UPEC but a broad range of pathogenic bacteria that contain chuY system or its orthologue, ranging from Vibrio to staphylococcal species 1.6.2.2 cytochrome-b5 reductase drug development flavonoids, regarding b5 reductase inhibition, indicate a potential for significant flavonoid–drug and/or flavonoid–xenobiotic interactions which may have important therapeutic and toxicological outcomes for certain drugs and/or xenobiotics. 1.6.5.2 NAD(P)H dehydrogenase (quinone) drug development ability of ketoconazole and itraconazole to induce NQO1 gene expression at the transcriptional level through an aryl hydrocarbon receptor-dependent mechanism 1.6.5.2 NAD(P)H dehydrogenase (quinone) drug development cytoprotective effect of bromocriptine involving PI3K- and Nrf2-mediated upregulation of the antioxidant enzyme NQO1, which may be a therapeutic strategy to protect cells from oxidative damage in Parkinson’s disease 1.6.5.2 NAD(P)H dehydrogenase (quinone) drug development design of novel lavendamycin analogues with enhanced, selective, and potent antitumor activity 1.6.5.2 NAD(P)H dehydrogenase (quinone) drug development greater induction activities of the phase II enzyme quinone reductase associated with stilbenoids serve as a useful starting point for the design of improved chemopreventive agents 1.6.5.2 NAD(P)H dehydrogenase (quinone) drug development in vitro, almond skin polyphenols act as antioxidants and induce quinone reductase activity, but these actions are dependent upon their dose, method of extraction, and interaction with antioxidant vitamins 1.6.5.2 NAD(P)H dehydrogenase (quinone) drug development induction of phase 2 enzymes, e.g. NQO1 increases resistance to chemical carcinogenesis. Isothiocyanates can therefore be valuable chemopreventative agents, and the specificity of these substances toward the urinary bladder suggest that they may be particularly useful for protecting against bladder cancer 1.6.5.2 NAD(P)H dehydrogenase (quinone) drug development mild temperature heat shock elevates the NQO1 expression in cancer cells, which in turn markedly increases the sensitivity of the cells to the bioreductive drug beta-lapachone in vitro and in vivo 1.6.5.2 NAD(P)H dehydrogenase (quinone) drug development NAD(P)H:quinone oxidoreductase is a major detoxifying enzyme for 7,12-dimethylbenz[a]anthracene. Eugenol has a potent protective effect against 7,12-dimethylbenz[a]anthracene-induced genotoxicity, presumably through the suppression of the 7,12-dimethylbenz[a]anthracene activation and the induction of its detoxification through NAD(P)H:quinone oxidoreductase 1.6.5.2 NAD(P)H dehydrogenase (quinone) drug development new coumarin-based competitive inhibitors of NQO1. NQO1 inhibition as an anticancer drug design target and superoxide generation as the dicoumarol-mediated mechanism of cytotoxicity 1.6.5.2 NAD(P)H dehydrogenase (quinone) drug development the enzyme is a valuable target for activating stimuli-responsive drug delivery systems based on quinone derivatives, such as prodrugs and liposomes 1.7.1.6 azobenzene reductase drug development azoreductases from enteric bacteria are targets in the development of drugs for the treatment of colon related disorders 1.7.1.7 GMP reductase drug development the enzyme is a target for the design of trypanocidal agents, e.g. based on mycophenolic acid 1.7.3.3 factor-independent urate hydroxylase drug development urate oxidase has the potential to be a therapeutic target for the treatment of gout 1.8.1.B1 thioredoxin glutathione reductase drug development identification of inhibitory compounds facilitates further development of anti-schistosomiasis drugs with novel mechanism of action 1.8.1.4 dihydrolipoyl dehydrogenase drug development a homology model for PfaE3 reveals an extra anti-parallel beta-strand at the position where human E3BP (E3-binding protein) interacts with E3, a parasite-specific feature that may be exploitable for drug discovery against pyruvate dehydrogenase complex, PDC. Plasmodium PDC is essential for parasite survival in the mosquito vector and for late liver stage development in the human host, suggesting its suitability as a target for intervention strategies against malaria 1.8.5.8 eukaryotic sulfide quinone oxidoreductase drug development the coenzyme Q-binding pocket in human SQOR is a druggable target, potential of SQOR inhibitors to provide a therapeutic approach for the treatment of heart failure patients with reduced ejection fraction (HFrEF) 1.8.5.8 eukaryotic sulfide quinone oxidoreductase drug development the enzyme is a target for structure-based drug design 1.8.98.2 sulfiredoxin drug development Srx may be a potential target for prevention or treatment of cancer, the colorimetric assay would be useful for high-throughput screening of Srx inhibitors as demonstrated 1.10.3.1 catechol oxidase drug development the enzyme is a target for development of specific inhibitors to avoid unfavorable enzymatic browning of plant-derived foods by tyrosinase causing decrease in nutritional quality and economic loss of food products 1.13.11.6 3-hydroxyanthranilate 3,4-dioxygenase drug development the enzyme is a a potential target in treating numerous disorders related to the concentration of quinolinic acid, the kynurenine pathway product 1.13.11.6 3-hydroxyanthranilate 3,4-dioxygenase drug development the enzyme is a target for pharmacological downregulation because it is involved in formation of quinolinic acid, a highly potent excitotoxin implicated in a number of neurodegenerative conditions 1.13.11.11 tryptophan 2,3-dioxygenase drug development the enzyme is a target for drug development 1.13.11.27 4-hydroxyphenylpyruvate dioxygenase drug development 4-hydroxyphenylpyruvate dioxygenase (HPPD), an essential enzyme in tyrosine catabolism, is an important target for treating type I tyrosinemia 1.13.11.27 4-hydroxyphenylpyruvate dioxygenase drug development 4-hydroxyphenylpyruvate dioxygenase is one of the most promising target sites for herbicide discovery 1.13.11.27 4-hydroxyphenylpyruvate dioxygenase drug development plant 4-hydroxyphenylpyruvate dioxygenase (HPPD) is the molecular target for development of specific inhibitors 1.13.11.27 4-hydroxyphenylpyruvate dioxygenase drug development the enzyme is a target for inhibitor and herbicide development 1.13.11.27 4-hydroxyphenylpyruvate dioxygenase drug development the enzyme is an important target for treating type I tyrosinemia and alkaptonuria due to its significant role in tyrosine catabolism 1.13.11.27 4-hydroxyphenylpyruvate dioxygenase drug development the human enzyme is a target for drug development in treatment of type 1 tyrosinemia, alkaptonuria, and hawkinsinuria, overvuew 1.13.11.31 arachidonate 12-lipoxygenase drug development cardiac 12/15-LOX is involved in the development of heart failure and inhibition of 12/15-LOX may be a novel treatment for this condition 1.13.11.31 arachidonate 12-lipoxygenase drug development induction of pro-carcinogenic 12-LOX pathway by an anticancer ceramide, which may be relevant to cancer biologists studying drug resistant tumors and devising potent anticancer therapeutic strategies to treat drug resistant tumors. Induction of 12-LOX pathway by ceramide may have implications in understanding pathophysiology of neurodegenerative diseases involving reactive oxygen species generation and inflammation 1.13.11.31 arachidonate 12-lipoxygenase drug development inhibition of 12/15-LOX provides robust protection against cell death preventing mitochondrial damage in oxidative stress-related brain injury 1.13.11.31 arachidonate 12-lipoxygenase drug development p12-LOX pathway may be an effective target of chemoprevention for skin carcinogenesis 1.13.11.33 arachidonate 15-lipoxygenase drug development 15-LO-1 is an attractive pharmacological target for treatment of inflammatory respiratory diseases like asthma, rhinitis and chronic obstructive pulmonary disease 1.13.11.33 arachidonate 15-lipoxygenase drug development systemic delivery of cholesterol-tagged siRNAs targeting 12/15-LO has renoprotective effects under diabetic conditions and therefore can be a novel therapeutic approach for diabetic nephropathy 1.13.11.33 arachidonate 15-lipoxygenase drug development trials of 15LO1 pathway inhibitors in asthma may be a promising treatment strategy 1.13.11.34 arachidonate 5-lipoxygenase drug development the enzyme is a target in drug design for cancer therapy, inhibitors inclinical trials, overview 1.13.11.34 arachidonate 5-lipoxygenase drug development the enzyme is an emerging target in obesity, insulin resistance, and artherosclerosis 1.13.11.34 arachidonate 5-lipoxygenase drug development caffeoyl clusters are good lead compounds in the design and synthesis of more potent 5-lipoxygenase inhibitors 1.13.11.34 arachidonate 5-lipoxygenase drug development due to their high potency against 5-lipoxygenase and the marked efficacy in biological systems, benzo[g]indole-3-carboxylates may have potential as anti-inflammatory therapeutics 1.13.11.34 arachidonate 5-lipoxygenase drug development gender difference in biosynthesis of leukotrienes (inflammatory mediators) may lead to new possibilities regarding development and use of 5-lipoxygenase inhibitors 1.13.11.34 arachidonate 5-lipoxygenase drug development pirinixic acid derivatives constitute a novel class of dual mPGES-1/5-lipoxygenase inhibitors with a promising pharmacologial profile and a potential for therapeutic use 1.13.11.34 arachidonate 5-lipoxygenase drug development 5-lipoxygenase (5-LOX) is a target for drug design. Due to its role in the production of inflammatory lipid mediators, 5-LOX is a target for the development of therapeutics for conditions as diverse as asthma, cardiovascular disease, pancreatic cancer, and traumatic brain injury 1.13.11.34 arachidonate 5-lipoxygenase drug development human 5-lipoxygenase is a well-validated target for anti-inflammatory therapy. Development of 5-LOX inhibitors with higher activities is highly required 1.13.11.52 indoleamine 2,3-dioxygenase drug development the enzyme is a target for drug development 1.13.11.52 indoleamine 2,3-dioxygenase drug development the enzyme is a promising therapeutic target of cancer 1.13.11.52 indoleamine 2,3-dioxygenase drug development therapeutic inhibition of IDO1 is receiving much attention due to its proposed role in the pathogenesis of several diseases including cancer, hypotension and neurodegenerative disorders 1.13.11.52 indoleamine 2,3-dioxygenase drug development increased levels of hIDO1 expression in tumor cells correlate with a poor prognosis for surviving several cancer types. hIDO1 is a drug target for cancer therapy, design of de novo inhibitors selective for hIDO1. 1.14.11.1 gamma-butyrobetaine dioxygenase drug development enzyme BBOX is a drug target for the treatment of myocardial infarction 1.14.11.2 procollagen-proline 4-dioxygenase drug development P4H is a target for therapeutic drug development in various pathologies, e.g. angiogenesis, fibrosis, ischemia, anemia, and hypoxia, overview 1.14.11.2 procollagen-proline 4-dioxygenase drug development the enzyme is a target for design of PHD inhibitors aimed at treating anemia and ischemic disease 1.14.11.11 hyoscyamine (6S)-dioxygenase drug development tropane alkaloids, such as hyoscyamine, 6-hydroxyhyoscyamine and scopolamine, are secondary metabolites that are traditionally applied in medicine due to their anticholinergic activity. An alternative strategy for the production of the most valuable alkaloids, 6beta-hydroxyhyoscyamine and scopolamine, using Escherichia coli harboring the hyoscyamine-6beta-hydroxylase enzyme as biocatalysts is developed 1.14.11.29 hypoxia-inducible factor-proline dioxygenase drug development the unique function of PHD2 makes it a prime target for selective inhibition leading to regulatory control of diseases such as cancer and stroke 1.14.11.30 hypoxia-inducible factor-asparagine dioxygenase drug development the unique function of FIH makes it a prime target for selective inhibition leading to regulatory control of diseases such as cancer and stroke 1.14.11.65 [histone H3]-dimethyl-L-lysine9 demethylase drug development the enzyme is a target for development of more potent JMJD1A/MALAT1 inhibitors for the prevention of tumor metastasis 1.14.13.2 4-hydroxybenzoate 3-monooxygenase drug development p-hydroxybenzoate hydroxylase (PobA) from Pseudomonas putida is a possible drug target to combat tetracycline resistance, in complex with flavin adenine dinucleotide (FAD) 1.14.13.8 flavin-containing monooxygenase drug development the enzyme is not affected by drugs in contrast to cytochrome P450 monooxygenases, EC 1.14.14.1, by incorporating FMO detoxication pathways into drug candidates, more drug-like materials may emerge 1.14.13.9 kynurenine 3-monooxygenase drug development enzyme KMO is an important drug target due to its role in regulating the levels of bioactive substances with contrasting effects. For treatment of central nervous related diseases, it is required that enzyme inhibitors should be both blood brain barrier permeable and should not cause hydrogen peroxide as a harmful side product. Molecular dynamics simulations and MM/GBSA calculations, overview 1.14.13.9 kynurenine 3-monooxygenase drug development importance of KMO as a drug target in neurological disease, benefits of brain permeable inhibitors in modulating kynurenine pathway metabolites in the central nervous system teeating brain neurological diseases 1.14.13.9 kynurenine 3-monooxygenase drug development KMO has been identified as a therapeutic target for limiting neuronal damage from ischemia and specific diseases. The inhibition of KMO in vivo has synergistic neuroprotective effects that include elevation of the concentration of kynurenate, that both slows glutamate release and antagonizes NMDA receptors, reducing aberrant excitation. Inhibition of KMO also has the added benefit of halting the accumulation of specific neurotoxic and/or apoptotic metabolites, such as 3-hydroxy-L-kynurenine and quinolinic acid 1.14.13.9 kynurenine 3-monooxygenase drug development the enzyme is a target for drug development in neurological, but also other, diseases, pharmacophore development with receptor-based pharmacophore modeling, detailed overview 1.14.13.16 cyclopentanone monooxygenase drug development immobilization in polyvinylalcohol gel particles is desirable technique with presumptive impact on industrial applications of recombinant whole-cell Baeyer–Villiger monooxygenases as biocatalysts for production of bioactive compounds and precursors of potentially new drugs. An immobilization of Escherichia coli cells with overproduced Baeyer-Villiger monooxygenase improves their stability in repetitive batch biooxidations as compared to free cells. Detected autoinduction of recombinant enzyme in pET22b+ plays a significant role in application of immobilized cells as it may increase specific activity of cells in repetitive use under growing reaction conditions. Original technique for qualitative analysis of enzyme expression within immobilized cells is developed 1.14.13.196 L-ornithine N5-monooxygenase [NAD(P)H] drug development essential for virulence, validating this enzyme as a drug target 1.14.14.17 squalene monooxygenase drug development possible enzyme to inhibit for treatment of hypercholesterolemia, but strong side effects (e.g. dermatitis-like toxicity) 1.14.14.18 heme oxygenase (biliverdin-producing) drug development the enzyme is a potential therapeutic target for antimicrobial drug development, computer-aided drug design and screening, overview 1.14.14.18 heme oxygenase (biliverdin-producing) drug development heme oxygenase has cytoprotective properties and may play a role in several disease states, making it an interesting therapeutic target 1.14.14.19 steroid 17alpha-monooxygenase drug development the enzyme is a target for inhibitor design 1.14.14.19 steroid 17alpha-monooxygenase drug development CYP17 is a target for inhibitor design as a target in treatment of prostate cancer 1.14.14.19 steroid 17alpha-monooxygenase drug development the enzyme is a target for drug development in treatment of prostate cancer, in which androgens play a pivotal role, overview 1.14.14.25 cholesterol 24-hydroxylase drug development generation of imidazo[1,2-a]pyridine analogues that effectively inhibit cholesterol 24-hydroxylase (CYP46A1). They can be used for prophylactic treatment of neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease 1.14.14.32 17alpha-hydroxyprogesterone deacetylase drug development regioisomeric 17beta-N-phenylpyrazolyl steroid derivatives have weak inhibitory effect on 17alpha-hydroxylase/C17,20-lyase 1.14.14.32 17alpha-hydroxyprogesterone deacetylase drug development silencing CYP17 expression may be a strategy for therapy of hyperandrogenism diseases, and also sets an example for the use of RNAi technology in endocrine diseases 1.14.14.83 geraniol 8-hydroxylase drug development co-overexpression of geraniol-10-hydroxylase and strictosidine synthase improves anti-cancer drug camptothecin accumulation in Ophiorrhiza pumila 1.14.14.154 sterol 14alpha-demethylase drug development CYP51 is a key target for fungal antibiotic therapy 1.14.14.154 sterol 14alpha-demethylase drug development CYP51 is a potential anticholesterolemic drug target 1.14.14.154 sterol 14alpha-demethylase drug development CYP51 is a prime target of antifungal drugs 1.14.14.154 sterol 14alpha-demethylase drug development the enzyme is a primary target in treatment of fungal infections in organisms ranging from humans to plants, and development of more potent and selective CYP51 inhibitors is an important biological objective 1.14.14.154 sterol 14alpha-demethylase drug development non-conservative Phe497 and Phe220 of CYP51 may be key residues for design of potent specific fungicides for CYP51 1.14.14.154 sterol 14alpha-demethylase drug development structural model of CYP51 can be used in azole optimization, virtual screening, or de novo inhibitor design for the discovery of new antifungal agents 1.14.14.154 sterol 14alpha-demethylase drug development the humanized yeast strain provides a useful tool for initial specificity testing for new drugs targeting CYP51 and clearly differentiates azole antifungals in a side-by-side comparison 1.14.14.167 (13S,14R)-13-O-acetyl-1-hydroxy-N-methylcanadine 8-hydroxylase drug development reconstitute of the noscapine gene cluster in Saccharomyces cerevisiae to achieve the microbial production of noscapine and related pathway intermediates 1.14.14.176 taxadiene 5alpha-hydroxylase drug development paclitaxel is a successful anticancer drug 1.14.15.3 alkane 1-monooxygenase drug development CYP4A may be a therapeutic target in the control of inflammatory, vascular, and liver diseases, as well as peroxisome disorders of fatty acid metabolism 1.14.15.4 steroid 11beta-monooxygenase drug development the enzyme is a target for development of selective and potent CYP11B2 inhibitors 1.14.15.6 cholesterol monooxygenase (side-chain-cleaving) drug development the vitamin D3 derivatives produced by the action of P450scc are good candidates for use in the therapy of hyperproliferative disorders 1.14.15.30 3-ketosteroid 9alpha-monooxygenase drug development the enzyme can be a target for inhibition in treatment of tuberculosis 1.14.16.4 tryptophan 5-monooxygenase drug development substituted 3-(4-(1,3,5-triazin-2-yl)-phenyl)-2-aminopropanoic acids as novel TPH1 inhibitors may provide novel treatments for gastrointestinal disorders associated with dysregulation of the serotonergic system, such as chemotherapy-induced emesis and irritable bowel syndrome 1.14.17.1 dopamine beta-monooxygenase drug development inhibitors of enzyme DBH nepicastat and etamicastat are currently in clinical development for treatment of cocaine dependence 1.14.18.1 tyrosinase drug development the enzyme is a target for development of specific inhibitors to avoid unfavorable enzymatic browning of plant-derived foods by tyrosinase causing decrease in nutritional quality and economic loss of food products 1.14.18.1 tyrosinase drug development 3-hydroxyphloretin and catechol isolated from the formosan apple, may be useful as cosmetic agents to stimulate skin whitening 1.14.18.1 tyrosinase drug development activators of tyrosinase with stimulatory effects on melanogenesis are beneficial for the treatment of hypopigmentation diseases. 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside is a potent tyrosinase activator and stimulator of melanogenesis with potential for the treatment of hypopigmentation disease 1.14.18.1 tyrosinase drug development activators of tyrosinase with stimulatory effects on melanogenesis are beneficial for the treatment of hypopigmentation diseases. THSG is a potent tyrosinase activator and stimulator of melanogenesis with potential for the treatment of hypopigmentation disease 1.14.18.1 tyrosinase drug development commercial plant extracts containing anthraquinones are being increasingly used for pharmaceuticals, foods and cosmetics due to their wide therapeutic and pharmacological properties 1.14.18.1 tyrosinase drug development inhibitor 1-hydroxy-3-phenylurea is a promising candidate for preclinical drug development for skin hyperpigmentation application 1.14.18.1 tyrosinase drug development kurarinol has the potential to be further developed as effective and safe anti-browning and skin-whitening agent 1.14.18.1 tyrosinase drug development the bark extract of Sideroxylon inerme, epigallocatechin gallate and procyanidin B1 warrant further investigation in clinical studies to be considered as skin-depigmenting agents 1.14.18.1 tyrosinase drug development the finding that mushroom extracts contain tyrosinase activity inhibition will contribute to better understanding of how their healing properties in various Chinese traditional herbal on skin care products. Tyrosinase inhibitors are effective components of skin-lightening compounds and cosmetics 1.14.18.1 tyrosinase drug development the inhibitor could be used as a skin whitening agent, but further evaluation of its cytotoxicity should be carried out to decide if it could be used safely as a therapeutic agent 1.14.18.1 tyrosinase drug development the suppression of tyrosinase activity by 2-butyl-5-hydroxyphenyl 3-(3,4-dihydroxyphenyl)propanoate and the inhibition of tyrosinase production by terrein appear to be an optimal combination for skin whitening 1.14.18.1 tyrosinase drug development tyrosinase inhibitors can be clinically useful for the treatment of some dermatological disorders associated with melanin hyperpigmentation 1.14.18.1 tyrosinase drug development tyrosinase is a key enzyme involved in melanin biosynthesis and of particular interest in repigmentation research 1.14.18.1 tyrosinase drug development acetazolamide is a good candidate for the inhibition of melanin biosynthesis. and might be used as a lead for developing the drugs for treatment of hyperpigmentary disorders and skin whitening 1.14.18.1 tyrosinase drug development the regulation of melanin synthesis via the inhibition of tyrosinase is a research topic in the context of preventing hyperpigmentation, thus tyrosinase inhibitors are increasingly important in the food, medical, and cosmetic industries. The evaluated suface plasmon resonance biosensor has the potential to be used in the detection and screening of inhibitor drug candidates 1.14.19.1 stearoyl-CoA 9-desaturase drug development isozyme SCD1 may represent a therapeutic target to control obesity and the progression of related metabolic diseases including type 2 diabetes and hepatic steatosis 1.14.19.1 stearoyl-CoA 9-desaturase drug development SCD-1 is a promising target for the treatment of cancer, skin disorders and metabolic diseases, development of clinical drug candidates 1.14.19.3 acyl-CoA 6-desaturase drug development the enzyme is a biological target for the discovery and development of pharmaceuticals to treat atherosclerosis 1.14.19.17 sphingolipid 4-desaturase drug development Des1 is a potential therapeutic target for combating HIV-1 infection 1.14.19.17 sphingolipid 4-desaturase drug development enzyme DES1 inhibition is used in treatment of cancer 1.14.19.17 sphingolipid 4-desaturase drug development enzyme DES1 inhibition is used in treatment of cancer, it is a target for fenretinide and fenretinide metabolites 1.14.99.29 deoxyhypusine monooxygenase drug development eIF5A and the hypusine biosynthetic enzymes are potential targets for intervention in aberrant cell proliferation 1.14.99.29 deoxyhypusine monooxygenase drug development the parasite enzyme is a potential target for antimalaria drug design 1.14.99.58 heme oxygenase (biliverdin-IX-beta and delta-forming) drug development the enzyme is a potential therapeutic target for antimicrobial drug development, computer-aided drug design and screening, overview 1.14.99.66 [histone H3]-N6,N6-dimethyl-L-lysine4 FAD-dependent demethylase drug development potential pharmacological value of LSD1 as a drug target originating from it being a flavin-dependent demethylase, rather than an iron-dependent enzyme of the Jumonji class 1.15.1.1 superoxide dismutase drug development the enzyme is a target for development of antiangiogenic and antitumour drugs 1.17.1.1 CDP-4-dehydro-6-deoxyglucose reductase drug development the enzyme is a drug target 1.17.1.8 4-hydroxy-tetrahydrodipicolinate reductase drug development enzyme is a potential target for new antimicrobial and herbicidal compounds 1.17.1.9 formate dehydrogenase drug development construction of bifunctional formate dehydrogenase and leucine dehydrogenase enzymatic complex for efficient cofactor regeneration and L-tert leucine biotransformation. L-tert leucine is a widely used chiral building block in many asymmetric reactions for the synthesis of anti-tumor and anti-HIV drugs 1.17.3.2 xanthine oxidase drug development the enzyme is a target for rational design of flavonoid-type inhibitors against xanthine oxidase useful for the treatment of hyperuricemia, gout, and inflammatory disease states 1.17.4.1 ribonucleoside-diphosphate reductase drug development the enzyme is an important therapeutic target for anticancer drugs 1.17.4.1 ribonucleoside-diphosphate reductase drug development class Ib NrdF requires manganese under conditions in which the organism is pathogenic. Considering that streptococci and other pathogens, including enterococci, staphylococci, and Bacillus sp., contain class Ib ribonucleotide reductase as their only aerobic RNR, prevention of dimanganese-tyrosyl radical (Mn(III)2-Y(*)) cofactor formation in the class Ib ribonucleotide reductase may be an attractive target for new antimicrobials 1.17.4.1 ribonucleoside-diphosphate reductase drug development ribonucleotide reductase is a key enzyme in DNA synthesis and cell growth control and represents an excellent target for anticancer therapy. 5'-O-valproyl-3'-C-methyladenosine inhibits ribonucleotide reductase activity by competing with ATP as an allosteric effector and concomitantly reduces the intracellular deoxyribonucleoside triphosphate pools. In contrast to previously used ribonucleotide reductase nucleoside analogs does not require intracellular kinases for its activity and therefore holds promise against drug resistant tumors with downregulated nucleoside kinases 1.17.4.1 ribonucleoside-diphosphate reductase drug development the thiazolyl hydrazones VG12, VG19, and VG22 plus arabinofuranosylcytosine might be able to improve conventional chemotherapeutic regimens for the treatment of human malignancies such as acute promyelocytic or chronic myelogenous leukemia 2.1.1.1 nicotinamide N-methyltransferase drug development the enzyme might be a good molecular target for lung cancer therapy 2.1.1.37 DNA (cytosine-5-)-methyltransferase drug development Dnmt inhibition is a promising strategy for the treatment of various developmental and proliferative diseases, particularly cancers 2.1.1.41 sterol 24-C-methyltransferase drug development inhibition studies as a powerful approach to rational design of new anti-sleeping sickness chemotherapeutic drugs 2.1.1.41 sterol 24-C-methyltransferase drug development newly synthesized azasterol derivates act at sites other than 24-SMT in Trypanosoma brucei 2.1.1.45 thymidylate synthase drug development the enzyme is a target for drug development in the treatement of Human African trypanosomiasis (HAT), an infectious disease caused by two distinct subspecies of the protozoan parasite Trypanosoma brucei subsp. gambiense and Trypanosoma brucei subsp. rhodesiense 2.1.1.56 mRNA (guanine-N7)-methyltransferase drug development cap methylation is a principal target of the antifungal activity of sinefungin 2.1.1.63 methylated-DNA-[protein]-cysteine S-methyltransferase drug development highly effective inactivation of MGMT by an oligodeoxyribonucleotide containing O6-(4-bromothenyl)guanine suggests that such oligodeoxyribonucleotides might have therapeutic applications if problems of delivery can be addressed 2.1.1.100 protein-S-isoprenylcysteine O-methyltransferase drug development the enzyme is a target for anticancer drug design 2.1.1.103 phosphoethanolamine N-methyltransferase drug development the enzyme is a potential target for development of inhibitors 2.1.1.148 thymidylate synthase (FAD) drug development unexpected observation that NADP+ competes with both FAD and substrate for the binding site in ThyX and displaces both molecules from the active site, opens avenues for the design of tight-binding inhibitors of ThyX enzymes from a variety of organisms 2.1.1.179 16S rRNA (guanine1405-N7)-methyltransferase drug development development of potent agents against 16S-RMTase producers as targets for treatment of multidrug resistant bacteria 2.1.1.220 tRNA (adenine58-N1)-methyltransferase drug development the enzyme crystal structures serve as templates for design of inhibitors that can be used to test tRNA m1A58 MTase's impact on retroviral priming and transcription 2.1.1.228 tRNA (guanine37-N1)-methyltransferase drug development TrmD has potential as a drug target 2.1.1.228 tRNA (guanine37-N1)-methyltransferase drug development the enzyme is a target for antibiotic development 2.1.1.228 tRNA (guanine37-N1)-methyltransferase drug development bacterial tRNA (guanine37-N1)-methyltransferase (TrmD) from Pseudomonas aeruginosa is a good target for development of antibacterial compounds 2.1.1.228 tRNA (guanine37-N1)-methyltransferase drug development bacterial tRNA modification synthesis pathways are critical to cell survival under stress and thus represent ideal mechanism-based targets for antibiotic development. tRNA-(N1G37) methyltransferase (TrmD) is a target, which is conserved and essential in many bacterial pathogens 2.1.1.228 tRNA (guanine37-N1)-methyltransferase drug development the enzyme is an attractive target for development of antibacterial drugs against Mycobacterium abscessus, which possesses both intrinsic and acquired resistance to available antibiotics and is therefore currently difficult or sometimes impossible to treat 2.1.1.228 tRNA (guanine37-N1)-methyltransferase drug development TrmD is a leading antimicrobial drug target, due to its essentiality for bacterial growth, its broad conservation across bacterial species, and its deep-rooted distinction from the human and archaeal counterpart Trm5, which has the dinucleotide fold 2.1.1.228 tRNA (guanine37-N1)-methyltransferase drug development TrmD is ranked as a high-priority antimicrobial target 2.1.1.244 protein N-terminal methyltransferase drug development design and synthesis of the inhibitors targeting NTMT1 as potential therapeutics in cancer treatment 2.1.1.244 protein N-terminal methyltransferase drug development the enzyme is a target for developing specific inhibitors 2.1.2.1 glycine hydroxymethyltransferase drug development the enzyme might be a a key target for the development of chemotherapic agents 2.1.2.1 glycine hydroxymethyltransferase drug development the enzyme represents a potential target for chemotherapeutics 2.1.2.1 glycine hydroxymethyltransferase drug development the human enzyme is a potential target for cancer treatment 2.1.2.3 phosphoribosylaminoimidazolecarboxamide formyltransferase drug development the enzyme is an important drug target 2.2.1.1 transketolase drug development non-permanently charged thiamine mimetics (thiamine analogs possessing B-rings unable to participate in the cycle) are competent substrates for thiamine pyrophosphokinase, and the resulting pyrophosphates antagonize the activity of transketolase in vitro. Despite remarkable potencies in enzymatic assays, cellular potencies are modest to poor. Inhibition of the thiamine-utilizing enzyme transketolase is linked with diminished tumor cell proliferation 2.2.1.1 transketolase drug development Plasmodium falciparum transketolase shows low homology with the host enzyme, thus may serve as a novel and promising target for designing inhibitors with anti-malarial activity 2.2.1.1 transketolase drug development ring-opened analogs of the transketolase inhibitor 'N30-pyridyl thiamine'; 3-(6-methyl-2-amino-pyridin-3-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-thiazol-3-ium chloride hydrochloride are effectively transformed in vivo to the active thiazoliums, whereby the effectiveness of this transformation is dependent on the sulfur moiety. The pharmacokinetic properties of the transketolase inhibitor are improved, the Cmax is reduced, thus avoiding toxicity, and higher distribution and exposure correlate in vivo with a stronger and longer inhibition of blood transketolase 2.2.1.1 transketolase drug development target for inhibition in the treatment of cancer 2.2.1.6 acetolactate synthase drug development the enzyme is a target for drug development 2.2.1.6 acetolactate synthase drug development AHAS is the target of the sulfonylurea and imidazolinone herbicides 2.2.1.6 acetolactate synthase drug development the enzyme is a target of several classes of herbicides 2.2.1.6 acetolactate synthase drug development the enzyme is an important target for design of environmental-benign herbicides 2.2.1.6 acetolactate synthase drug development the enzyme is the target of several herbicides 2.2.1.6 acetolactate synthase drug development the enzyme is the target of several herbicides, sulfonylureas, imidazolinones and other herbicides, structures of inhibitor-enzyme complexes explain the herbicide-enzyme interaction 2.2.1.6 acetolactate synthase drug development the enzyme is a target for development of herbicides, overview 2.2.1.6 acetolactate synthase drug development acetohydroxyacid synthase (AHAS) of Mycobacterium tuberculosis is a promising target for the development of anti-tuberculosis agents 2.2.1.6 acetolactate synthase drug development the enzyme is a target for drug development in tuberculosis treatment 2.2.1.6 acetolactate synthase drug development the enzyme is a target for the development of anti-tuberculosis agents 2.2.1.7 1-deoxy-D-xylulose-5-phosphate synthase drug development DXS is an attractive target for the development of antibiotics, antimalarials, and herbicides 2.3.1.5 arylamine N-acetyltransferase drug development inhibitors of NAT enzymes may be valuable as chemopreventive agents 2.3.1.5 arylamine N-acetyltransferase drug development the enzyme is a target for development of anti-mycobacterial drugs 2.3.1.20 diacylglycerol O-acyltransferase drug development the enzyme is a possible target for antilatency drugs 2.3.1.20 diacylglycerol O-acyltransferase drug development the enzyme is a target for development of inhibitors of lipid deposition 2.3.1.22 2-acylglycerol O-acyltransferase drug development [acyl CoA]monoacylglycerol acyltransferase 2 (MGAT2) is of interest as a target for therapeutic treatment of diabetes, obesity and other diseases which together constitute the metabolic syndrome 2.3.1.26 sterol O-acyltransferase drug development regulation of ACAT1 activities in hepatic stellate cells can be a target for treatment of liver fibrosis 2.3.1.26 sterol O-acyltransferase drug development selective inhibitors of the cholesterol esterifying enzyme sterol-O acyltransferase 2 (SOAT2) hold great promise as effective atherosclerotic cardiovascular disease therapeutics 2.3.1.26 sterol O-acyltransferase drug development the enzyme is a potential target for treating hypercholesterolemia 2.3.1.26 sterol O-acyltransferase drug development the enzyme is regarded as a potential therapeutic target for cardiovascular diseases 2.3.1.30 serine O-acetyltransferase drug development the essential requirement of serine acetyltransferase (SAT/CysE) for survival of several human pathogens makes it a very promising target for inhibitor designing and drug discovery, structure-based drug development, overview 2.3.1.31 homoserine O-acetyltransferase drug development possibilty to target the methionine biosynthesis pathway, which is not part of the host metabolism, through inhibition of the enzyme, structure-based drug design 2.3.1.35 glutamate N-acetyltransferase drug development the enzyme is a target for inhibition in treatment of Mycobacterium tuberculosis infection, e.g. inhibitor pranlukast (PRK) is highly effective against in vitro and in vivo survival of Mycobacterium tuberculosis and being an FDA-approved drug, it shows a potential for development of advanced combinatorial therapy against tuberculosis 2.3.1.39 [acyl-carrier-protein] S-malonyltransferase drug development the enzyme is a target for developing broad-spectrum antibiotics 2.3.1.41 beta-ketoacyl-[acyl-carrier-protein] synthase I drug development the enzyme is a target for antibacterial drugs 2.3.1.41 beta-ketoacyl-[acyl-carrier-protein] synthase I drug development the enzyme is a therapeutic target of designing antibiotics 2.3.1.41 beta-ketoacyl-[acyl-carrier-protein] synthase I drug development the enzyme is an attractive target for design of antibioticsis related to the elongation of unsat-urated fatty acids in bacterial fatty acid synthesis 2.3.1.43 phosphatidylcholine-sterol O-acyltransferase drug development LCAT is a potential drug target for reducing atherosclerosis 2.3.1.43 phosphatidylcholine-sterol O-acyltransferase drug development a therapeutic that increases enzyme LCAT activity may promote reverse cholesterol transport and prove beneficial for the treatment of dyslipidaemia and atherosclerosis 2.3.1.43 phosphatidylcholine-sterol O-acyltransferase drug development rational development of therapeutics to treat enzyme LCAT deficiency, atherosclerosis and acute coronary syndrome 2.3.1.B43 protein-lysine desuccinylase (NAD+) drug development SIRT5 is a drug target 2.3.1.B43 protein-lysine desuccinylase (NAD+) drug development Sirt5 is a potential drug target for the treatment of cancer, Alzheimer's disease, and Parkinson's disease 2.3.1.47 8-amino-7-oxononanoate synthase drug development the enzyme is a target for development of drugs against mycobac-terial pathogens 2.3.1.48 histone acetyltransferase drug development the enzyme is a unique target for therapeutic antifungal compounds 2.3.1.48 histone acetyltransferase drug development Tip60, the 60 kDa HIV-1 Tat-interactive protein, is a potential drug target 2.3.1.48 histone acetyltransferase drug development HBO1 is a potential anti-cancer target, design of HBO1-targeting molecules and their applications 2.3.1.57 diamine N-acetyltransferase drug development SSAT may also be a useful target in diseases other than cancer 2.3.1.67 1-alkylglycerophosphocholine O-acetyltransferase drug development identification of LPCAT2-specific inhibitors in order to ameliorate PAF-related inflammatory diseases, fluorescence-based high-throughput library screening 2.3.1.97 glycylpeptide N-tetradecanoyltransferase drug development NMT is a putative drug target 2.3.1.97 glycylpeptide N-tetradecanoyltransferase drug development the enzyme is a drug target 2.3.1.97 glycylpeptide N-tetradecanoyltransferase drug development the enzyme is a potential target for development of therapeutic agents against visceral leishmaniasis 2.3.1.97 glycylpeptide N-tetradecanoyltransferase drug development the enzyme is a target for drug design in the treatment of epilepsy 2.3.1.97 glycylpeptide N-tetradecanoyltransferase drug development the enzyme is a potential target for drug development 2.3.1.97 glycylpeptide N-tetradecanoyltransferase drug development the enzyme N-myristoyltransferase represents a promising drug target 2.3.1.107 deacetylvindoline O-acetyltransferase drug development vincristine and vinblastine are secondary metabolites from Catharanthus roseus with very high pharmacological value that are used in treating cancer. However, these compounds are synthesised in Catharanthus roseus plants with very low content. The vincristine contents of four transgenic lines expressing the CrDAT gene are increased from 162.59% to 247.76% compared with the non-transgenic plants 2.3.1.122 trehalose O-mycolyltransferase drug development antigen 85 proteins are potential drug targets 2.3.1.129 acyl-[acyl-carrier-protein]-UDP-N-acetylglucosamine O-acyltransferase drug development the enzyme is a target for design of inhibitors with antibiotic potency 2.3.1.129 acyl-[acyl-carrier-protein]-UDP-N-acetylglucosamine O-acyltransferase drug development development of small molecule, dual-binding LpxA/LpxD inhibitors as novel antimicrobials 2.3.1.129 acyl-[acyl-carrier-protein]-UDP-N-acetylglucosamine O-acyltransferase drug development LpxA is a potential target for antibacterial drug discovery 2.3.1.129 acyl-[acyl-carrier-protein]-UDP-N-acetylglucosamine O-acyltransferase drug development Lpxa is a viable target for antimicrobial drug development 2.3.1.157 glucosamine-1-phosphate N-acetyltransferase drug development due to developed resistance against the existing anti-tubercular drugs by Mycobacteriumm tuberculosis, the enzyme is a target for drug development. Targeting uridyltranferase activity of Mtu GlmU would be a better choice for therapeutic intervention, since at low metabolite concentrations, inhibition of either of the GlmU reactions cause significant decrement in the overall GlmU rate, but at higher metabolite concentrations, uridyltransferase inhibition shows higher decrement, overview 2.3.1.157 glucosamine-1-phosphate N-acetyltransferase drug development GlmU is a target for drug development against Mycobacteria 2.3.1.157 glucosamine-1-phosphate N-acetyltransferase drug development GlmU is a target for inhibitor design 2.3.1.157 glucosamine-1-phosphate N-acetyltransferase drug development the enzyme is a target for inhibitor development in treatment of tuberculosis 2.3.1.157 glucosamine-1-phosphate N-acetyltransferase drug development the enzyme GlmU is a target for development of antibacterial drugs 2.3.1.176 propanoyl-CoA C-acyltransferase drug development targeting insect SCP-2 may be a viable approach for the development of insecticides 2.3.1.179 beta-ketoacyl-[acyl-carrier-protein] synthase II drug development the enzyme is a target for antibacterial drugs 2.3.1.179 beta-ketoacyl-[acyl-carrier-protein] synthase II drug development fatty acid synthesis type II system enzymes are essential for bacterial membrane lipid biosynthesis and represent increasingly promising targets for the discovery of antibacterial agents with different mechanisms of action 2.3.1.179 beta-ketoacyl-[acyl-carrier-protein] synthase II drug development the enzyme is a promising target for the development of therapeutic agents 2.3.1.179 beta-ketoacyl-[acyl-carrier-protein] synthase II drug development the enzyme is an antibiotic target in Gram-positive bacteria and might also be a target in Gram-negative bacteria 2.3.1.180 beta-ketoacyl-[acyl-carrier-protein] synthase III drug development the enzyme represents a target for structure-based design of antimycobacterial agents 2.3.1.180 beta-ketoacyl-[acyl-carrier-protein] synthase III drug development the highly conserved enzyme is an attractive target for antimicrobial inhibitor design 2.3.1.180 beta-ketoacyl-[acyl-carrier-protein] synthase III drug development the enzyme is a target for inhibitor development 2.3.1.180 beta-ketoacyl-[acyl-carrier-protein] synthase III drug development FabH is a particularly attractive target for design of antibacterial agents since it is central to the initiation of fatty acid biosynthesis and is highly conserved among Gram positive and negative bacteria 2.3.1.180 beta-ketoacyl-[acyl-carrier-protein] synthase III drug development FabH is an attractive target for the development of antibacterial agents 2.3.1.180 beta-ketoacyl-[acyl-carrier-protein] synthase III drug development the enzyme is a target for antiparasite inhibitors 2.3.1.180 beta-ketoacyl-[acyl-carrier-protein] synthase III drug development beta-ketoacyl-ACP-synthase III (FabH or KAS III) has become an attractive target for the development of antibacterial agents which can overcome the multidrug resistance 2.3.1.180 beta-ketoacyl-[acyl-carrier-protein] synthase III drug development the enzyme is a potential target for anti-infection drug discovery, the dimer interface in FabH is potentially a viable target for designing another class of inhibitors 2.3.1.180 beta-ketoacyl-[acyl-carrier-protein] synthase III drug development the enzyme is a promising target for the development of therapeutic agents 2.3.1.184 acyl-homoserine-lactone synthase drug development synthetic inhibitors of acyl-HSL synthases might be useful therapeutically for controlling pathogens 2.3.1.191 UDP-3-O-(3-hydroxyacyl)glucosamine N-acyltransferase drug development LpxD is a viable target for antimicrobial development 2.3.1.203 UDP-N-acetylbacillosamine N-acetyltransferase drug development development of a new series of thienopyrimidine-6-carboxylate inhibitors of the Campylobacter jejuni PglD UDP-amino-sugar acetyltransferase enzyme, which upon further optimization may lead to new agents with targeted antivirulence activity 2.3.1.209 dTDP-4-amino-4,6-dideoxy-D-glucose acyltransferase drug development the enzyme might be a valuable source for the production of dTDP-D-Qui4N and dTDP-D-Qui4NAc, which are potentially useful in the pharmaceutical industry for drug development 2.3.1.230 2-heptyl-4(1H)-quinolone synthase drug development the enzyme PqsBC is a potential drug target 2.3.1.241 Kdo2-lipid IVA acyltransferase drug development LpxL2 might be a candidate target in the development of anti-Klebsiella pneumoniae drugs 2.3.1.243 acyl-Kdo2-lipid IVA acyltransferase drug development mutants deleted either for the Braun lipoprotein genes lppA and lppB or in combination with the msbB gene, which encodes an acetyltransferase required for lipid A modification of lipopolysaccharide provided complete protection to immunized mice against a lethal oral challenge dose of wild type Salmonella typhimurium. These mutants may serve as excellent vaccine candidates and also provide a platform for delivering heterologous antigens 2.3.1.250 [Wnt protein] O-palmitoleoyl transferase drug development PORCN is a prominent target for developing inhibitors for various cancers 2.3.1.262 anthraniloyl-CoA anthraniloyltransferase drug development antivirulence concepts through the inhibition of PqsD in the treatment of bacterial infections 2.3.1.294 meromycolic acid 3-oxoacyl-(acyl carrier protein) synthase II drug development the enzyme, along with the other enzyme involved in the FAS-II complex, is a potential target for development of anti-tubercular drugs 2.3.2.2 gamma-glutamyltransferase drug development development of 5-thiohistidine derivatives as therapeutics for GGT-positive tumors 2.3.2.5 glutaminyl-peptide cyclotransferase drug development QCT would be suitable for enzyme therapy in gluten intolerance and appear to have synergistic action with porcine intestinal extracts, potential for enzyme therapy in coeliac disease 2.3.2.5 glutaminyl-peptide cyclotransferase drug development development of hQC enzyme inhibitors, 5,6-dimethoxy-N-(3-(5-methyl-1H-imidazol-1-yl)propyl)-1Hbenzo[d]imidazol-2-amine is a potential drug for treatment of Alzheimer's disease 2.3.2.5 glutaminyl-peptide cyclotransferase drug development development of small molecule inhibitors of glutaminyl cyclase and isoglutaminyl cyclase for Alzheimers disease 2.3.2.5 glutaminyl-peptide cyclotransferase drug development glutaminyl cyclase is a drug target to diminish pE-Abeta formation 2.3.2.5 glutaminyl-peptide cyclotransferase drug development the enzyme is a potential target for the development of novel anti-Alzheimer disease agents. Phenol-40 (R1-), C5-OH (R2-) and C7-OH (R3-) modified apigenin derivatives are synthesized and evaluated as another class of human QC (hQC) inhibitors 2.3.2.23 E2 ubiquitin-conjugating enzyme drug development UbcA1 shows antitumor properties, a potential anticancer drug candidate 2.3.2.23 E2 ubiquitin-conjugating enzyme drug development enzyme Ube2T represents an attractive target for the development of inhibitors. Modulation of DNA repair pathways is a strategy for the development of inhibitors of tumor cell growth, as it can either potentiate the effects of radiotherapy and conventional genotoxins or exploit synthetic lethal interactions 2.3.2.24 (E3-independent) E2 ubiquitin-conjugating enzyme drug development E2 ubiquitin-conjugating enzymes might be potential drug targets, potential strategies for drug discovery targeting UBE2O, overview 2.3.3.5 2-methylcitrate synthase drug development androstenedione is an important steroid medicine intermediate that is obtained via the degradation of phytosterols by mycobacteria. The production process of androstenedione is mainly the degradation of the phytosterol aliphatic side chain, which is accompanied by the production of propionyl CoA. Excessive accumulation of intracellular propionyl-CoA produces a toxic effect in mycobacteria, which restricts the improvement of production efficiency. Biotransformation at low nitrogen levels can be improved by enhancing the methylcitrate cycle with transcriptional regulators PrpR and GlnR of Mycobacterium neoaurum 2.3.3.5 2-methylcitrate synthase drug development the fungi-specific 2-methylcitrate cycle is responsible for detoxifying propionyl-CoA, a toxic metabolite produced as the fungus breaks down proteins and amino acids. The enzyme responsible for this detoxification is 2-methylcitrate synthase (mcsA) and is a potential candidate for the design of new anti-fungals 2.3.3.8 ATP citrate synthase drug development Mendelian randomization of large human cohorts has validated ACLY as a promising target for low-density-lipoprotein-cholesterol lowering and cardiovascular protection 2.3.3.8 ATP citrate synthase drug development the dysfunction and upregulation of ATP citrate lyase in numerous cancers makes it an attractive target for developing anticancer therapies. ATP citrate lyase inhibition by shRNA knockdown limits cancer cell proliferation and reduces cancer stemness 2.3.3.8 ATP citrate synthase drug development the enzyme is a target for anticancer drugs, because many cancer cells depend on its activity for proliferation. ACLY is also a target against dyslipidaemia and hepatic steatosis. Under physiological conditions, citrate carries three negative charges and establishes predominantly hydrophilic and ionic interactions with the enzyme in its binding site, which would not be optimal for drug discovery. The extensive conformational changes observed here reveal a hydrophobic cavity in the core of the citrate domain allowing the high-affinity binding of more hydrophobic and drug-like molecules such as NDI-091143. The allosteric site offers an attractive target for the development of ACLY inhibitors 2.3.3.13 2-isopropylmalate synthase drug development the enzyme is required for the proliferation of Mycobacterium tuberculosis and is also indispensable for its survival during the latent phase of infection. It is absent in humans and is widely regarded as one of the validated drug targets against Tuberculosis 2.4.1.1 glycogen phosphorylase drug development glycogen phosphorylase is an active target of research in search of inhibitors for the treatment of type II diabetes 2.4.1.1 glycogen phosphorylase drug development pentacyclic triterpenes, as inhibitors of glycogen phosphorylase, hold promise for the treatment of type-2 diabetes and other diseases with disorders in glycogen metabolism 2.4.1.1 glycogen phosphorylase drug development the enzyme is a target for inhibitor design in development of drugs for treatment of type 2 diabetes 2.4.1.1 glycogen phosphorylase drug development the enzyme glycogen phosphorylase constitutes an adequate pharmacological target to modulate cellular glycogen levels, by means of inhibition of its catalytic activity 2.4.1.1 glycogen phosphorylase drug development the enzyme is an important target for is a validated target for the development of type 2 diabetes treatments and the discovery of hypoglycaemic agents, both synthetic and natural 2.4.1.4 amylosucrase drug development amylosucrase has great potential in the biotechnology and food industries, due to its multifunctional enzyme activities. It can synthesize alpha-1,4-glucans, like amylose, from sucrose as a sole substrate. It can also utilize various other molecules as acceptors. In addition, amylosucrase produces sucrose isomers such as turanose and trehalulose. It also efficiently synthesizes modified starch with increased ratios of slow digestive starch and resistant starch, and glucosylated functional compounds with increased water solubility and stability. It produces turnaose more efficiently than other carbohydrate-active enzymes. Amylose synthesized by amylosucrase forms microparticles and these can be utilized as biocompatible materials with various bio-applications, including drug delivery, chromatography, and bioanalytical sciences 2.4.1.15 alpha,alpha-trehalose-phosphate synthase (UDP-forming) drug development TPS is a potential insecticidal molecular target, 4-substituted 2,6-diamino-3,5-dicyano-4H-thiopyrans may serve as lead compounds for the development of insecticides with a distinct mode of action 2.4.1.15 alpha,alpha-trehalose-phosphate synthase (UDP-forming) drug development TPS is a potential insecticidal molecular target, 4-substituted 2,6-diamino-3,5-dicyano-4H-thiopyrans may serve as lead compounds in for the development of insecticides with a distinct mode of action 2.4.1.17 glucuronosyltransferase drug development drug development process aims to produce safe, effective drugs within a reasonable time and at a reasonable cost. Phase II metabolism (glucuronidation) can affect drug action and pharmacokinetics to a considerable extent. Extensive glucuronidation is an obstacle to oral bioavailability because the first-pass glucuronidation or premature clearance by UDP-glucuronosyltransferases of orally administered agents frequently results in poor oral bioavailability and lack of efficacy. Modeling of chemical entities/drugs for UGTs and their kinetic data can be useful in understanding the binding patterns to be used in the design of better molecules, analysis of first-pass glucuronidation by intestinal UGTs, including their topology, expression profile, and pharmacogenomics, and substrate selectivity at the binding pocket, structural requirements, and mechanism of enzyme actions, detailed overview 2.4.1.18 1,4-alpha-glucan branching enzyme drug development small molecules with diverse scaffolds but similar three-dimensional structures show a similar biological effect. Deriving scaffolds from docking and similarity search is a successful design strategy for difficult targets 2.4.1.38 beta-N-acetylglucosaminylglycopeptide beta-1,4-galactosyltransferase drug development the enzyme is a target enzyme for drug design 2.4.1.38 beta-N-acetylglucosaminylglycopeptide beta-1,4-galactosyltransferase drug development the enzyme is a target for rational design of specific inhibitors 2.4.1.41 polypeptide N-acetylgalactosaminyltransferase drug development further studies of the substrate specificity of these and potentially additional enzymes are required, but it may be anticipated that this understanding will be significant for insight into O-glycosylation processing and of practical use, for example, for designing appropriate mammalian expression systems for recombinant glycoproteins in drug use 2.4.1.41 polypeptide N-acetylgalactosaminyltransferase drug development further studies of the substrate specificity of these and potentially additional enzymes are required, but it may be anticipated that this understanding will be significant for our insight into O-glycosylation processing and of practical use, for example, for designing appropriate mammalian expression systems for recombinant glycoproteins in drug use 2.4.1.80 ceramide glucosyltransferase drug development the enzyme is an attractive target for drug development both in relation to lysosomal storage disorders (in particular Gaucher disease) and type2 diabetes 2.4.1.83 dolichyl-phosphate beta-D-mannosyltransferase drug development inhibition of DPMS is a promising strategy for the development of anti-trypanosomal agents. Thiazolidinones [(5Z)-5-[[4-(benzyloxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid, [(5Z)-5-[[3,4-bis(benzyloxy)phenyl]methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid and [(5Z)-5-[(2-hydroxyphenyl)methylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid in particular are promising candidates for further development because of their respective activities against trypanosomal DPMS and GPI anchor biosynthesis 2.4.1.129 peptidoglycan glycosyltransferase drug development the essential function of the enzyme makes it an attractive antimicrobial target 2.4.1.129 peptidoglycan glycosyltransferase drug development peptidoglycan glycosyltransferase (PGT) is regarded as a potential drug target for development of antibiotics 2.4.1.133 xylosylprotein 4-beta-galactosyltransferase drug development the enzyme is a target for the development of enzyme inhibitors as regulators of glycosaminoglycan synthesis in therapeutics 2.4.1.140 alternansucrase drug development formation of oligosaccharides by alternansucrase may serve as prebiotics 2.4.1.152 4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase drug development development of a high-throughput screening system for identification of FucT-VII inhibitors, which could have anti-inflammatory or anti-metastatic potential, utilizing scintillation proximity assay with fetuin-coated beads, overview 2.4.1.152 4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase drug development fucosyltransferase VII is a very promising drug target for treatment of inflammatory skin diseases 2.4.1.152 4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase drug development FucT-VII and the E- and P-selectin pathways may prove a fruitful therapeutic target in the prevention or treatment of atherosclerosis 2.4.1.155 alpha-1,6-mannosyl-glycoprotein 6-beta-N-acetylglucosaminyltransferase drug development COS may serve as a potential therapeutic candidate for the treatment of metastatic breast cancer 2.4.1.170 isoflavone 7-O-glucosyltransferase drug development isoflavonoids and their glycosides may prove useful as anticancer drugs with added advantage of increased solubility, stability and bioavailability. Among the six compounds tested, genistein most effectively inhibits the growth of B16F10 and AGS cells, with IC50 values of 0.0077 mM and 0.0398 mM, respectively. Unlike derivatives of genistein (genistin and biochanin A), the glycosylated and methylated forms of daidzein (daidzin and formononetin) exhibit more effective growth inhibition than aglycon, daidzein 2.4.1.174 glucuronylgalactosylproteoglycan 4-beta-N-acetylgalactosaminyltransferase drug development functional link of oncofetal chondroitin sulfate glycosaminoglycan chains (ofCS) modifications with cancer cell motility, chondroitin sulfate synthesis knockdown is a therapeutic cancer target 2.4.1.174 glucuronylgalactosylproteoglycan 4-beta-N-acetylgalactosaminyltransferase drug development the enzyme is an anti-HCV target to combat drug resistance. Cajanine derivatives are a class of anti-HCV agents downregulating the enzyme 2.4.1.212 hyaluronan synthase drug development inhibition of hyaluronan synthase 3-dependent synthesis of hyaluronan dampens systemic Th1 cell polarization and reduces plaque inflammation. Hyaluronan synthase 3 might be a promising therapeutic target in atherosclerosis. Because hyaluronan synthase 3 is regulated by IL-1beta, therapeutic anti-IL-1beta antibodies, may exert their beneficial effects on inflammation in post-myocardial infarction patients in part via effects on hyaluronan synthase 3 2.4.1.212 hyaluronan synthase drug development the enzyme actively synthesizes hyaluronan in hepatic stellate cells and promotes hepatic stellate cells activation and liver fibrosis through Notch1. Targeted hyaluronan inhibition may have potential to be an effective therapy for liver fibrosis 2.4.1.214 glycoprotein 3-alpha-L-fucosyltransferase drug development RNA interference technology obtains a targeted down-regulation of the endogenous beta1,2-xylosyltransferase (XylT) and alpha1,3-fucosyltransferase (FucT) genes, whereby generating RNAi lines which are stable, viable and do not show any obvious phenotype, thus providing a robust tool for the production of therapeutically relevant glycoproteins in plants with a humanized N -glycan structure 2.4.1.221 peptide-O-fucosyltransferase drug development POFUT1 is a potential target for cancers driven by Notch1 mutations 2.4.1.227 undecaprenyldiphospho-muramoylpentapeptide beta-N-acetylglucosaminyltransferase drug development MurG is a target for development of antibacterial agents 2.4.1.227 undecaprenyldiphospho-muramoylpentapeptide beta-N-acetylglucosaminyltransferase drug development MurG is a target for drug development to treat diseases caused by Clostridium difficile, an etiologic agent of a variety of gastrointestinal diseases in humans including mild sporadic diarrhea and severe life-threatening pseudomembranous colitis 2.4.1.227 undecaprenyldiphospho-muramoylpentapeptide beta-N-acetylglucosaminyltransferase drug development the enzyme is an important and unique drug target in Acinetobacter baumannii since it plays a key role during the synthesis of peptidoglycan and it is not found in Homo sapiens. In-silico based exploring of potential lead candidates from the library of natural products for the treatment of Acinetobacter baumannii infections is accomplished with the aid of systematic computational analysis. A 3D model of MurG is predicted using comparative protein modeling approach based on homologous MurG structure from Escherichia coli (strain K12) (PDB ID: 1F0K). Concordance binding site analysis is performed to identify the putative ligand binding sites of optimized MurG model for virtual screening and docking studies against natural compounds subset of Zinc database 2.4.1.232 initiation-specific alpha-1,6-mannosyltransferase drug development along with the possibility of a lack of the immunogenic terminal alpha-1,3-mannose linkages in Yarrowia lipolytica, a Yloch1delta mutant strain can be exploited as a platform strain for developing another potential yeast system that can produce recombinant glycoproteins with human-compatible oligosaccharides 2.4.1.289 N-acetylglucosaminyl-diphospho-decaprenol L-rhamnosyltransferase drug development WbbL is a good target for the development of antituberculosis therapeutics 2.4.2.1 purine-nucleoside phosphorylase drug development the enzyme is a target for drug development 2.4.2.1 purine-nucleoside phosphorylase drug development differences in specificity between homotrimeric (including human enzyme) and homohexameric PNPs, including various pathogenic organisms, make them interesting potential drug targets 2.4.2.1 purine-nucleoside phosphorylase drug development owing to their key role in the purine salvage pathway, PNPs are attractive targets for drug design against some pathogens 2.4.2.1 purine-nucleoside phosphorylase drug development Plasmodium falciparum purine nucleoside phosphorylase (PfPNP) can be targeted for antimalarial drug design since its inhibition kills malaria parasites both in vitro and in vivo 2.4.2.1 purine-nucleoside phosphorylase drug development the enzyme is a target for development of anti-malarial drugs 2.4.2.3 uridine phosphorylase drug development UP12 is a target for development of enzyme inhibitors for cancer chemotherapy, design of inhibitors is intended to boost endogenous uridine levels to rescue normal tissues from the toxicity of fluoropyrimidine nucleoside chemotherapeutic agents, such as capecitabine and 5-fluorouracil. 2.4.2.7 adenine phosphoribosyltransferase drug development the enzyme is a target for antileishmanicidal drug development 2.4.2.8 hypoxanthine phosphoribosyltransferase drug development the enzyme is a target for antimalarial inhibitor design and development 2.4.2.8 hypoxanthine phosphoribosyltransferase drug development hypoxanthine-guanine phosphoribosyltransferase is an excellent target for antimalarial drug discovery 2.4.2.8 hypoxanthine phosphoribosyltransferase drug development structural differences between the Tbr and human enzymes suggest that selective inhibitors for the Tbr enzyme can be designed. Crystal structures of the enzyme in complex with GMP and IMP and with three acyclic nucleoside phosphonate (ANP) inhibitors are determined. Differences occur between the diphosphate binding loops in human HGPRT and TbrHGPRT 2.4.2.8 hypoxanthine phosphoribosyltransferase drug development the enzyme is a possible target for anti-parasite drug development 2.4.2.8 hypoxanthine phosphoribosyltransferase drug development the hypoxanthineguanine phosphoribosyltransferase (HGPRT) represents a potential target for specific inhibitor development 2.4.2.12 nicotinamide phosphoribosyltransferase drug development inhibitor-soaking experiments 2.4.2.17 ATP phosphoribosyltransferase drug development HisG represents a potential drug target for tuberculosis 2.4.2.28 S-methyl-5'-thioadenosine phosphorylase drug development combination of 5'-methylthioadenosine with clinical cancer drugs 5-fluorouracil or 6-thioguanine, in the treatment of MTAP-negative tumors, may produce a significantly improved therapeutic index 2.4.2.28 S-methyl-5'-thioadenosine phosphorylase drug development loss of MTAP activity in a subset of chordomas suggests that this group of patients may benefit from chemoselective inhibition of the de novo purine synthesis pathway. Purine synthesis inhibitors may be considered for chordoma patients with MTAP-deficient tumours 2.4.2.28 S-methyl-5'-thioadenosine phosphorylase drug development potential of MTAN as target for bacterial anti-infective drug design 2.4.2.30 NAD+ ADP-ribosyltransferase drug development the enzyme can be a target for anti-bacterial treatment 2.4.2.36 NAD+-diphthamide ADP-ribosyltransferase drug development more potent therapeutics for treatment of bacterial diseases and infections through understanding of ADPRT reaction meachanism 2.4.3.4 beta-galactoside alpha-2,3-sialyltransferase drug development ST3Gal III can serve as a therapeutic target of taxol therapy 2.4.3.8 alpha-N-acetylneuraminate alpha-2,8-sialyltransferase drug development basis for design of sialyltransferase-specific drugs 2.4.3.8 alpha-N-acetylneuraminate alpha-2,8-sialyltransferase drug development the enzyme can serve as a potential druggable target for inhibiting tumor initiation and metastasis. GD3S expression correlates with activation of the c-Met signaling pathway leading to increased stem cell properties and metastatic competence, the GD3S-c-Met axis might serve as an effective target for the treatment of metastatic breast cancers 2.4.99.16 starch synthase (maltosyl-transferring) drug development a coumarin-based Cu(II)-mDPA sensor (Cu-1b) is developed using internal charge transfer as the sensing mechanism for the selective detection of phosphate ions in HEPES buffer with an association constant of 140000/M. The Cu(II)-di(methylpyridylmethyl)amine-coumarin sensor acts as a robust and sensitive sensor to probe the enzyme-catalyzed reaction. This fluorescence turn-on assay may facilitate the screening of GlgE inhibitors for the discovery of new anti-tuberculosis drugs 2.4.99.18 dolichyl-diphosphooligosaccharide-protein glycotransferase drug development cryoelectron microscopy structures of human oligosaccharyltransferase complexes OST-A and OST-B provide a basis for the design of inhibitors of N-glycosylation that modulate the maturation and activation of protein markers involved in tumor formation 2.4.99.23 lipopolysaccharide heptosyltransferase I drug development heptosyltransferase I (WaaC) is an integral part in the concept of antivirulence to combat increasing bacterial antibiotic resistance 2.5.1.6 methionine adenosyltransferase drug development the enzyme form has a less extensive subunit interface than some previously determined structures, and contains some key structural differences from the human enzyme in an allosteric site, presenting an opportunity for the design of selective inhibitors against the S-adenosylmethionine synthetase from this organism 2.5.1.6 methionine adenosyltransferase drug development the product S-adenosyl-L-methionine is an effective cure for liver disease, depressive syndromes, and osteoarthritis. A multiple-copy integrative plasmid pYMIKP-SAM2 is introduced into the chromosome of wild-type Saccharomyces cerevisiae strain ZJU001 to construct the recombined strain R1-ZJU001. The recombinant yeast exhibits higher enzymatic activity of methionine adenosyltransferase and improved S-adenosyl-L-methionine biosynthesis. With a three-phase fed-batch strategy in 15-liter bench-top fermentor, 8.81 g/l S-adenosyl-L-methionine is achieved after 52 h cultivation of R1-ZJU001, about 27.1 % increase over its parent strain ZJU001, whereas the S-adenosyl-L-methionine content is also improved from 64.6 mg/g dry cell weight to 91.0 mg/g dry cell weight 2.5.1.7 UDP-N-acetylglucosamine 1-carboxyvinyltransferase drug development cell-wall synthesis is an important target for antibacterial agents, and MurA is one of the few enzymes involved in the cytoplasmic stage of peptidoglycan biosynthesis which is specifically inhibited by an existing antimicrobial agent 2.5.1.7 UDP-N-acetylglucosamine 1-carboxyvinyltransferase drug development enzyme is an ideal target for the discovery of novel antibiotics against gram-negative pathogens as they have only one copy of murA gene in its genome 2.5.1.7 UDP-N-acetylglucosamine 1-carboxyvinyltransferase drug development MurA will be a useful target to identify potential inhibitors of fosfomycin resistance in pharmacological studies 2.5.1.9 riboflavin synthase drug development riboflavin synthase is a target for the design of potential antibiotics 2.5.1.10 (2E,6E)-farnesyl diphosphate synthase drug development the discovery of new binding sites and non-bisphosphonate binders is a critical step towards the investigation of farnesyl pyrophosphate synthase as a drug target for human African trypanosomiasis and opens up the possibility of a fragment-to-lead optimisation program 2.5.1.15 dihydropteroate synthase drug development cannot bypass DHPS activity during inhibition of the functional ortholog MtDHPS (folP1) as treatment of tuberculosis 2.5.1.15 dihydropteroate synthase drug development lead compound for design of antimicrobacterial inhibitors 2.5.1.15 dihydropteroate synthase drug development target in treatment of tuberculosis 2.5.1.15 dihydropteroate synthase drug development targeting approach of the dihydropteroate synthase enzyme, which serves as the site of action for the sulfonamide class of antimicrobial agents, exploring a class of transition state mimics, that can bind to the pterin, phosphate and para-amino binding sites, as trivalent inhibitors, binding modeling, overview 2.5.1.16 spermidine synthase drug development the enzyme is a drug target in the malaria parasite, Plasmodium falciparum, due to the vital role of spermidine in the activation of the eukaryotic translation initiation factor and cell proliferation 2.5.1.18 glutathione transferase drug development the enzyme is a target for inhibitor design 2.5.1.18 glutathione transferase drug development the enzyme is a target for development of irreversible GST inhibitors as anticancer agents based on prostaglandins 2.5.1.18 glutathione transferase drug development the enzyme is a target for drug development against the parasite 2.5.1.18 glutathione transferase drug development the enzyme is a target for structure-based drug/inhibitor design 2.5.1.18 glutathione transferase drug development glutathione S-transferases of Plasmodium parasites are potential targets for antimalarial drug and vaccine development 2.5.1.19 3-phosphoshikimate 1-carboxyvinyltransferase drug development differential inhibition of class I and class II EPSPS by tetrahedral reaction intermediate-analogues possibly due to alteration of open-close transition during catalysis and/or upon inhibitor binding but not due to energy differences during complex formation 2.5.1.19 3-phosphoshikimate 1-carboxyvinyltransferase drug development more experimental data needed for effective structure-based drug design 2.5.1.19 3-phosphoshikimate 1-carboxyvinyltransferase drug development protonated enolpyruvylshikimate 3-phosphate (cation) intermediate as potential target for inhibitor design 2.5.1.21 squalene synthase drug development LdSSN is a potential drug target for visceral leishmaniasis 2.5.1.21 squalene synthase drug development enzyme SQS is a potential target for antiviral strategies against hepatitis C virus 2.5.1.21 squalene synthase drug development the enzyme is a target for development of next-generation hypocholesterolemia drugs 2.5.1.29 geranylgeranyl diphosphate synthase drug development validation of GGDPS as a therapeutic target and assesses the advantages of targeting GGDPS relative to other enzymes involved in geranylgeranylation. Compounds that directly inhibit geranylgeranyl diphosphate synthesis may also display therapeutic efficacy in bone diseases, with potential to decrease side effects unrelated to the mechanism 2.5.1.29 geranylgeranyl diphosphate synthase drug development the enzyme possibly represents an attractive drug target for the development of selective inhibitors aiming the erythrocytic stages of Plasmodium falciparum and development of more potent bisphosphonate-based inhibitors selectivity targeting this key point of the plasmodial isoprenoid metabolism 2.5.1.31 ditrans,polycis-undecaprenyl-diphosphate synthase [(2E,6E)-farnesyl-diphosphate specific] drug development enzyme UppS is an attractive antibacterial target, but incomplete inhibition of UppS function may lead to increased resistance to some cell wall-active antibiotics 2.5.1.46 deoxyhypusine synthase drug development fungal DHS is a target for the development of inhibitors, for which CNI-1493 may serve as a lead substance 2.5.1.46 deoxyhypusine synthase drug development Cryptosporidium parvum DHS is a traget for drug development, as GC7 effectively inhibits parasite infection and growth in cultured host cells 2.5.1.47 cysteine synthase drug development cysteine biosynthetic pathway is absent in humans but essential in microbial pathogens, suggesting that it provides potential targets for the development of novel antibacterial compounds 2.5.1.47 cysteine synthase drug development cysteine synthase is a potential drug target for trichomoniasis 2.5.1.47 cysteine synthase drug development O-acetyl-L-serine sulfhydrylase is a promising target for inhibiting the growth of Entamoeba histolytica 2.5.1.47 cysteine synthase drug development since mammals lack OASS, the enzyme is a potential target for antimicrobial agents 2.5.1.47 cysteine synthase drug development the enzyme is a rational drug target against amebiasis 2.5.1.58 protein farnesyltransferase drug development the enzyme from Aspergillus fumigatus is a target for antifungal drug design 2.5.1.72 quinolinate synthase drug development te enzyme is required for the biosynthesis of NAD. Besides the de novo pathway for NAD synthesis, a salvage pathway exists in some organisms allowing NAD to be recycled from nicotinic acid and nicotinamide. Some pathogens such as Mycobacterium leprae and Helicobacter pylori lack this salvage pathway. The different pathways for quinolinate biosynthesis in most prokaryotes and eukaryotes, combined with the fact that the salvage pathway is absent in some pathogenic microorganisms, make enzyme NadA an ideal target in the search for specific antibacterial drugs 2.5.1.78 6,7-dimethyl-8-ribityllumazine synthase drug development the enzyme is a potential drug target for the development of broad-spectrum antifungal drugs 2.5.1.80 7-dimethylallyltryptophan synthase drug development 7-DMATS catalyzes regio- and stereospecific prenylations and can be used as efficient catalysts for chemoenzymatic synthesis of prenylated compounds, which can be then tested for their biological activities in drug discovery and development programs 2.5.1.86 trans,polycis-decaprenyl diphosphate synthase drug development the enzyme is a target for development of specific inhibitors for anti-infective therapies that block virulence factor formation, the enzyme is a target in treatment of tuberculosis 2.5.1.92 (2Z,6Z)-farnesyl diphosphate synthase drug development the enzyme possibly represents an attractive drug target for the development of selective inhibitors aiming the erythrocytic stages of Plasmodium falciparum and development of more potent bisphosphonate-based inhibitors selectivity targeting this key point of the plasmodial isoprenoid metabolism 2.6.1.13 ornithine aminotransferase drug development human OAT as a potential target for development of new therapeutic drugs, OAT holds a significant scientific interest because of its association with gyrate atrophy, a recessive hereditary genetic dissorder leading to progressive loss of vision and eventually blindness in humans 2.6.1.13 ornithine aminotransferase drug development human OAT is recognized as a potential target for chemotherapeutic drug development, in a study performed to evaluate the effect of selective blocking of mitosis in human cancer cells, OAT is identified as a protein, which binds the antimitotic drug diazonamide A and it has a role in regulating mitotic cell division 2.6.1.13 ornithine aminotransferase drug development because TgOAT possesses parasite-specific structural features as well as differing substrate specificity from its human homologue, it is an attractive target for anti-toxoplasmosis inhibitor design that can be exploited for chemotherapeutic intervention 2.6.1.42 branched-chain-amino-acid transaminase drug development the enzyme mutant BCAT2 T186R is a precision drug target in glioblastoma (GBM) 2.6.1.83 LL-diaminopimelate aminotransferase drug development the enzyme is a target for drug development 2.6.1.83 LL-diaminopimelate aminotransferase drug development the LL-diaminopimelate aminotransferase (DapL) pathway is an attractive pipeline to identify targets for the development of antibiotic compounds 2.7.1.26 riboflavin kinase drug development HsRFK parameters differ from those of the so far evaluated bacterial counterparts, suggesting species-specific mechanisms in RFK catalysis. Thus, HsRFK is a potential therapeutic target because of its key functions, while bacterial RFK modules are potential antimicrobial targets 2.7.1.30 glycerol kinase drug development glycerol kinase 5 (GK5) is a potential therapeutic target for treatment of NSCLC with resistance to EGFR tyrosine kinase inhibitors 2.7.1.32 choline kinase drug development choline kinase is elevated in cancer cells and presents a novel target for increasing cell kill. Data support exploring transient Chk silencing as a broad-spectrum chemotherapeutic agent for cancer cells. 2.7.1.32 choline kinase drug development choline kinase is gaining importance as a potential target for anticancer therapy 2.7.1.32 choline kinase drug development target for therapy since its specific inhibitors display efficient antitumoral activity in vivo 2.7.1.32 choline kinase drug development choline kinase is a promising target for development of inhibitors and inhibition of tumor growth 2.7.1.32 choline kinase drug development targeting the parasite lipid metabolism and choline kinase for pharmacological action constitutes an effective way of dealing with the spreading of the disease and with conventional therapy-resistant strains 2.7.1.33 pantothenate kinase drug development since Entamoeba histolytica PanK (EhPanK) is physiologically important and sufficiently divergent from its human orthologs, this enzyme represents an attractive target for the development of novel anti-amebic chemotherapies 2.7.1.35 pyridoxal kinase drug development in silico analysis of the human and parasite PdxK structure reveals significant differences in the active site region thus highlighting the potential of the parasite PdxK as an antileishmanial drug target 2.7.1.39 homoserine kinase drug development molecular modeling and simulation study of homoserine kinase as an effective leishmanial drug target 2.7.1.40 pyruvate kinase drug development M2-PK is a potential target for tumor therapy, detailed overview 2.7.1.40 pyruvate kinase drug development MRSA PK is a potentially attractive drug target 2.7.1.40 pyruvate kinase drug development the enzyme is a potential target for development of novel antibiotics 2.7.1.40 pyruvate kinase drug development cancer cells rely heavily on PKM2 for anabolic and energy requirements, and specific targeting of PKM2 therefore has potential as strategy for cancer therapy 2.7.1.40 pyruvate kinase drug development human pyruvate kinase muscle isoform 2 is considered an attractive therapeutic target for modulating tumor metabolism. Structure-function analyses of amino acid-mediated PKM2 regulation revealing the chemical requirements in the development of mechanism-based small-molecule modulators targeting the amino acid-binding pocket of PKM2 and provide broader insights into the regulatory mechanisms of complex allosteric enzyme 2.7.1.40 pyruvate kinase drug development structural features of MRSA that are distinct from the human enzyme features makes the Staphylococcus enzyme an antimicrobial target 2.7.1.48 uridine/cytidine kinase drug development RX-3117, an orally available cytidine analogue, is activated by UCK2 which may be used to select patients potentially sensitive to RX-3117 2.7.1.66 undecaprenol kinase drug development the enzyme is a possible anti-cariogenic drug target 2.7.1.67 1-phosphatidylinositol 4-kinase drug development type II phosphatidylinositol 4-kinases are promising targets for therapeutic intervention against viral infections, detailed overview 2.7.1.71 shikimate kinase drug development the enzyme is a target for antimicrobial and anti-paarasite drugs 2.7.1.71 shikimate kinase drug development the enzyme is an attractive drug target 2.7.1.71 shikimate kinase drug development the enzyme is an attractive drug target as it is vital for the survival of Mycobacterium tuberculosis but absent in mammalian hosts 2.7.1.91 sphingosine kinase drug development the enzyme is a potential target for drug discovery 2.7.1.94 acylglycerol kinase drug development the enzyme AGK-based mechanism for constitutive activation of JAK2/STAT3 signaling in solid tumors and may represent a therapeutic target 2.7.1.105 6-phosphofructo-2-kinase drug development isozyme PFKFB4 appears to be a rational target for anti-neoplastic drug development 2.7.1.130 tetraacyldisaccharide 4'-kinase drug development the enzyme structure provides a structural template for designing antibiotics and knowledge of catalysis at the membrane interface 2.7.1.130 tetraacyldisaccharide 4'-kinase drug development several pharmacoinformatics tools such as comparative metabolic pathway analysis (Metacyc), data mining from a database of essential genes (DEG), homology modeling, molecular docking, pharmacophore based virtual screening, ADMET prediction, and molecular dynamics simulation are used to identify the enzyme as a drug target and identify lead compounds against this target 2.7.1.137 phosphatidylinositol 3-kinase drug development the enzyme is a potential target for drug development, e.g. in cancer therapy, analysis of inhibitory potential of LY294002 inhibotr analogues 2.7.1.137 phosphatidylinositol 3-kinase drug development reduction of PI3K/PKCdelta activity represents a therapeutic target to downregulate adhesion molecule L1, CHL1, expression and thus benefit axonal regeneration after spinal cord injury 2.7.1.137 phosphatidylinositol 3-kinase drug development the enzyme is a target for drug design in cancer therapy. Combined targeting of PI3K and mTOR presents an opportunity for robust and synergistic anticancer efficacy 2.7.1.137 phosphatidylinositol 3-kinase drug development the PI3K/Akt signaling pathway is a therapeutic target in treatment of medulloblastoma disease, a primitive neuroectodermal tumor, and the most common malignant pediatric brain tumor 2.7.1.137 phosphatidylinositol 3-kinase drug development the regulatory subunit p55PIK of PI3K is a trget for inhibitor development in cancer therapy 2.7.1.148 4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol kinase drug development enzyme is a target for antimicrobial drug development 2.7.1.148 4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol kinase drug development potential target for anti-infective drugs 2.7.1.148 4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol kinase drug development enzymes of the MEP pathway represent potential targets for the generation of selective antibacterial, antimalarial and herbicidal molecules 2.7.1.150 1-phosphatidylinositol-3-phosphate 5-kinase drug development potential for targeting this kinase in developing small-molecule antivirals against SARS-CoV-2. The infection is fully blocked by bafilomycin A1, which inhibits the vacuolar type H+-ATPase (V-ATPase) acidification activity. Apilimod and vacuolin-1 prevent cytoplasmic entry of VSV-MeGFP-ZEBOV (from Zaire ebolavirus VSV-ZEBOV) 2.7.1.150 1-phosphatidylinositol-3-phosphate 5-kinase drug development the enzyme is a potential target for developing small-molecule antivirals against SARS-CoV-2 2.7.1.154 phosphatidylinositol-4-phosphate 3-kinase drug development PI3KC2alpha may be a suitable drug target for the prevention and treatment of thrombosis and cardiovascular disease 2.7.1.175 maltokinase drug development Mak may be a potential drug target in Mycobacterium tuberculosis 2.7.1.189 autoinducer-2 kinase drug development the enzyme is a target for inhibitor development to establish quorum-sensing inhibition, one of the most promising strategies to face the threat of bacterial resistance 2.7.2.2 carbamate kinase drug development because the L-arginine pathway is essential for Giardia lamblia survival and absent in high eukaryotes including humans, the enzyme is a potential target for drug development 2.7.2.2 carbamate kinase drug development the enzyme is a good drug target and disulfiram may be repurposed as antigiardiasis drug 2.7.3.3 arginine kinase drug development the enzyme could be a useful chemotherapeutic target for the control of cockroach proliferation 2.7.3.4 taurocyamine kinase drug development Schistosoma mansoni is a trematode flatworm that has been identified as the aetiological agent of schistosomiasis, a disease that affects about 200 million people worldwide 2.7.3.9 phosphoenolpyruvate-protein phosphotransferase drug development the enzyme is a target for antibacterial drugs. These drugs can be obtained from peptides or protein fragments able to interfere with the first reaction of the protein cascade: the phosphorylation of the HPr by the first enzyme, the so-called enzyme enzyme I, overview 2.7.3.9 phosphoenolpyruvate-protein phosphotransferase drug development enzyme I, EI, of the phosphoenolpyruvate phosphotransferase system isa drug target to develop antimicrobial agents, xanthone derivatives have high potential to be developed as antibiotics 2.7.4.1 ATP-polyphosphate phosphotransferase drug development enzyme PPK1 is an attractive therapeutic target to control infections caused by multiple drug resistant Pseudomonas aeruginosa 2.7.4.1 ATP-polyphosphate phosphotransferase drug development the enzym eis a target for inhibitor development 2.7.4.1 ATP-polyphosphate phosphotransferase drug development the enzyme might be a potential drug target in bacteria 2.7.4.6 nucleoside-diphosphate kinase drug development the enzyme is a potential target to develop therapeutic approaches to overcome multiresistance of the bacterium against antibiotics 2.7.4.8 guanylate kinase drug development the guanylate-kinase-deficient Escherichia coli strain relies on the presence of a plasmid-borne, functional guanylate kinase for viability. Such a strain will be beneficial to assess the role of specific amino acids of guanylate kinase in structure, function, drug activation, and drug resistance 2.7.4.9 dTMP kinase drug development potential target for antituberculosis drugs 2.7.4.9 dTMP kinase drug development potential target for the development of antituberculosis drugs 2.7.4.9 dTMP kinase drug development potential target for the development of new antituberculosis drugs due to the low sequence similarity with the human enzyme 2.7.4.9 dTMP kinase drug development potential targets for the development of antiviral and cancer therapies 2.7.4.22 UMP kinase drug development as bacterial UMP kinases have no counterpart in eukaryotes, the information provided here can help the design of new antibiotics 2.7.4.22 UMP kinase drug development potential target for antibacterial drugs 2.7.4.22 UMP kinase drug development UMP kinase may be a potential antimicrobial target 2.7.4.22 UMP kinase drug development potential drug target for development of antimicrobial agents, diseases such as urethritis and prostatitis 2.7.4.22 UMP kinase drug development since bacterial UMPKs are specific for the phosphorylation of UMP only and differ from eukaryotic dual-specificity UMP/CMP kinases 2.7.4.22 UMP kinase drug development the enzyme is a potential antibacterial drug target 2.7.4.22 UMP kinase drug development the enzyme is a target for antimicrobial drug development 2.7.4.22 UMP kinase drug development the enzyme is a potential drug target for developing novel anti-tuberculosis drugs 2.7.4.22 UMP kinase drug development the enzyme is found only in bacteria and is a target for the discovery of antibacterials 2.7.6.3 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase drug development the enzyme is a target for antibiotic development 2.7.6.3 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase drug development the enzyme is a target for antimicrobial development 2.7.6.5 GTP diphosphokinase drug development the structural knowledge of the self-regulatory mechanisms for controlling the opposing catalytic activities of RelSeq can be used to design specific inhibitors that interfere with either of the active sites and may have the potential of being developped into powerful antibacterial drugs 2.7.7.1 nicotinamide-nucleotide adenylyltransferase drug development development of NMNATase inhibitors as potential therapeutics against tularemia 2.7.7.3 pantetheine-phosphate adenylyltransferase drug development potential target for antibiotic drugs 2.7.7.3 pantetheine-phosphate adenylyltransferase drug development the enzyme is an attractive target for antibacterial drug development against Helicobacter pylori 2.7.7.6 DNA-directed RNA polymerase drug development development of drugs that target the Pol I transcription machinery at different points for use in cancer therapies, overview 2.7.7.6 DNA-directed RNA polymerase drug development the enzyme is a target for drug design 2.7.7.7 DNA-directed DNA polymerase drug development DNA polymerases are promising drug targets for the treatment of cancer 2.7.7.12 UDP-glucose-hexose-1-phosphate uridylyltransferase drug development the enzyme might be a target for inhibitor design in galactosemia treatment 2.7.7.12 UDP-glucose-hexose-1-phosphate uridylyltransferase drug development Escherichia coli outer membrane vesicles can display the immune protective antigen galactose-1-phosphate uridyltransferase (GalT) of Actinobacillus pleuropneumoniae and confer protection against Actinobacillus pleuropneumoniae virulent strain L20. Outer membrane vesicles can be used as a platform to deliver GalT protein and enhance its immunogenicity to induce both humoral and cellular immune responses in mice 2.7.7.13 mannose-1-phosphate guanylyltransferase drug development the enzyme is a potential target for antimicrobial drug design, i.e. in the treatment of cystic fibrosis caused by Burkholderia cenocepacia 2.7.7.13 mannose-1-phosphate guanylyltransferase drug development the enzyme is a target for inhibitor design for anti-leishmanial therapy 2.7.7.14 ethanolamine-phosphate cytidylyltransferase drug development given the absence of PE synthesis in red blood cells, PfECT represents a potential antimalarial target opening the way for a rational conception of bioactive compounds 2.7.7.18 nicotinate-nucleotide adenylyltransferase drug development the enzyme is a target for inhibitor development 2.7.7.18 nicotinate-nucleotide adenylyltransferase drug development enzyme NadD is a potentially druggable target suitable for the development of selective inhibitors 2.7.7.19 polynucleotide adenylyltransferase drug development polyadenylation inhibition represents one mode of action for 8-chloroadenosine and 8-aminoadenosine in hematological malignancies, among several possible mechanisms. RNA-directed drugs may offer a valuable strategy in targeting indolent cancers, such as multiple myeloma 2.7.7.23 UDP-N-acetylglucosamine diphosphorylase drug development the enzyme is a potential drug target 2.7.7.23 UDP-N-acetylglucosamine diphosphorylase drug development N-acetylglucosamine-1-phosphate uridyltransferase (GlmU) is an attractive target for the development of antimicrobial agents 2.7.7.23 UDP-N-acetylglucosamine diphosphorylase drug development prokaryotic/microbial sugar nucleotidyl transferases are targets for design of selective inhibitors due to their different metal mechanisms compared to eukaryotes 2.7.7.23 UDP-N-acetylglucosamine diphosphorylase drug development the enzyme GlmU is a target for development of antibacterial drugs 2.7.7.23 UDP-N-acetylglucosamine diphosphorylase drug development the enzyme is a target for drugs treating the witches broom disease caused by Moniliophthora perniciosa in Theobroma cacao 2.7.7.23 UDP-N-acetylglucosamine diphosphorylase drug development the identification of a selective inhibitory allosteric binding site in the parasite enzyme and the fact that the human and trypanosome enzymes both display a strictly ordered bi-bi mechanism, but with the order of substrate binding reversed, makes the enzyme a good target for drug development 2.7.7.48 RNA-directed RNA polymerase drug development the enzyme is a target for inhibitor design 2.7.7.48 RNA-directed RNA polymerase drug development the enzyme is a target for drugs in therapy of HCV infection 2.7.7.48 RNA-directed RNA polymerase drug development the functional nature of multimeric arrays of RNA-dependent RNA polymerase supplies a target for antiviral compounds 2.7.7.48 RNA-directed RNA polymerase drug development the virus causes significant economic losses in rabbit farming and reduces wild rabbit populations, and its RNA-dependent RNA polymerase (RdRp) is a primary target for the development of antiviral drugs 2.7.7.49 RNA-directed DNA polymerase drug development the enzyme is a drug target 2.7.7.49 RNA-directed DNA polymerase drug development HIV-1 reverse transcriptase is a major target of antiviral therapy 2.7.7.49 RNA-directed DNA polymerase drug development the enzyme is a primary target in the development of antiviral agents against HIV-1 2.7.7.49 RNA-directed DNA polymerase drug development characterization, and lead optimization of 7-azaindole non-nucleoside HIV-1 reverse transcriptase inhibitors 2.7.7.49 RNA-directed DNA polymerase drug development modeling the functional state of the reverse transcriptase of hepatitis B virus and its application to probing drug-protein interaction 2.7.7.60 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase drug development due to the absence of the pathway in mammals enzyme provides a potential target for new antibiotics 2.7.7.60 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase drug development insights in structure and function of MtIspD 2.7.7.60 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase drug development 2-C-methyl-D-erythritol 4-phosphate cytidyltransferase, enzyme IspD, is a potential therapeutic drug target in Plasmodium vivax 2.7.7.60 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase drug development IspD is a druggable target for the development of additional antimalarial agents. 1R,3S-MMV008138 shows promise as a potential scaffold for target-based antimalarial drug development 2.7.7.60 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase drug development PfIspD enzyme inhibitor MMV008138 does not target the human IspD, reinforcing MMV008138 as a prototype of a distinct class of species-selective IspD-targeting antimalarial agents 2.7.7.60 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase drug development the methyl erythritol phosphate (MEP) pathway, including enzyme MEP cytidylyltransferase (IspD), represents an attractive series of targets for antibiotic design, considering each enzyme of the pathway is both essential and has no human homologues 2.7.7.71 D-glycero-alpha-D-manno-heptose 1-phosphate guanylyltransferase drug development HddC is a potential target of antibiotics against yersiniosis 2.7.7.85 diadenylate cyclase drug development the single enzyme is an attractive target for the development of antibiotic compounds 2.7.7.88 GDP polyribonucleotidyltransferase drug development the large (L) protein of the rabies virus (RABV) is a multifunctional RNA-dependent RNA-polymerase, which is one of the most attractive targets for developing antiviral agents 2.7.7.101 DNA primase DnaG drug development the bacterial primase is a target for antibiotic drugs, inhibitors of DNA primase provide antibiotic agents. Bacterial replisome as a multiple-drug target 2.7.7.101 DNA primase DnaG drug development the DnaG-DnaB interaction is an attractive antibiotic target because it is conserved in bacteria, essential for DNA replication, and is distinctly different from that of viruses, archaea, and eukaryotes 2.7.8.7 holo-[acyl-carrier-protein] synthase drug development the enzyme is a broad-spectrum target for design of antifungal drugs 2.7.8.7 holo-[acyl-carrier-protein] synthase drug development the human pathogen Mycobacterium tuberculosis PPTases are attractive drug targets 2.7.8.13 phospho-N-acetylmuramoyl-pentapeptide-transferase drug development antibacterial chemotherapy against pathogenic bacteria being multiresistant to common antibiotics 2.7.8.13 phospho-N-acetylmuramoyl-pentapeptide-transferase drug development biological activity of uridine moiety in naturally occurring non-specific MraY inhibitors (like liposidomycins and caprazamycins), antibacterial chemotherapy against pathogenic bacteria being multiresistant to common antibiotics 2.7.8.13 phospho-N-acetylmuramoyl-pentapeptide-transferase drug development the specificity of the enzyme to eubacteria makes it a promising potential target to be exploited for antibacterial discovery to combat emerging resistance 2.7.8.B13 phosphatidylinositol phosphate synthase drug development the enzyme is a promising target for the development of anti-mycobacterium drugs 2.7.8.27 sphingomyelin synthase drug development SMS is a target for drug design 2.7.8.27 sphingomyelin synthase drug development enzyme SMS1 is a drug target for the treatment of atherosclerosis 2.7.8.35 UDP-N-acetylglucosamine-decaprenyl-phosphate N-acetylglucosaminephosphotransferase drug development enzyme WecA is a promising target for the development of antituberculous drugs as a countermeasure of drug resistant tuberculosis 2.7.8.35 UDP-N-acetylglucosamine-decaprenyl-phosphate N-acetylglucosaminephosphotransferase drug development the enzyme is a target for development of drugs 2.7.9.1 pyruvate, phosphate dikinase drug development PPDK is a good target in design of antiparasitic agents 2.7.9.1 pyruvate, phosphate dikinase drug development PPDK is not found in vertebrates, so specific inhibitors may be useful for treatment of infections caused by anaerobic protists that depend on pyrophosphate-dependent glycolysis 2.7.9.1 pyruvate, phosphate dikinase drug development the enzyme is a good target for anti-parasite drug design 2.7.9.1 pyruvate, phosphate dikinase drug development the enzyme is a potential herbicide target in C4 plants 2.7.9.1 pyruvate, phosphate dikinase drug development based on its role in the metabolism of microbial human pathogens, PPDK is a potential drug target 2.7.9.2 pyruvate, water dikinase drug development the enzyme is of interest as a target for antibiotic development 2.7.10.1 receptor protein-tyrosine kinase drug development the enzyme is a target for development of anticoccidial agents such as genistein analogues 2.7.10.1 receptor protein-tyrosine kinase drug development aminoquinazoline pyridones are potent, selective, and orally efficacious c-Kit inhibitors for the treatment of fibrotic diseases. Compounds show greater than 200fold selectivity against KDR, p38, Lck, and Src 2.7.10.1 receptor protein-tyrosine kinase drug development genetically altered RTKs and their coupled PI3K/Akt and MAPK pathways may play an extensive role in the tumorigenesis and aggressiveness of anaplastic thyroid cancer, thus specific genotype-based targeting at these signaling pathways may be an effective therapeutic strategy for anaplastic thyroid cancer 2.7.10.1 receptor protein-tyrosine kinase drug development inhibitors of tyrosine kinases, offer the opportunity to reverse chemotherapy resistance and enhance response in patients with localized and advanced breast cancer 2.7.10.1 receptor protein-tyrosine kinase drug development N-alkyl and N-unsubstituted naphthamides are potent and selective inhibitors of KDR 2.7.10.1 receptor protein-tyrosine kinase drug development new series of C-5 substituted indazolylaminoquinazolines as potent ErbB2 kinase inhibitors 2.7.10.1 receptor protein-tyrosine kinase drug development new substance class (4-(indole-3-yl)quinazolines) for the treatment of EGFR-dependent tumors, showing strong fluorescences. No connection between cytotoxicity and EGFR-TK inhibition 2.7.10.1 receptor protein-tyrosine kinase drug development novel series of 4-aminopyrimidine-5-carbaldehyde oximes that are potent and selective inhibitors of both EGFR and ErbB-2 tyrosine kinases 2.7.10.1 receptor protein-tyrosine kinase drug development series of indenopyrazoles designed and synthesized as EGFR tyrosine kinase inhibitors by in silico highthroughput screening 2.7.10.1 receptor protein-tyrosine kinase drug development series of indenopyrazoles designed and synthesized as KDR inhibitors by in silico highthroughput screening 2.7.10.1 receptor protein-tyrosine kinase drug development sorafenib, a multikinase inhibitor of both Raf and VEGF and PDGF receptor tyrosine kinase signaling, inhibits tumor growth and disrupts tumor microvasculature through antiproliferative, antiangiogenic, and/or proapoptotic effects, suggesting its broad preclinical and clinical activity. The inhibitor shows antitumor activity in phase II/III trials involving patients with advanced renal cell carcinoma and hepatocellular carcinoma 2.7.10.1 receptor protein-tyrosine kinase drug development synthesis of a series of naphthyl-based compounds, which are potential inhibitors of vascular endothelial growth factor receptors 2.7.10.1 receptor protein-tyrosine kinase drug development targeting therapy with specific RTK inhibitors may provide benefits for a subgroup of acute myeloid leukemia patients with favorable chromosomes who also carry selective types of RTK mutations. KIT and FLT3 mutations preferentially exist in distinct clinical and genetic acute myeloid leukemia subtypes, reflecting unique leukemogenetic mechanisms 2.7.10.1 receptor protein-tyrosine kinase drug development the restricted, uniform, and constitutive cell surface expression of ROR1 protein in B-CLL provides a strong incentive for the development of targeted therapeutics such as monoclonal antibodies 2.7.10.1 receptor protein-tyrosine kinase drug development treatment of cancer with certain molecularly targeted drugs may have latent effects on testicular development by inhibiting specific physiological signaling pathways (stem cell factor/c-kit and platelet-derived growth factor signaling pathways), which must be taken into consideration, when new molecularly designed cancer therapies are introduced into treatment strategies for children 2.7.10.1 receptor protein-tyrosine kinase drug development using the split TEV recruitment assay and integrating the universal SH2(GRB2) adapter may represent a promising approach to build a technology platform to assess receptor tyrosine kinase activities in early drug discovery to finally improve compound selectivity 2.7.10.2 non-specific protein-tyrosine kinase drug development JAK2 is a target for drug development, specific inhibitors are of tremendous clinical relevance 2.7.10.2 non-specific protein-tyrosine kinase drug development non-receptor PTKs are targets for design by computational chemistry of therapeutic agents based on plant-derived inhibitors from ethnopharmaceutical knowledge, high-throughput screening, tyrosine kinase inhibitors can target the ATP or the substrate binding sites, respectively, strategies, detailed overview 2.7.10.2 non-specific protein-tyrosine kinase drug development PTKS are key targets for anticancer drug discovery 2.7.10.2 non-specific protein-tyrosine kinase drug development the enzyme is a target for development and evaluation of tyrosine kinase inhibitors 2.7.10.2 non-specific protein-tyrosine kinase drug development tyrosine kinase Src is a key enzyme in mammalian signal transduction and an important target for anticancer drug discovery 2.7.11.1 non-specific serine/threonine protein kinase drug development protein kinases are major targets for drug development and design in the pharmaceutical industry 2.7.11.1 non-specific serine/threonine protein kinase drug development CK2 is a target for drug development and design of selective inhibitors 2.7.11.1 non-specific serine/threonine protein kinase drug development the kinase activity of protein kinase Balpha has received considerable attention as a drug target, since protein kinase Balpha is constituently active in cancerous cells and requires strict regulation, inhibition of phosphatidylinositol 3,4,5-trisphosphate binding to the PH domain by small molecules has also become a priority target for anticancer treatment 2.7.11.1 non-specific serine/threonine protein kinase drug development the eukaryotic-like serine/threonine protein kinases are targets for the treatment of tuberculosis 2.7.11.2 [pyruvate dehydrogenase (acetyl-transferring)] kinase drug development development of specific inhibitors of PDK4 has become an especially important focus for the pharmaceutical management of diabetes and obesity 2.7.11.10 IkappaB kinase drug development because of its central role in the overall NF-kappaB regulation, IKK-2 is a viable target for drug discovery 2.7.11.11 cAMP-dependent protein kinase drug development recombinant PKA can be mutated to resemble Akt/PKB, which cannot be easily recombinantly expressed, mutant PKA can be used as surrogate enzyme for Akt/PKB in drug design 2.7.11.11 cAMP-dependent protein kinase drug development the enzyme represents an attractive target for the development of anti-malarial drugs 2.7.11.12 cGMP-dependent protein kinase drug development enzyme is a target for drug development 2.7.11.12 cGMP-dependent protein kinase drug development the enzyme is a target for antiparasitic drugs, e.g. pyrrole 4-[2-(4-fluorophenyl)-5-(1-methylpiperidine-4-yl)-1H pyrrol-3-yl] pyridine 2.7.11.12 cGMP-dependent protein kinase drug development the enzyme is a target for drug development 2.7.11.21 polo kinase drug development BI 2536 is well tolerated 2.7.11.21 polo kinase drug development promoter of PLK is an esophageal tumor-specific promoter and may serve as useful tool in the establishment of a transcriptional targeting strategy for esophageal cancer gene therapy 2.7.11.21 polo kinase drug development roles of Plk1 in cell cycle progression and in mitosis, role for Plk1 in the activation of the CDK1-Cyclin B complex. Plk1 is required not only to obtain, but also to maintain, chromosome bi-orientation on the mitotic spindle, use of BI 2536, a small-molecule inhibitor of Plk1, as an analytical tool and potential cancer therapeutic 2.7.11.21 polo kinase drug development because the polo-box domain is unique to the five-member family of polo-like kinases, and its inhibition is sufficient to inhibit the enzyme, the Plk1 PBD is an attractive target for the inhibition of Plk1 function 2.7.11.21 polo kinase drug development Plk1 is considered an attractive anti-cancer drug target due to its ability to promote tumorigenesis 2.7.11.22 cyclin-dependent kinase drug development CDK2 is a target for development of small molecule inhibitors binding to the ATP binding pocket, determinations of binding structures and design of an inhibitor scaffold, overview 2.7.11.22 cyclin-dependent kinase drug development CDKs are important targets for the design of drug with antimitotic and antineurodegenerative effects 2.7.11.24 mitogen-activated protein kinase drug development MAPKs are targets for drug development 2.7.11.24 mitogen-activated protein kinase drug development kinase inhibitors modulate proliferation of leukemia cells, the MEK/ERK inhibitor, PD098059, in combination with either SP600125, an inhibitor of N-terminal c-jun kinases, or LY294002, a PI3K inhibitor, could have clinical value 2.7.11.24 mitogen-activated protein kinase drug development Echinococcus multilocularis MPK2 is a promising target for the development of drugs against alveolar echinococcosis 2.7.11.24 mitogen-activated protein kinase drug development p38 MAPK inhibitors have significant therapeutic potential for the treatment of rheumatoid arthritis, inflammatory bowel disease, osteoporosis, and many other diseases where aberrant cytokine signaling is the driver of disease 2.7.11.26 tau-protein kinase drug development glycogen synthase kinase-3 activity and substrate phosphorylation, e.g. glycogen synthase, tau, CRMP2 and amyloid precursor protein, are reported to be abnormally high in both Type 2 diabetes and Alzheimer's disease. The enzyme GSK3 is a target for development of isozyme- and splice variant-selective inhibitors 2.7.11.26 tau-protein kinase drug development glycogen synthase kinase-3 activity and substrate phosphorylation, e.g. glycogen synthase, tau, CRMP2 and amyloid precursor protein, are reported to be abnormally high in both Type 2 diabetes and Alzheimer's disease. The enzyme GSK3 is a target for development of isozyme-selective inhibitors 2.7.11.26 tau-protein kinase drug development tau kinase are drug target candidates for small molecule inhibitors 2.7.11.31 [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase drug development pharmacological activators of AMPK can act as treatments for diabetes and the metabolic syndrome 2.7.11.31 [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase drug development activating AMPK may have therapeutic potential in treating dry macular degeneration 2.7.11.31 [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase drug development AMPK is a highly attractive target for the prevention and treatment of type 2 diabetes and other disorders of the metabolic syndrome, and to curb the prevalence and costs of type 2 diabetes 2.7.11.31 [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase drug development AMPK is regarded as one of the most promising targets for new drugs to treat the growing incidence of metabolic diseases such as obesity and type 2 diabetes and cardiovascular disease 2.7.11.31 [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase drug development AMPK represents an attractive therapeutic target for vascular disease treatment 2.7.11.31 [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase drug development targeting SIRT1-AMPK pathway may serve as a new target for the development of new anti HIV-1 agents 2.7.11.31 [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase drug development the AMPK inhibitor 6-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-3-pyridin-4-yl-pyrrazolo[1,5-a]-pyrimidine may serve as a useful molecule in both basic and clinical research on adipogenesis and as a potential lead compound for the treatment of obesity 2.7.11.31 [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase drug development the glucose-sensitive stimulatory impact of BLX-1002 on beta-cell function associated with AMPK activation may translate into substantial clinical benefits of the drug in the management of type 2 diabetes, by avoidance of hypoglycemia 2.7.11.31 [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase drug development triterpenoids are potential hypoglycemic components of the plant and the mechanism underlying their action involves AMPK 2.7.11.31 [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase drug development AMP-activated protein kinase (AMPK) is a potential target for drug design against metabolic syndrome, obesity and type 2 diabetes 2.7.11.31 [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase drug development AMPK alpha2beta2gamma3 is an attractive target for drug development for diabetes and metabolic syndrome 2.7.11.31 [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase drug development design and development of isoform-selective AMPK activators that are likely to be useful for the treatment of cardiovascular and metabolic diseases 2.7.12.1 dual-specificity kinase drug development the enzyme is a target in drug development for treatment of Alzheimer's disease 2.7.12.2 mitogen-activated protein kinase kinase drug development design and synthesis of a new series of MEK1 inhibitors, the 4-anilino-5-carboxamido-2-pyridones 2.7.12.2 mitogen-activated protein kinase kinase drug development because of their importance in cell proliferation and signaling, MAPK pathways are being targeted for drugs for oncology, inflammation and other conditions. MEK inhibitors may be beneficial for cancer therapy. MEK inhibition is likely to be of particular importance in specific tumors where the MEK pathway is highly and directly activated 2.8.2.30 [heparan sulfate]-glucosamine 3-sulfotransferase 3 drug development introduction of a single sulfate group into the heparin octasaccharide is sufficient for effective blocking of HSV-1 infection 3.1.1.1 carboxylesterase drug development development and application of hiCE-specific inhibitors designed to selectively modulate drug hydrolysis in vivo 3.1.1.1 carboxylesterase drug development the major human hepatic hydrolase, carboxylesterase 1 serves as a target of metabolic inhibition by a variety of medications 3.1.1.1 carboxylesterase drug development SexiCXE10 acts as a general odorant-degrading enzyme, showing the potential to be a target for developing behavioral antagonists and pesticides against Spodoptera exigua 3.1.1.2 arylesterase drug development resistance of strains to permethrin is associated with elevated levels of enzyme 3.1.1.4 phospholipase A2 drug development development of Lp-PLA2 inhibitors as therapy for atherosclerosis 3.1.1.4 phospholipase A2 drug development Lp-PLA2 is proposed as a promising target for drug discovery 3.1.1.4 phospholipase A2 drug development applicability of minocycline as a lead compound for the design of specific inhibitors of PLA2, which play a crucial role in inflammatory processes 3.1.1.4 phospholipase A2 drug development capacity of the cPLA2-alpha inhibitors to block or reduce simultaneously the production of the two major classes of lipid mediators, eicosanoids and platelet activating factor, potentially endows these molecules with a very potent anti-inflammatory activity. The cPLA2-alpha inhibitors AZ-1 and pyrrolidine-1 are effective at submicromolar concentrations when macrophages are stimulated by physiological agonists (Mycobacterium tuberculosis purified protein derivative and lipopolysaccharide) provides a rationale for the use of these inhibitors in the treatment of inflammatory lung diseases 3.1.1.4 phospholipase A2 drug development design of new analogues with enhanced binding energy in the GIIA sPLA2 active site by systematic modifications of the pharmacophore segments of the FPL67047XX inhibitor 3.1.1.4 phospholipase A2 drug development herbal compounds (acalyphin, chlorogenic acid, stigmasterol, curcumin and tectoridin) and marine compounds (gracilin A and aplysulphurin A) show favorable interactions with the amino acid residues at the active site of PLA2, thereby substantiating their proven efficacy as anti-inflammatory compounds and antidotes 3.1.1.4 phospholipase A2 drug development influence on regulation of sPLA2(IIA) activity can be useful in the development of new therapeutic approaches to the treatment of cardiovascular diseases 3.1.1.4 phospholipase A2 drug development inhibition of iPLA2 and lysophospholipid production may be of interest to reduce Ca2+ entry and subsequent degeneration of dystrophic muscle 3.1.1.4 phospholipase A2 drug development new pharmaceutical approaches against PLA2 activity can be designed to prevent either membrane adsorption or nonhydrolytic bilayer-disrupting activity, both of which are necessary for enzymatic activity, opening up a new set of specific functional targets for inhibitor design 3.1.1.4 phospholipase A2 drug development partial inhibition of PLA2-V by most fruit antioxidants may prove advantageous in vivo in that basal levels of phospholipid-derived mediators may be maintained for normal brain function. The sPLA2-V inhibition by anthocyanidins provides further evidence to rationalize antioxidative and antiinflammatory activities 3.1.1.4 phospholipase A2 drug development possibilities of enhanced rational drug design against GIVA PLA2 through the powerful combination of experimental and computational work (deuterium exchange mass spectrometry and molecular dynamics simulation) 3.1.1.4 phospholipase A2 drug development potential therapeutic role for cPLA2 alpha inhibitors in the treatment of human rheumatoid arthritis. Oral administration of pyrroxyphene achieves anti-arthritic activity through inhibition of cPLA2 alpha activity, which leads to a reduction in eicosanoid levels and suppression of matrix metalloproteinases and cyclooxygenase-2 mRNA expression 3.1.1.4 phospholipase A2 drug development sPLA2s and Lp-PLA2 inhibitors darapladib and varespladib emerge as promising therapeutical options for treating patients with coronary artery disease. Lp-PLA2 inhibition may favorably affect rupture-prone lesions 3.1.1.4 phospholipase A2 drug development targeted inhibition of PLA2- and autotaxin-mediated lysophosphatidic acid synthesis may be a potential strategy for the prevention of nerve injury-induced neuropathic pain 3.1.1.4 phospholipase A2 drug development the mechanisms by which IL-1beta-induces cPLA2 expression may be an important link in the pathogenesis of airway inflammatory diseases. Understanding these mechanisms underlying IL-1beta-induced cPLA2 expression in human tracheal smooth muscle cells is important to develop new therapeutic strategies 3.1.1.4 phospholipase A2 drug development with the classification of GVIIA PLA2 as a positive risk factor in coronary heart disease, it has become a very attractive drug target. Recent clinical trials with GVIIA PLA2 inhibitor have shown a decrease in the complex atherosclerotic lesions that lead to unstable lesions, as well as other cardiovascular disease markers 3.1.1.7 acetylcholinesterase drug development AChE, when conjugated with organophosphorous compounds, is employed as a template for socalled click-chemistry, freeze-frame synthesis of nucleophilic reactivating agents that could potentially prove useful in AChE reactivation at the target site as well as in catalytic scavenging of organophosphates in plasma, overview 3.1.1.7 acetylcholinesterase drug development the enzyme is a target for rational drug design 3.1.1.7 acetylcholinesterase drug development AChE is a target for development of improved inhibitots in therapy of Alzheimer's disease 3.1.1.7 acetylcholinesterase drug development AChE is an important drug target and its inhibitors prove useful in the symptomatic treatment of Alzheimer's disease 3.1.1.7 acetylcholinesterase drug development development of inhibitors with therapeutic potential to dually target inflammation by releasing an non-steroidal anti-inflammatory drug, e.g. ibuprofen, naproxen, indomethacin, or diclofenac, in vivo and activating the cholinergic anti-inflammatory pathway via cholinergic up-regulation, overview 3.1.1.7 acetylcholinesterase drug development the enzyme is a target for development of drugs for use in therapy of Alzheimer's diesease 3.1.1.7 acetylcholinesterase drug development acetylcholinesterase, butyrylcholinesterase and beta-amyloid are the predominant biological targets in the search for anti-Alzheimer's agents 3.1.1.7 acetylcholinesterase drug development the simplified DNP derivatives may represent structural templates for the design of lead compounds for a more effective therapeutic strategy against Alzheimer's disease by foreseeing a dual AChE and BACE-1 inhibitory activity 3.1.1.8 cholinesterase drug development acetylcholinesterase, butyrylcholinesterase and beta-amyloid are the predominant biological targets in the search for anti-Alzheimer's agents 3.1.1.8 cholinesterase drug development enzyme BChE is a promising drug target in advanced Alzheimer's disease. (+/-)-N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2-(dimethylamino)ethyl)-2-naphthamide is thus a promising advanced lead compound for the development of drugs for alleviating symptoms of cholinergic hypofunction in patients with advanced Alzheimer's disease 3.1.1.23 acylglycerol lipase drug development the enzyme is a target for design of potent and selective inhibitors 3.1.1.23 acylglycerol lipase drug development potent MGL inhibitors with selectivity over FAAH may be realized by exploiting structural difference as well as the binding sub-pocket, increased volume around the catalytic site, and potential hydrogen-bonding opportunities 3.1.1.23 acylglycerol lipase drug development selective inhibitors of MGL may be valuable novel agents for the treatment of inflammatory pain. (2S,9Z)-octadec-9-ene-1,2-diamine is a selective inhibitor of MGL activity with in vivo analgesic and anti-inflammatory properties 3.1.1.23 acylglycerol lipase drug development structure of MAGL paves the way for future medicinal chemistry works aimed at the design of new drugs exploiting 2-arachidonoylglycerol transmission. MAGL is a hot therapeutic target, because the design of selective and potent inhibitors can provide unique tools to interfere with 2-arachidonoylglycerol degradation and to finely modulate the endocannabinoid signal 3.1.1.23 acylglycerol lipase drug development Differences in the binding pocket of mtbMGL compared to human MGL open the possibility for specific inhibition of MGL from the pathogen Mycobacterium tuberculosis and use in the human pathogen treatment 3.1.1.29 aminoacyl-tRNA hydrolase drug development Pth is a potential drug target to control eubacterial infections 3.1.1.31 6-phosphogluconolactonase drug development the enzyme is a target for anti-parasite drug development 3.1.1.43 alpha-amino-acid esterase drug development valacyclovirase is suggested as a prodrug activating enzyme 3.1.1.43 alpha-amino-acid esterase drug development in hVACVase-catalyzed reactions, the leaving group of the substrate corresponds to the drug moiety of the prodrug, making the leaving group effect essential for the rational design of prodrugs targeting hVACVase activation 3.1.1.53 sialate O-acetylesterase drug development broad-spectrum antivirals that target orthomyxo- and coronavirus sialate-O-acetylesterases 3.1.1.53 sialate O-acetylesterase drug development drug design, two essential pharmacophoric groups of ligand: 9-O-acetyl group and C-1 carboxylate group, anti-virus infection 3.1.1.58 N-acetylgalactosaminoglycan deacetylase drug development the enzyme is a good target for therapeutic intervention in biofilm related infections 3.1.1.79 hormone-sensitive lipase drug development the requirement of dimerization for the function and stability of HSL-family enzymes focuses attention on the dimeric interface as a potential target for structure-aided drug design 3.1.1.81 quorum-quenching N-acyl-homoserine lactonase drug development Ahl-1 lactonase is considered a promising therapeutic agent to inhibit Pseudomonas aeruginosa pathogenicity with no fear of emergence of resistance 3.1.1.81 quorum-quenching N-acyl-homoserine lactonase drug development MomL significantly attenuates the virulence of Pseudomonas aeruginosa in a Caenorhabditis elegans infection model, which suggests that MomL has the potential to be used as a therapeutic agent 3.1.1.81 quorum-quenching N-acyl-homoserine lactonase drug development potential use of Aii20J in the control of the expression of virulence and adaptation genes in important human pathogens 3.1.1.81 quorum-quenching N-acyl-homoserine lactonase drug development the AHL-lactonase from Enterobacter aerogenes VT66 can be used as antibiofilm therapeutics in Pseudomonas aeruginosa associated biomedical applications 3.1.1.81 quorum-quenching N-acyl-homoserine lactonase drug development the enzyme significantly inhibits the biofilm formation and attenuates extracellular proteolytic activity and pyocyanin production of Pseudomonas aeruginosa PAO1, which indicates the potential application of AiiK as a biocontrol agent or an anti-pathogenic drug 3.1.1.81 quorum-quenching N-acyl-homoserine lactonase drug development use of purified AiiATSAWB, as hypertonic suspension for inhalation to substitute the action of inactivated host's paraoxonase in treating Pseudomonas aeruginosa infection in cystic fibrosis patients 3.1.1.98 [Wnt protein] O-palmitoleoyl-L-serine hydrolase drug development NOTUM inhibitors have potential for treating degenerative diseases 3.1.1.116 sn-1-specific diacylglycerol lipase drug development inhibitors of diacylglycerol lipases and alpha,beta-hydrolase domain containing protein 6 (ABHD6) are potential leads for the development of therapeutic agents for metabolic and neurodegenerative disorders 3.1.2.6 hydroxyacylglutathione hydrolase drug development cancer therapy, inhibitors of the glyoxalase system would be expected to suppress the growth of cancer cells and could find clinical use as anticancer drug 3.1.3.4 phosphatidate phosphatase drug development the PAP1 colorimetric assay with pure enzyme and a water-soluble phosphatidate substrate is applicability to a 96-well format, which may facilitate a large-scale screen of PAP1 inhibitors (or activators) 3.1.3.11 fructose-bisphosphatase drug development the enzyme is a target for drug development in treatment of type 2 diabetes mellitus 3.1.3.11 fructose-bisphosphatase drug development the structure of the effector site of LmFBPase shows different structural features compared with human FBPases, thereby offering a potential and species-specific drug target 3.1.3.12 trehalose-phosphatase drug development Bm-TPP bodes well as a rational drug target against lymphatic filariasis 3.1.3.12 trehalose-phosphatase drug development enzyme MtbTPP (OtsB2) is considered a promising potential target for discovery of antimicrobial drugs 3.1.3.15 histidinol-phosphatase drug development the absence of a histidine biosynthesis pathway in humans, coupled with histidine essentiality for survival of the important human pathogen Mycobacterium tuberculosis (Mtb), underscores the importance of the bacterial enzymes of this pathway as major antituberculosis drug targets 3.1.3.16 protein-serine/threonine phosphatase drug development calcineurin is the principal target of the immunosuppressive drugs, cyclosporin A and FK506/Tacrolimus, the binding of which physically prevents the recruitment of macromolecular substrates to the active site 3.1.3.25 inositol-phosphate phosphatase drug development the enzyme is a target for development of lithium-mimetic agents for the treatment of bipolar disorder, high-throughput cell-based screening using scintillation proximity assay for the discovery of enzyme inhibitors, overview 3.1.3.34 deoxynucleotide 3'-phosphatase drug development introduction of substituents in the 3'-position may result in nucleoside analogues with increased resistance to dephosphorylation, design of drugs that are less prone to inactivation by the deoxyribonucleotidases 3.1.3.48 protein-tyrosine-phosphatase drug development the enzyme is a target for inhibitor design 3.1.3.48 protein-tyrosine-phosphatase drug development inhibition of MptpA and MptpB represents a promising strategy for the development of selective antibiotics against this severe pathogen 3.1.3.48 protein-tyrosine-phosphatase drug development MptpB is a promising target for anti-tuberculosis drug development 3.1.3.48 protein-tyrosine-phosphatase drug development MptpB is a promising target for development of anti-tuberculosis drugs 3.1.3.48 protein-tyrosine-phosphatase drug development PTP1B is a target for drug development in treatment of type II diabetes and obesity 3.1.3.67 phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase drug development This study is a direct evidence for a model in which PTEN switches between open and closed states and phosphorylation favors the closed conformation, thereby regulating localization and function. Small molecules targeting these interactions can potentially serve as therapeutic agents in antagonizing Ras or phosphoinositide 3-kinase-driven tumors. 3.1.3.74 pyridoxal phosphatase drug development important in vitamin B6 metabolism 3.1.3.74 pyridoxal phosphatase drug development possibility of development of the pyridoxine production process by a metabolic engineering approach. In the future, overexpression of the pdxP gene in combination with another pyridoxine gene will be necessary to develop even more efficient processes for production of vitamin B6 3.1.3.74 pyridoxal phosphatase drug development transduction of the PEP-1-PLPP fusion protein into cells would be useful as therapeutic agent for various disorders related to this enzyme and vitamin B6 3.1.4.1 phosphodiesterase I drug development the enzyme is a possible target for drug design in treatment of calcium pyrophosphate dehydrate deposition disease. PC-1 interferes with insulin receptor signaling, a link between mutations in PC-1 and insulin resistance. PC-1 inhibitors may therefore also have use in treating diabetic patients 3.1.4.1 phosphodiesterase I drug development the enzyme is a a therapeutic target. It is of growing interesting in cancer treatment for its role in the repair of a variety of DNA adducts that are induced by chemotherapeutics 3.1.4.2 glycerophosphocholine phosphodiesterase drug development possible vaccination, Protein D is immunogenic in human. Vaccine containing polysaccharides from 7 serotypes (each conjugated to CRM197, a nontoxic mutant of diphtheria toxin that is an immunogenically inactive carrier) shows high efficacy in young children. Experiments with rats: vaccination with Protein D induces high levels of serum IgG and IgA antibodies and significant bactericidal activity against homologous and heterologous strains (rat middle ear clearance model, rat pulmonary clearance model). Pronounced activity of Protein D antibodies is shown in the chinchilla acute otitis media model 3.1.4.3 phospholipase C drug development elucidation of the mechanisms responsible for aberrant phosphatidylcholine metabolism in cancer cells may allow identification of novel biomarkers of tumor progression and design of new targeted anticancer therapies 3.1.4.11 phosphoinositide phospholipase C drug development PLCgamma1 inhibitors may have potential therapeutic applications for the clinical treatment of tumor metastasis 3.1.4.12 sphingomyelin phosphodiesterase drug development TbnSMase is therefore genetically validated as a drug target against African trypanosomes, and suggests that interfering with the endocytic transport of variant surface glycoprotein is a highly desirable strategy for drug development against African trypanosomasis 3.1.4.12 sphingomyelin phosphodiesterase drug development acid sphingomyelinase activity and sphingomyelin presence are necessary for efficient infection of cells by ebolavirus,the enzym eis a target for drug development 3.1.4.39 alkylglycerophosphoethanolamine phosphodiesterase drug development ATX is one of the target molecules for cancer therapy, therefore the immuno-neutralization by an antibody which is able to recognize the catalytic site, or the low molecular weight chemical inhibitors based on structural biology should be a useful tool for prevention or treatment of tumor progression and metastasis 3.1.4.39 alkylglycerophosphoethanolamine phosphodiesterase drug development to inhibit lysophosphatidic acid production in the blood. Inhibition of autotaxin/lysoPLD activity by small molecules could be an effective new therapeutic approach for cancer and possibly cardiovascular disease 3.1.4.39 alkylglycerophosphoethanolamine phosphodiesterase drug development ATX is a target for cancer treatment 3.1.4.39 alkylglycerophosphoethanolamine phosphodiesterase drug development the enzyme is a good target for small molecule inhibitors 3.1.4.46 glycerophosphodiester phosphodiesterase drug development the enzyme might be a promising target for anti-malaria drug development 3.1.6.13 iduronate-2-sulfatase drug development HIRMAb-IDS fusion protein is a bifunctional IgG-sulfatase fusion protein, specifically engineered for targeted drug delivery across the human blood-brain barrier 3.1.8.1 aryldialkylphosphatase drug development PON1 variants with catalytic efficacy that will qualify them as potential drug candidate for prophylactic treatment of nerve agent intoxication 3.1.11.1 exodeoxyribonuclease I drug development inhibition of a newly synthesized fullerene-oligonucleotide conjugate against PCR-amplification of targeted DNA and the enzymatic activity of an engineered DNA enzyme, Exo I 3.1.13.2 exoribonuclease H drug development HIV-1 RNase H is an attractive molecular target for developing anti-HIV agents for potential chemotherapeutic applications 3.1.13.2 exoribonuclease H drug development HIV-2 RNase H is an attractive molecular target for developing anti-HIV agents for potential chemotherapeutic applications 3.1.13.2 exoribonuclease H drug development RNase H is an anti-viral target 3.1.13.2 exoribonuclease H drug development the enzyme is a target for anti-HIV drug development 3.1.13.2 exoribonuclease H drug development development of anti-HIV agents which can be used alone or in the combination with other HIV inhibitors in AIDS chemotherapy 3.1.13.2 exoribonuclease H drug development reverse transcriptase is a primary target for antiretroviral therapy of HIV-1 infected patients. While the vast majority of anti-virals are specific for the polymerase domain, the RNaseH activity of reverse transcriptase represents an excellent target for antiretroviral drugs as well 3.1.13.2 exoribonuclease H drug development RNase H activity associated with human immunodeficiency virus type 1 is an attractive target for an antiretroviral drug development 3.1.13.2 exoribonuclease H drug development viruses deficient in RNase H activity are non-infectious making RNase H an interesting target for anti-HIV inhibitors 3.1.13.2 exoribonuclease H drug development an active recombinant His6-tagged HBV RNaseH is suitable for low-throughput drug screening and can be used to discover enzyme inhibitors, many of which work against viral replication in cells 3.1.13.2 exoribonuclease H drug development the HBV ribonuclease H (RNaseH) as an antiviral drug target 3.1.21.7 deoxyribonuclease V drug development investigated as a chemopreventive agent of nonmelanoma skin cancer 3.1.26.4 ribonuclease H drug development an active recombinant His6-tagged HBV RNaseH is suitable for low-throughput drug screening and can be used to discover enzyme inhibitors, many of which work against viral replication in cells 3.1.26.4 ribonuclease H drug development RnhC in pathogenic mycobacteria is a possible candidate drug discovery target for tuberculosis and leprosy 3.1.26.4 ribonuclease H drug development the HBV ribonuclease H (RNaseH) as an antiviral drug target 3.1.26.13 retroviral ribonuclease H drug development the enzyme is a drug target 3.1.26.13 retroviral ribonuclease H drug development RNase H activity is an attractive target for a new class of antiviral drugs 3.1.26.13 retroviral ribonuclease H drug development the enzyme is a target for the development of effective dual HIV-1 IN and RNase H inhibitors 3.1.26.13 retroviral ribonuclease H drug development the HIV RT-associated RNase H is avaluable drug target 3.1.31.1 micrococcal nuclease drug development attractive potential target for the development of anti-malarial drugs 3.1.31.1 micrococcal nuclease drug development generation of Vibrio anguillarum ghost by coexpression of PhiX 174 Lysis E gene and SNA gene, potential vaccine for fishes against vibriosis 3.1.99.B1 flap endonuclease-1 drug development inhibitors of the enzyme carry a potential as enhancers of DNA-interactive anticancer drugs 3.2.1.6 endo-1,3(4)-beta-glucanase drug development the various truncated proteins of LamA also show inhibition on the mycelium growth of Rhizopus solani, a pathogen infecting a broad range of many crops, suggesting the application potential of LamA as an antifungal agent in many aspects 3.2.1.11 dextranase drug development fractionated dextrans possess commercial interest in cosmetics, drug formulations, vaccines, cryoprotectants 3.2.1.31 beta-glucuronidase drug development stable expression of GusA in Gardia lamblia strain WB C6 for establishing a system to test enzyme susceptibility to the anti-giardial drugs nitazoxanide and metronidazole, overview 3.2.1.40 alpha-L-rhamnosidase drug development the characteristics (good thermostability, wide range of pH-stability with the optimum pH of 5.0 and temperature of 60°C, not greatly affected by representative metal ions, excellent tolerance abilities against glucose and ethanol) of the enzyme suggest that it should be considered a potential new biocatalyst for food and drug industrial applications 3.2.1.46 galactosylceramidase drug development enhancers of beta-galactocerebrosidase are identified as potential small molecules therapies for Krabbe's disease 3.2.1.52 beta-N-acetylhexosaminidase drug development the enzyme is a target for GlcNAc-inspired iminocyclitiols drug development 3.2.1.55 non-reducing end alpha-L-arabinofuranosidase drug development enzymatic purification of saccharides 3.2.1.76 L-iduronidase drug development mutant AGT-181 might be useful as a therapeutic approach to treatment of the brain in Hurler’s syndrome 3.2.1.78 mannan endo-1,4-beta-mannosidase drug development the enzyme is a target for the development of inhibitor molecules to be used in pest control strategies to reduce the serious damage caused by the coffee berry borer during coffee cultivation 3.2.1.113 mannosyl-oligosaccharide 1,2-alpha-mannosidase drug development development of anti-cancer therapies 3.2.1.114 mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase drug development development of specific inhibitors of GMII that can lead to novel anti-metastatic or anti-inflammatory compounds 3.2.1.114 mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase drug development the enzyme Golgi alpha-mannosidase II is a promising target for intervention in the glycosylation process 3.2.1.123 endoglycosylceramidase drug development rational redesign of EGC toward the synthesis of novel ganglioside-derived therapeutics 3.2.1.143 poly(ADP-ribose) glycohydrolase drug development the enzyme is a target for drug design 3.2.1.143 poly(ADP-ribose) glycohydrolase drug development the enzyme is a target for development of specific inhibitors 3.2.1.143 poly(ADP-ribose) glycohydrolase drug development inhibitors of the enzyme are potent anticancer drug candidates 3.2.1.143 poly(ADP-ribose) glycohydrolase drug development the protozoan enzyme represents a good model for human PARG and is therefore likely to prove useful in guiding structure-based discovery of new classes of PARG inhibitors 3.2.1.143 poly(ADP-ribose) glycohydrolase drug development DNA damage repair enzymes, including the enzyme poly(ADP-ribose) glycohydrolase (PARG), are promising targets in the development of therapeutic agents for a wide range of cancers and potentially other diseases 3.2.1.143 poly(ADP-ribose) glycohydrolase drug development single treatment therapy with PARG inhibitors can be used for treatment of certain homologous recombination-deficient tumours 3.2.1.166 heparanase drug development heparanase is an important target for anti-cancer and anti-inflammatory drug discovery 3.2.1.166 heparanase drug development the enzyme is a very attractive target in drug discovery 3.2.1.166 heparanase drug development heparanase inhibitors used in tandem with chemotherapeutic drugs overcome initial chemoresistance, providing a strong rationale for applying anti-heparanase therapy in combination with conventional anti-cancer drugs. Heparin-like compounds that inhibit heparanase activity are being evaluated in clinical trials for various types of cancer. Heparanase expressed by tumor cells, innate immune cells, activated endothelial cells as well as other cells of the tumor microenvironment is a prime target for therapy 3.2.1.166 heparanase drug development overexpression of hepaxadranase in cancers is well known and is associated with angiogenesis, inflammation and increased metastatic potential, making this enzyme a promising drug target 3.2.1.166 heparanase drug development the emerging role of heparanase in tumor initiation, growth, metastasis, and chemoresistance is well recognized and is encouraging the development of heparanase inhibitors as anticancer drugs for humans 3.2.1.166 heparanase drug development the natural heparan sulfate-heparanase interactions are used as a template for the design of heparan sulfate-mimicking glycopolymers 3.2.1.166 heparanase drug development the upregulation of heparanase expression increases tumor size, angiogenesis, and metastasis, represents a validated target in the anti-cancer field. 2-(4-(4-(bromo-methoxybenzamido)benzylamino)phenyl) benzazole derivatives act as anti-heparanase agents, proposing this scaffold for development of broadly effective heparanase inhibitors. Symmetrical 2-aminophenyl benzazolyl-5-acetate derivatives, proving that symmetrical compounds, are more effective than asymmetrical analogues 3.2.2.1 purine nucleosidase drug development enzyme inhibitors N-arylmethyl-substituted iminoribitol derivatives as potential chemotherapeutic agents against trypanosomiasis, validation in an in vivo model of African trypanosomiasis 3.2.2.9 adenosylhomocysteine nucleosidase drug development potential of MTAN as target for bacterial anti-infective drug design 3.2.2.16 methylthioadenosine nucleosidase drug development the enzyme is a potential target for specific antibiotics 3.2.2.27 uracil-DNA glycosylase drug development inhibitor design and development, inhibition of UNG could be a rational strategy for the treatment of infections with poxviruses 3.2.2.27 uracil-DNA glycosylase drug development the UDG from Mycobacterium smegmatis might be a useful target for inhibitor design 3.3.2.6 leukotriene-A4 hydrolase drug development development of LTA4H inhibitors in cancer prevention and therapy 3.3.2.6 leukotriene-A4 hydrolase drug development Drug repurposing of histone deacetylase inhibitors that alleviate neutrophilic inflammation in acute lung injury and idiopathic pulmonary fibrosis via inhibiting leukotriene A4 hydrolase and blocking LTB4 biosynthesis 3.3.2.6 leukotriene-A4 hydrolase drug development drug repurposing of histone deacetylase inhibitors that alleviate neutrophilic inflammation in acute lung injury and idiopathic pulmonary fibrosis via inhibiting leukotriene A4 hydrolase and blocking LTB4 biosynthesis. Inhibiting LTB4 biosynthesis and subsequently neutrophilic inflammation may provide a potential strategy for the treatment of acute lung injury (ALI) and idiopathic pulmonary fibrosis (IPF) 3.3.2.6 leukotriene-A4 hydrolase drug development possible therapeutic potential of targeting LTB4/BLT signaling in asthma, but production of LTB4 may not be responsible for airway neutrophils in severe asthma 3.3.2.6 leukotriene-A4 hydrolase drug development the bifunctional enzyme is a target for development of selective inhibitors 3.3.2.9 microsomal epoxide hydrolase drug development the enzyme is a target for inhibitor design 3.3.2.9 microsomal epoxide hydrolase drug development the enzyme is an important therapeutic target for chronic diseases such as hypertension, diabetes and inflammation 3.3.2.10 soluble epoxide hydrolase drug development sEH is a cross-functional target with the potential for therapeutic utility in the areas of hypertension, inflammation, and organ protection 3.3.2.10 soluble epoxide hydrolase drug development sEH is a target for drug design, since inhibition of sEH leads to an increase in circulating levels of epoxyeicosatrienoic acids, resulting in the potentiation of their in vivo pharmacological properties 3.3.2.10 soluble epoxide hydrolase drug development the enzyme is a promising target for drug development 3.3.2.10 soluble epoxide hydrolase drug development soluble epoxide hydrolase (sEH) is a potential target for the treatment of inflammation and hypertension 3.3.2.10 soluble epoxide hydrolase drug development the enzyme is an important therapeutic target for chronic diseases such as hypertension, diabetes and inflammation 3.3.2.11 cholesterol-5,6-oxide hydrolase drug development the enzyme is a target for inhibition of the 6-oxo-cholestan-3beta,5alpha-diol (OCDO) biosynthesis in cancer therapy 3.4.11.1 leucyl aminopeptidase drug development the enzyme represents a target for which antimalarials can be designed since metalloaminopeptidase inhibitors prevent the growth of the parasites in vitro and in vivo 3.4.11.1 leucyl aminopeptidase drug development LAP-A as a potential drug target in Trypanosoma brucei 3.4.11.2 membrane alanyl aminopeptidase drug development aminopeptidase N is a target for development of specific inhibitors 3.4.11.2 membrane alanyl aminopeptidase drug development the membrane alanyl aminopeptidase is a target to modulate keratinocyte growth and differentiation 3.4.11.6 aminopeptidase B drug development Drug repurposing of histone deacetylase inhibitors that alleviate neutrophilic inflammation in acute lung injury and idiopathic pulmonary fibrosis via inhibiting leukotriene A4 hydrolase and blocking LTB4 biosynthesis 3.4.11.7 glutamyl aminopeptidase drug development the enzyme is a target for design of specific inhibitors 3.4.11.7 glutamyl aminopeptidase drug development development of potent and selective APA inhibitors crossing the blood-brain barrier after oral administration for use as centrally-acting antihypertensive agents 3.4.11.9 Xaa-Pro aminopeptidase drug development the enzyme PfAPP might be a potential target for an antimalarial therapeutic strategy 3.4.11.18 methionyl aminopeptidase drug development MetAP is a promising target for developing broad spectrum antibacterial agents 3.4.11.18 methionyl aminopeptidase drug development the isoyzmes are targets for the development of antimalarial drugs, and ienzyme inhibitors may be useful as anticancer compounds 3.4.11.18 methionyl aminopeptidase drug development the MetAP isozymes are potential targets to develop antitubercular therapeutics 3.4.11.21 aspartyl aminopeptidase drug development enzyme TgAAP deletion results in inhibition, but not abolition, of invasion and growth of Toxoplasma gondii in cell culture, thus indicating that the enzyme may be a promising adjunct target for anti-toxoplasma drug development 3.4.11.21 aspartyl aminopeptidase drug development the M18 aspartyl aminopeptidase is a valid target to develop antimalarial drugs 3.4.11.21 aspartyl aminopeptidase drug development the M18 aspartyl aminopeptidase is a valid target to develop antimalarial drugs against the drug resistant strains of malaria parasite 3.4.13.9 Xaa-Pro dipeptidase drug development the enzyme is a target in breast cancer therapy 3.4.13.9 Xaa-Pro dipeptidase drug development the enzyme is used as target enzyme for specific melanoma prodrug activation 3.4.13.9 Xaa-Pro dipeptidase drug development prolidase is a potential biomarker for melanoma, and the enzyme is a target for drug development in cancer therapy 3.4.14.5 dipeptidyl-peptidase IV drug development a three-dimensional pharmacophore model is a useful tool for designing novel DPP-IV inhibitors 3.4.15.1 peptidyl-dipeptidase A drug development ACE is the molecular targets of inhibitory drugs that favorably influence diabetic complications 3.4.15.1 peptidyl-dipeptidase A drug development important drug target because of its role in the regulation of blood pressure via the renin-angiotensin-aldosterone system 3.4.15.1 peptidyl-dipeptidase A drug development marine-derived ACE inhibitors as therapeutic drug candidates to treat hypertension 3.4.17.1 carboxypeptidase A drug development the enzyme is a target for drug development for biotechnological and biomedical applications 3.4.17.1 carboxypeptidase A drug development the enzyme serves as model enzyme for design of specific inhibiors for zinc proteases 3.4.17.1 carboxypeptidase A drug development potential target for drug development 3.4.17.2 carboxypeptidase B drug development the enzyme is a target for design of active site inhibitors based on the structure of tick carboxypeptidase inhibitor, a potential antithrombolytic drug 3.4.17.10 carboxypeptidase E drug development carboxypeptidase E plays a role in the regulation of dopamine transporter trafficking and dopamine transporter-mediated dopamine uptake, which may provide a novel target in the treatment of dopamine-governed diseases such as drug addiction and obesity 3.4.17.11 glutamate carboxypeptidase drug development enzyme is used in enzyme prodrug therapy to treat human breast cancer, the enzyme catalyzes the activation of the di- and trifluorinated prodrugs 3.4.17.19 Carboxypeptidase Taq drug development potential target for drug development 3.4.17.21 Glutamate carboxypeptidase II drug development PSMA is a target for drug design 3.4.17.23 angiotensin-converting enzyme 2 drug development a super-potent tetramerized ACE2 protein displays enhanced neutralization of SARS-CoV-2 virus infection 3.4.19.1 acylaminoacyl-peptidase drug development enzyme APH is believed to be an important target for drug design 3.4.19.12 ubiquitinyl hydrolase 1 drug development three-step docking (DOCK, rough GOLD, and fine GOLD) and in vitro enzyme assay methods to identify UCH-L3 inhibitors. UCH-L3 inhibitors may be useful for future apoptosis-inducing anti-cancer drug development 3.4.19.12 ubiquitinyl hydrolase 1 drug development UCH54, homologous to human UCH37, may represent a target for pharmacological intervention 3.4.19.12 ubiquitinyl hydrolase 1 drug development the enzyme may contribute to the pathogenesis of idiopathic pulmonary fibrosis and may be a potential therapeutic target 3.4.21.1 chymotrypsin drug development design of a new class of boron peptides as inhibitors of the chymotrypsin-like activity of the 20S proteasome based around the structure of Belactosin C, proteasome inhibitors with therapeutic utility 3.4.21.1 chymotrypsin drug development enediyne-amino acid conjugates as potent inhibitors of alpha-chymotrypsin 3.4.21.1 chymotrypsin drug development G-quadruplex-scaffold-based receptors are effective inhibitors of ChT by protein-surface recognition. This may provide a general strategy to generate synthetic combinatorial libraries of receptors to target different classes of proteins 3.4.21.1 chymotrypsin drug development winged bean chymotrypsin-trypsin inhibitor is a dual inhibitor of both chymotrypsin and trypsin and a promising candidate to study for its insecticidal properties against Helicoverpa armigera and other insect pests 3.4.21.6 coagulation factor Xa drug development factor Xa is a target for development of anticoagulant therapeutics, drug development and clinical trials. overview 3.4.21.6 coagulation factor Xa drug development oral factor Xa inhibitors are a promising alternative to current anticoagulants 3.4.21.6 coagulation factor Xa drug development structure-based drug design of small molecule factor Xa inhibitors. fXa inhibi­tors, the so-called xabans, are attractive options that can overcome limitations, e.g. bleeding, of the current oral antithrombotic therapy, he rational design of small-molecule direct fXa inhibitors, overview 3.4.21.6 coagulation factor Xa drug development the enzyme is a target for drug development in prevention and treatment of thromboembolic disorders, overview 3.4.21.20 cathepsin G drug development the enzyme is a therapeutic target 3.4.21.21 coagulation factor VIIa drug development anti-thrombosis therapy 3.4.21.21 coagulation factor VIIa drug development treatment of thromboembolic disease 3.4.21.26 prolyl oligopeptidase drug development the discovery of enzyme inhibitors can revert memory loss caused by amnesic compounds in humans, developing a enzyme inhibitor from carbohydrate based materials 3.4.21.26 prolyl oligopeptidase drug development the enzyme is a pharmacological target for neurological diseases due to its high brain concentration and ability to cleave neuropeptides in vitro 3.4.21.26 prolyl oligopeptidase drug development the enzyme is a potential target for therapy of Chagas' disease 3.4.21.27 coagulation factor XIa drug development activated factor XI inhibition as a viable method to increase the ratio of benefit to risk in an antithrombotic drug 3.4.21.35 tissue kallikrein drug development pre-treatment with tissue kallikrein inhibitors and/or anti-angiogenic therapies may prove to benefit future cervical cancer patients 3.4.21.35 tissue kallikrein drug development recombinant adeno-associated virus-mediated tissue kallikrein gene delivery has multiple therapeutic possibilities for treating hypertension, not only by decreasing blood pressure, but also by directly inhibiting end-organ damage 3.4.21.35 tissue kallikrein drug development tissue kallikrein represents a promising therapeutic strategy for ischemic stroke 3.4.21.37 leukocyte elastase drug development neutrophil elastase may play be a target for the development of treatments for laminitis 3.4.21.37 leukocyte elastase drug development suppression of the enzyme reduces the risk of preterm delivery and improved neonatal outcomes and is therefore a target for inhibitor development 3.4.21.38 coagulation factor XIIa drug development a contact phase inhibitor of FXIIa is an effective and safe antithrombotic agent in vivo 3.4.21.42 complement subcomponent C1s drug development further probing for cooperativity may be of great value in the development of a peptide inhibitor for the C1s protease in the treatment of inflammatory disease 3.4.21.46 complement factor D drug development the enzyme's exosite is a target for design of specific inhibitors for inhibition of the pathway complement activation in advanced dry age-related macular degeneration 3.4.21.59 Tryptase drug development beta-tryptases are the major focus of drug development for therapeutic inhibition 3.4.21.61 Kexin drug development anti-PCSK9 antibodies may be effective therapeutics for treating hypercholesterolemia 3.4.21.61 Kexin drug development PCSK9 is a highly promising therapeutic target to lower low density lipoprotein-cholesterol and therefore prevent or reduce atherosclerosis 3.4.21.61 Kexin drug development the enzyme is a target for to drug development for inhibiting the PCSK9 processing pathway and ultimately disrupt the interaction with the LDL receptor, strategy for intracellular enzyme inhibition 3.4.21.61 Kexin drug development PCSK6 may become a reasonable target for the development of drugs able to control high blood pressure by directly modulating pro-ANP cleavage 3.4.21.68 t-Plasminogen activator drug development antifibrinolytic agents may be useful for protecting neurons when tPA-mediated damage is anticipated 3.4.21.68 t-Plasminogen activator drug development both TPA-antibiotic locks and heparin-antibiotic locks used in conjunction with systemic antibiotics can effectively clear catheter-related bacteraemia in children without significant late recurrence at 6 weeks. The mean infection-free survival of the catheters following TPA-antibiotic locks treatment is shorter than that following heparin–antibiotic locks treatment, but is not statistically significant 3.4.21.68 t-Plasminogen activator drug development neutrophils are good candidates to be the main source of metalloproteinase-9 following t-PA stroke treatment and in consequence, are partially responsible for thrombolysis-related brain bleedings. Combined therapy of t-PA with a metalloproteinase-9 or a neutrophil degranulation inhibitor may improve safety and efficacy of thrombolytic therapy in the acute phase of stroke 3.4.21.69 Protein C (activated) drug development at therapeutically relevant concentrations, activated protein C suppresses the release of interleukin-6 from stimulated human neutrophils and inhibited chemotaxis, without affecting the respiratory burst, apoptosis, and expression of other key cytokines. These effects are likely to be cell-type specific but may have implications for treatment of patients with activated protein C 3.4.21.72 IgA-specific serine endopeptidase drug development a fusion protein of the beta domain and a single-chain antibody to transmissible gastroenteritis coronavirus has been expressed on the surface of Escherichia coli. The single-chain antibody is then able to target and block the virus from infecting epithelial cells 3.4.21.73 u-Plasminogen activator drug development the enzyme is an attractive target for the development of small molecule active site inhibitors 3.4.21.73 u-Plasminogen activator drug development uPA is a potential therapeutic target in a variety of pathological conditions, including cancer 3.4.21.73 u-Plasminogen activator drug development complex formation of uPA and uPAR is a target for development of therapeutics 3.4.21.74 venombin A drug development VaaSPH-1 represents a very promising template to design low molecular mass FVIIIa-directed anticoagulant substances, based on structural features of the interaction surface between VaaSPH-1 and FVIIIa. Construction of a three-dimensional model of VaaSPH-1 bound to FVIIIa. The model exposes the 157-loop and the preceding alpha-helix as the most appropriate structural elements of VaaSPH-1 to be considered as a guideline to synthesize small FVIIIa-binding molecules, potential different generation of anticoagulants 3.4.21.75 Furin drug development extensive clinical use, high bioavailability and relatively low toxicity of dicoumarols suggests that the dicoumarol structure will be a good starting point for development of drug-like inhibitors of furin and other proprotein convertases that can act both intracellularly and at the cell surface 3.4.21.75 Furin drug development good prospect of using quantitative structure-activity relationship models for the rational design of novel therapeutic furin inhibitors toward anthrax and furin-dependent diseases 3.4.21.75 Furin drug development furin is considered a major target for intervention of cancer, tumorgenesis, viral and bacterial pathogenesis 3.4.21.75 Furin drug development furin inhibitors are promising therapeutics for the treatment of cancer and numerous infections caused by bacteria and viruses, including the highly lethal Bacillus anthracis or the pandemic influenza virus 3.4.21.75 Furin drug development the activation of viral glycoproteins by the host protease furin is an essential step in the replipation of numerous pathogenic viruses. Thus, effective inhibitors of furin can serve as broad-spectrum antiviral drugs, rational design of various types of cyclic inhibitors 3.4.21.75 Furin drug development the deglycosylated active recombinant enzyme can be used for structure-guided drug discovery 3.4.21.76 Myeloblastin drug development design of inhibitors aimed at neutralizing the cleavage activity of PR3 toward endogenous annexin 1 and hence suitable for development as novel anti-inflammatory therapeutics 3.4.21.76 Myeloblastin drug development optimized sequences, which allow close interaction with the extended active site of Pr3 for the development of peptide or pseudopeptide inhibitors that do not interfere with Pr3-related proteases 3.4.21.76 Myeloblastin drug development recombinant PR3 variants have a great potential to study individual anti-PR3 responses and will advance the development of new epitope-based therapeutics 3.4.21.76 Myeloblastin drug development either blocking the membrane presentation of PR3 or neutralizing the functions of its binding partners may generate novel therapeutic strategies for anti-neutrophil cytoplasmic autoantibodies-associated vasculitis 3.4.21.76 Myeloblastin drug development further exploration of the S' subsites of Pr 3 may lead to the identification of highly selective, reversible competitive inhibitors of Pr 3 using a functionalized surrogate scaffold embellished with appropriate recognition elements 3.4.21.76 Myeloblastin drug development enzyme inhibitors may prove to be targets for the generation of agents in the treatment of neutrophilic inflammatory disease 3.4.21.76 Myeloblastin drug development proteinase 3-inhibiting antibodies may play a role in autoimmune vasculitis and can be exploited as highly selective inhibitors 3.4.21.76 Myeloblastin drug development enzyme Pr3 is a target for the generation of agents in the treatment of neutrophilic inflammatory disease 3.4.21.77 semenogelase drug development compounds inhibiting the activity of prostate-specific antigen, prevent the anti-angiogenic effect of prostate-specific antigen in an angiogenesis model 3.4.21.77 semenogelase drug development STEAP is a good immunologic target antigen against prostate cancer and vaccination regimen successfully elicits anti-tumor CTL responses and suppresses tumor growth 3.4.21.77 semenogelase drug development development of PSA selective inhibitors as useful tools for the targeted treatment and imaging of prostate cancer 3.4.21.77 semenogelase drug development the gama-SM protein can be a drug target in prostate cancer therapy 3.4.21.83 Oligopeptidase B drug development Leishmania amazonensis OPB isozymes, OPB and OPB2, can be ideal drug targets to treat leishmaniasis, since both enzymes are expressed in all parasite lifecycle and are not identified in humans 3.4.21.88 Repressor LexA drug development the LexA repressor plays a key role in the induction of the SOS response and its importance in regulating responses to stress suggests that it may be exploited as a drug target 3.4.21.89 Signal peptidase I drug development type I signal peptidase is a potential target for the development of novel antibacterial agents 3.4.21.89 Signal peptidase I drug development bacterial type I signal peptidase is a potential target for the development of antibacterial agents 3.4.21.89 Signal peptidase I drug development in the search for antibacterial therapies, the type I signal peptidase serves as a potential target for development of antibacterials with another mode of action. SPase I is also is a feasible target for biofilm-associated infections 3.4.21.89 Signal peptidase I drug development SPase I is a target for development of inhibitors as antibiotics 3.4.21.89 Signal peptidase I drug development SPase I serves as a potentially interesting target for the development of antibacterials with another mode of action 3.4.21.89 Signal peptidase I drug development bacterial signal peptidase I (SPase) is a target for development of beta-lactam anti-bacterial inhibitors 3.4.21.89 Signal peptidase I drug development bacterial signal peptidase I (SPase) represents an attractive target in that SPase inhibitors exhibit broad-spectrum antibiotic activity, but even at sub-MIC doses also impair the secretion of essential virulence factors 3.4.21.90 Togavirin drug development alphavirus core protein is a target for antiviral chemotherapy 3.4.21.91 Flavivirin drug development characteristics of Yellow fever virus protease are very similar to those reported for dengue and West Nile virus proteases, and suggest that pan-flavivirus NS3 protease drugs may be developed for flaviviral diseases 3.4.21.91 Flavivirin drug development proteolysis through formation of a composite active site in NS2-3 protease occurs in the context of the viral polyprotein expressed in mammalian cells. This offers new opportunities for antiviral drug design 3.4.21.91 Flavivirin drug development switched cleavage preferences of West Nile virus NS2B-NS3(pro)teinase may provide valuable data for the design of optimized substrates and substrate-based selective inhibitors of flaviviral proteinases 3.4.21.91 Flavivirin drug development unique cleavage preferences of the Dengue virus protease promise novelty for the design of potent inhibitors that may be selective for the flaviviral proteases over proteases of the host cell and thus provide a solid base for follow-on structural and functional studies 3.4.21.91 Flavivirin drug development unique cleavage preferences of the West Nile virus protease promise novelty for the design of potent inhibitors that may be selective for the flaviviral proteases over proteases of the host cell and thus provide a solid base for follow-on structural and functional studies 3.4.21.91 Flavivirin drug development useful for the development of specific allosteric inhibitors designed to interfere with the productive interactions of NS2B with NS3pro 3.4.21.91 Flavivirin drug development flavivirus NS2B-NS3 protease-helicase is a target for antiviral drug development 3.4.21.91 Flavivirin drug development the dengue virus NS2B-NS3 protease (NS2B-NS3p) is an important antiviral target for drug development 3.4.21.91 Flavivirin drug development the enzyme is a target for the development of structure-based antiviral drugs against ZIKV and related pathogenic flaviviruses 3.4.21.91 Flavivirin drug development the enzyme is an important drug target 3.4.21.91 Flavivirin drug development the essential enzyme is a target for drug design 3.4.21.91 Flavivirin drug development the viral serine protease NS2B/NS3 is an attractive target for the development of anti-WNV agents 3.4.21.92 Endopeptidase Clp drug development synthetic beta-lactones as novel inhibitors for specific and selective targeting of the key virulence regulator ClpP 3.4.21.93 Proprotein convertase 1 drug development repression of proprotein convertase 1/3 by Pdcd4 may represent a novel mechanism for the function of Pdcd4 as a tumour suppressor 3.4.21.98 hepacivirin drug development characteristics of Yellow fever virus protease are very similar to those reported for dengue and West Nile virus proteases, and suggest that pan-flavivirus NS3 protease drugs may be developed for flaviviral diseases 3.4.21.98 hepacivirin drug development [1-[2-(2-carbamoyl-1-cyclobutylmethyl-2-oxo-ethylcarbamoyl)-6,6-dichloro-3-aza-bicyclo[3.1.0]hexane-3-carbonyl]-2,2-dimethyl-propyl]-carbamic acid tert-butyl ester is a lead for future SAR development 3.4.21.98 hepacivirin drug development barrier state B1 is a relevant molecular structure to be considered in the design of new inhibitors of the NS3 enzyme. Residues Arg-109, Lys-136, Gly-137, Arg-155 and Asp-79 are responsible for the electrostatic stabilization of B1. The tetra-coordinated intermediate I1, may also be of interest as possible targets for the design of new drugs 3.4.21.98 hepacivirin drug development combination with IFN-alpha with or without ribavirin may be a potential therapeutic strategy to suppress the emergence of Hepatitis C virus variants with substitutions at NS3 protease residue 155 3.4.21.98 hepacivirin drug development correct binding mode of 2-O-(4-O-galloylgalloyl)-1,3,4-tri-O-galloyl-beta-D-glucose can be used as a novel scaffold for anti-hepatitis C virus for the further reconstruction and design of new protease inhibitors 3.4.21.98 hepacivirin drug development design of epitope-based vaccines, where epitopes preferably should be those in which the virus is unable to mutate due to viral fitness 3.4.21.98 hepacivirin drug development genotype 1a, different catalytic efficiencies among NS3/4A proteases from different or similar hepatitis C virus genotypes. Because modulation of enzymatic activity of the protease is dependent on the interactions of a small number of NS4A amino acid residues, the design of small peptidomimetic protease inhibitors may be feasible 3.4.21.98 hepacivirin drug development genotype 1b, different catalytic efficiencies among NS3/4A proteases from different or similar hepatitis C virus genotypes. Because modulation of enzymatic activity of the protease is dependent on the interactions of a small number of NS4A amino acid residues, the design of small peptidomimetic protease inhibitors may be feasible 3.4.21.98 hepacivirin drug development genotype 3a, different catalytic efficiencies among NS3/4A proteases from different or similar hepatitis C virus genotypes. Because modulation of enzymatic activity of the protease is dependent on the interactions of a small number of NS4A amino acid residues, the design of small peptidomimetic protease inhibitors may be feasible 3.4.21.98 hepacivirin drug development genotype 4a, different catalytic efficiencies among NS3/4A proteases from different or similar hepatitis C virus genotypes. Because modulation of enzymatic activity of the protease is dependent on the interactions of a small number of NS4A amino acid residues, the design of small peptidomimetic protease inhibitors may be feasible 3.4.21.98 hepacivirin drug development genotype 4d, different catalytic efficiencies among NS3/4A proteases from different or similar hepatitis C virus genotypes. Because modulation of enzymatic activity of the protease is dependent on the interactions of a small number of NS4A amino acid residues, the design of small peptidomimetic protease inhibitors may be feasible 3.4.21.98 hepacivirin drug development nonpeptide inhibitors of hepatitis C virus NS3-SP from Chinese medicinal herb Rhodiola kirilowii (Regel) may serve as potential candiate anti-hepatitis C virus agents 3.4.21.98 hepacivirin drug development NS2B/NS3 protease crystal structure provides useful guidance in the drug discovery process for related Flavivirus proteases, given the large degree of homology within the family 3.4.21.98 hepacivirin drug development NS3 protease domain and minimal NS4A cofactor are sufficient to inhibit antiviral signaling through retinoic acid-inducible gene-I and melanoma differentiation-associated gene 5 and block activation of the downstream transcription factors interferon regulatory factor-3 and nuclear factor kappaB, accomplished by protease domain targeting and cleavage of interferon promoter stimulator-1. NS3-4A protease inhibitor therapy of hepatitis C virus infection can effectively remove the NS3-4A blockade to the innate immune response, restoring retinoic acid-inducible gene-I signaling to interferon promoter stimulator-1 and activation of IFN-stimulated gene expression in infected cells 3.4.21.98 hepacivirin drug development optimization of tetrapeptide substrates for enhanced protease affinity and processing efficiency provides important clues for developing inhibitors of West Nile Virus infection 3.4.21.98 hepacivirin drug development series of hepatitis C virus NS3 protease inhibitors comprising a trisubstituted cyclopentane N-acyl-(4R)-hydroxyproline mimic in the P2 position. The frequently used P2 hydroxyproline scaffold can successfully be displaced by a properly substituted cyclopentane scaffold. Further refinements of the compounds may provide even more effective hepatitis C virus NS3 protease inhibitors 3.4.21.98 hepacivirin drug development very potent NS3 protease inhibitors encompassing the 4-hydroxy-cyclopent-2-ene-1,2-dicarboxylic acid, a N-acyl-Lhydroxyproline mimic, in the P2-position. These inhibitors display two carboxy terminus where the P2 template induces a reversal of direction of the P3/P4 amino acid chain 3.4.21.98 hepacivirin drug development NS3 protease represents a drug target for treatment of HCV infections 3.4.21.98 hepacivirin drug development NS3 protease represents a drug target for treatment of HCV infections, development of inhibitors less sensitive to drug resistance, overview 3.4.21.98 hepacivirin drug development NS3/4A is a target for development of direct-acting antiviral agents (DAAs) targeting key viral enzymes essential for viral replication represents a significant milestone in the treatment of chronic HCV infection 3.4.21.98 hepacivirin drug development the epitopes B1, B8 and B9 are predicted to be ideal candidates for B-cell-based vaccine and are over 95% conserved across six major HCV genotypes. Determination of position and sequences of the peptides that may be used for development of peptide vaccines, overview 3.4.21.102 C-terminal processing peptidase drug development the enzyme is a target for development of herbicides 3.4.21.109 matriptase drug development the enzyme is a potential target in anti-cancer therapy 3.4.21.109 matriptase drug development matriptase-2 represents a target for the development of inhibitors, potentially useful in the treatment of hemochromatosis or beneficial as pharmacological tools 3.4.21.113 pestivirus NS3 polyprotein peptidase drug development binding mode of 2-O-(4-O-galloylgalloyl)-1,3,4-tri-O-galloyl-beta-D-glucose can be used as a scaffold for anti-HCV for the further reconstruction and design of new protease inhibitors 3.4.21.113 pestivirus NS3 polyprotein peptidase drug development nonpeptide inhibitors of NS3-SP from Chinese herbal medicine Rhodiola kirilowii may serve as potential candidate anti-hepatitis C virus agents. Cell viability and secreted alkaline phosphatase (SEAP) activity assays with the nonpeptide inhibitors of NS3-SP reveal little if any toxicity 3.4.22.1 cathepsin B drug development cathepsin B contributes to the neovascularization process and should be considered as a potential therapeutic target 3.4.22.1 cathepsin B drug development peptides containing Ala or Phe at positions 6 are good substrates for the enzyme at both pH 5.0 and 7.4. Those containing Glu, Asp, Lys or Val are not cleaved at all by cathepsin B at pH 7.4 and are poorly hydrolized at pH 5.0. These findings provide new information for the rational design of cathepsin B-activated peptide-containing anticancer drugs 3.4.22.1 cathepsin B drug development the new organotellurium(IV)compounds are powerful inhibitors of cathepsin B, constituting promising potential anti-metastatic agents 3.4.22.1 cathepsin B drug development cathepsin B could be a drug target for several pathologies, based mainly on its role in cancer progression and osteoarthritis in humans 3.4.22.1 cathepsin B drug development cathepsin B is a target for anticancer metallodrugs, inhibition of cathepsin B by antitumor ruthenium(II)-arene compounds, overview 3.4.22.1 cathepsin B drug development cathepsin B is a possible therapeutic target for the control of tumor progression 3.4.22.1 cathepsin B drug development cathepsin B is a target for development of efficient and specific inhibitors 3.4.22.1 cathepsin B drug development cathepsin B is a target for development of inhibitors to lower amyloid-beta protein in Alzheimer's disease 3.4.22.1 cathepsin B drug development the enzyme is a target for therapeutic inhibitors or vaccination 3.4.22.1 cathepsin B drug development cathepsin B is a target for anti-cancer therapy. RNA interference oligonucleotide shRNA-CTSB2 is the most efficient inhibition of cathepsin B at both mRNA and protein levels and results in suppressing endometrial cancer growth and development in vivo 3.4.22.15 cathepsin L drug development a clickable and tagless activity-based probe of cathepsin L probe is a highly effective tool in dissecting cathepsin L biology at the proteome levels in both normal physiology and human diseases, thereby facilitating drug-discovery efforts targeting cathepsin L 3.4.22.15 cathepsin L drug development cathepsins, including cathepsin L, are interesting targets for drug development in an effort to avoid parasite infection or reduce parasite burden and the pathogenic effects of the infection 3.4.22.27 cathepsin S drug development brain-penetrating cathepsin S inhibitors demonstrate potential clinical utility for the treatment of multiple sclerosis and neuropathic pain 3.4.22.27 cathepsin S drug development Cat S is an attractive therapeutic target and selective Cat S inhibitors may also modulate a number of other diseases such as rheumatoid arthritis, multiple sclerosis, myasthenia gravis, asthma, atherosclerosis and neuropathic pain 3.4.22.27 cathepsin S drug development cat S is an attractive therapeutic target for the treatment of autoimmune disorders 3.4.22.27 cathepsin S drug development CatS is an appropriate drug target in autoimmune disorders 3.4.22.27 cathepsin S drug development CatS is involved in the pathogenesis of autoimmune disorders, atherosclerosis and obesity, therefore, it represents a promising pharmacological target for drug development 3.4.22.27 cathepsin S drug development discovery of orally bioavailable cathepsin S inhibitors for the reversal of neuropathic pain, cathepsin S inhibitors are attractive targets as immunological therapeutic agents 3.4.22.27 cathepsin S drug development enzyme may be a potential target in rheumatoid arthritis and obesity with its associated cardiovascular risks 3.4.22.27 cathepsin S drug development importance of CATS in inflammatory processes, which has generated much interest in the development of CATS inhibitors as immunomodulatory therapeutics for immune disorders such as bronchial asthma, rheumatoid arthritis and psoriasis, CATS may also be an attractive target in neurodegenerative disorders associated with inflammation 3.4.22.27 cathepsin S drug development important role for cathepsin S in the regulation of ozone-induced airway hyperresponsiveness and neutrophil cell recruitment, cathepsin S may be a target in the treatment of oxidative stress-induced airway hyperresponsiveness and inflammation 3.4.22.27 cathepsin S drug development increased risk of mortality and morbidity associates with cardiovascular calcification drives the development of new therapeutic strategies to prevent and potentially reverse this process, new therapeutic options may also include selective inhibition of catS 3.4.22.27 cathepsin S drug development inhibition of the proteolytic activity of cathepsin S is an attractive target for drug development with such inhibitors having potential for modulation and regulation of autoimmune diseases such as multiple sclerosis and rheumatoid arthritis, and allergic disorders, such as asthma 3.4.22.28 picornain 3C drug development 3Cpro as the molecular target to develop anti enterovirus 71 agents 3.4.22.28 picornain 3C drug development three-dimensional pharmacophore models for peptidic and small organic nonpeptidic inhibitors of the human rhinovirus 3C protease, structure-based and ligand-based approach, using the software package Catalyst 3.4.22.28 picornain 3C drug development 3C protease inhibitors as anti-enterovirus anti-EV71 agents 3.4.22.28 picornain 3C drug development 3CP is an optimal target for the development of anti-viral agents 3.4.22.28 picornain 3C drug development the conserved key site of the enzyme may serve as attractive target for the design of broad-spectrum antivirals for multiple viruses in the supercluster 3.4.22.28 picornain 3C drug development 3C protease is regarded as an attractive target for the treatment of HRV infections 3.4.22.30 Caricain drug development caricain would be suitable for enzyme therapy in gluten intolerance and appears to have synergistic action with porcine intestinal extracts, potential for enzyme therapy in coeliac disease 3.4.22.B30 calpain 10 drug development the development of inhibitors against calpain-10 may be useful as therapeutic agents for a number of calpainopathies 3.4.22.34 Legumain drug development enzyme serves as a promising candidate for prodrug tumor therapy 3.4.22.37 gingipain R drug development potential target for the development of an anti-periodontitis vaccination 3.4.22.38 cathepsin K drug development Cat K inhibitors might be useful for the treatment of osteoporosis 3.4.22.38 cathepsin K drug development Cat S is an attractive therapeutic target and selective Cat S inhibitors may also modulate a number of other diseases such as rheumatoid arthritis, multiple sclerosis, myasthenia gravis, asthma, atherosclerosis and neuropathic pain 3.4.22.38 cathepsin K drug development cathepsin K inhibitors are regarded as a potential therapy for the treatment of bone loss, such as osteoporosis 3.4.22.38 cathepsin K drug development cathepsin K is seen as an attractive target for intervention in the treatment of both osteoporosis and osteoarthritis 3.4.22.38 cathepsin K drug development development of cathepsin K inhibitors as an approach for bone diseases with enhanced bone resorption 3.4.22.38 cathepsin K drug development lysosomal cysteine protease is an interesting target molecule with therapeutic potential to attenuate bleomycin-induced pulmonary fibrosis in mice 3.4.22.38 cathepsin K drug development the enzyme is a drug target in the treatment of osteoporosis 3.4.22.46 L-peptidase drug development the enzym eis a target for inhibitor design for inhibition of viral replication 3.4.22.B50 papain-like proteinase 2 drug development the enzyme is an attractive antiviral drug target because it is essential for coronaviral replication. Targeting the enzyme with antiviral drugs may have an advantage in not only inhibiting viral replication but also inhibiting the dysregulation of signaling cascades in infected cells that may lead to cell death in surrounding, uninfected cells 3.4.22.51 cruzipain drug development cruzipain is an attractive target for the development of novel trypanocidal drugs 3.4.22.56 caspase-3 drug development the VHH proteins, isolated from heavy chain antibody variable domain, i.e. VHH phage display library, are antagonist and agonist of apoptosis and could have potential for the development of therapeutics for neurodegenerative diseases and cancer, respectively 3.4.22.56 caspase-3 drug development caspase-3 ia a target for structure-based drug design approach 3.4.22.59 caspase-6 drug development selective inhibitors of caspase-6 may have therapeutic potential for various neurodegenerative disorders 3.4.22.59 caspase-6 drug development the enzyme is a target for therapeutic intervention in Alzheimer's and Huntington's diseases 3.4.22.61 caspase-8 drug development gastric cancer might be a good target of TRAIL therapy because the majority of tumor cells have intact caspase-8 expression. The anticancer efficacy may be predicted by the degree of caspase-8 activation after TRAIL treatment 3.4.22.61 caspase-8 drug development caspase-8 ia a target for structure-based drug design approach 3.4.22.B62 cathepsin L3 drug development cathepsin L3 is a protease that plays important roles during the life cycle of fluke. Due to its particular collagenolytic activity it is considered an attractive drug target in the infective phase of Fasciola hepatica 3.4.22.65 peptidase 1 (mite) drug development the enzyme is a target for design and development of specific inhibitors for treatment of allergic asthma 3.4.22.66 calicivirin drug development the conserved key site of the enzyme may serve as attractive target for the design of broad-spectrum antivirals for multiple viruses in the supercluster 3.4.22.69 SARS coronavirus main proteinase drug development coronavirus main protease (M(pro)) represents an attractive drug target for antiviral therapy of coronavirus infections, including severe acute respiratory syndrome (SARS) 3.4.22.69 SARS coronavirus main proteinase drug development the enzyme is an attractive target for the development of anti-SARS drugs 3.4.22.70 sortase A drug development the enzyme is a bona fide drug target 3.4.22.70 sortase A drug development the enzyme is is a promising target for therapies against Gram-positive bacteria, in general, and staphylococci, in particular 3.4.22.B70 SENP1 peptidase drug development SENP1 is a potential therapeutic target for the treatment of prostate cancers 3.4.22.B70 SENP1 peptidase drug development SENP1 is an essential gene and is a potential target for developing therapeutic agents for cancer 3.4.22.B70 SENP1 peptidase drug development the enzyme is a drug target for development of small molecule drugs against prostate cancer 3.4.22.B79 nsP2 protease drug development alphavirus nsp2pro proteases are not very useful tools for the removal of affinity tags from recombinant proteins although they do remain promising therapeutic targets for the treatment of a variety of diseases 3.4.22.B80 SARS-CoV papain-like protease drug development chemical-informatics approach to COVID-19 drug discovery. Monte Carlo based QSAR, virtual screening and molecular docking study of some in-house molecules as papain-like protease inhibitors 3.4.22.B80 SARS-CoV papain-like protease drug development inhibition of SCoV2-PLpro with GRL-0617 impairs the virus-induced cytopathogenic effect, fosters the anti-viral interferon pathway and reduces viral replication in infected cells. These results highlight a dual therapeutic strategy in which targeting of SCoV2-PLpro can suppress SARS-CoV-2 infection and promote anti-viral immunity 3.4.22.B80 SARS-CoV papain-like protease drug development inhibitors of papain-like protease show promising results as an antiviral therapy in vitro. A list of inhibitors is reported that suggests possible therapeutic strategies for COVID-19 treatment, using both clinical and preclinical drugs 3.4.22.B80 SARS-CoV papain-like protease drug development naphthalene PLpro inhibitors designed for SARS-CoV can inhibit SARSCoV-2 PLpro as well as impede SARS-CoV-2 replication 3.4.22.B80 SARS-CoV papain-like protease drug development SARS-CoV-2 papain like protease is an important anti-virus drug target protein for the development of small-molecule inhibitors 3.4.22.B80 SARS-CoV papain-like protease drug development SARS-CoV-2 papain-like protease (PLpro) is used to virtually screen 1697 clinical Food and Drug Administration-approved drugs. Among the top results expected to bind with SARS-CoV-2 PLpro strongly are three cell protectives and antioxidants (NAD+, quercitrin, and oxiglutatione), three antivirals (ritonavir, moroxydine, and zanamivir), two antimicrobials (doripenem and sulfaguanidine), two anticancer drugs, three benzimidazole anthelmintics, one antacid (famotidine), three anti-hypertensive ACE receptor blockers (candesartan, losartan, and valsartan) and other miscellaneous systemically or topically acting drugs. The binding patterns of these drugs are superior to the SARS CoV PLpro inhibitor, 6-mercaptopurine, suggesting a potential for repurposing these drugs to treat COVID-19. The ten drugs with the highest estimated docking scores with favorable pharmacokinetics are subjected to molecular dynamics simulations followed by molecular mechanics/generalized Born surface area binding energy calculations. Phenformin, quercetin, and ritonavir all demonstrated prospective binding affinities for SARS-CoV-2 papain-like protease over 50 ns MD simulations, with binding energy values of -56.6, -40.9, and -37.6 kcal/mol, respectively. Energetic and structural analyses show phenformin is more stable than quercetin and ritonavir. The list of the drugs provided constitutes a primer for clinical application in COVID-19 patients and guidance for further antiviral studies 3.4.22.B80 SARS-CoV papain-like protease drug development synergistic inhibition of the enzyme by disulfiram and 6-thioguanine or mycophenolic acid implies the potential for combination treatments using these three clinically available drugs 3.4.22.B80 SARS-CoV papain-like protease drug development virtual screening-driven drug discovery of SARS-CoV2 enzyme inhibitors targeting viral attachment, replication, post-translational modification and host immunity evasion infection mechanisms. Scedapin C, quinadoline B, norquinadoline A, isochaetochromin D1 and 11alpha-dehydroxyisoterreulactone A exhibit high binding affinities on papain-like protease. Molecular dynamics simulation and subsequent totalfree energy calculation reveal that the complexes formed between the top-ranked ligands and their respective protein targets are dynamically stable with high total free energy of binding. Therefore, these compounds can be utilized as templates or prototypes for further development of multitargeting ligands against SARS-CoV2 3.4.22.B80 SARS-CoV papain-like protease drug development the enzyme represents a highly promising target for the development of antiviral drugs 3.4.23.B4 Feline immunodeficiency virus protease drug development the enzyme is a model target for development of inhibitors due to its similarity with the HIV-1 retropepsin, overview 3.4.23.B8 human T-cell leukemia virus type 1 protease drug development enzyme HTLV-1 PR enzyme is an attractive drug target for anti-cancer drug design and treatment, structure-based drug discovery, overview 3.4.23.16 HIV-1 retropepsin drug development the enzyme is a target for drug development 3.4.23.45 memapsin 1 drug development therapeutic interventions that potentiate BACE2 may prevent Alzheimer’s disease 3.4.23.47 HIV-2 retropepsin drug development HIV-2 protease is an important drug target 3.4.24.B4 matrix metalloproteinase-13 drug development the enzyme is a target for design of tetracycline-based drugs 3.4.24.7 interstitial collagenase drug development MMP-1 enzyme inhibitor astragaloside IV is a potential agent against skin photoaging 3.4.24.17 stromelysin 1 drug development human enzyme MMP-3, i.e. stromelysin-1, is an anti-cancer drug target 3.4.24.23 matrilysin drug development andrographolide is a chemotherapeutic agent due to its ability of inhibiting tumor cell proliferation and inflammation by e.g. supprressing MMP-7 3.4.24.23 matrilysin drug development matrilysin is an ideal biological target to developl inhibitors because it is overexpressed in malignant tumour cells 3.4.24.35 gelatinase B drug development MMP-9 is a target for therapeutic treatment 3.4.24.35 gelatinase B drug development MMP-9 is a therapeutic target in autoimmune diseases, vascular pathologies, and cancer 3.4.24.35 gelatinase B drug development MMP-9 is an attractive target for therapeutic intervention studies in mouse models 3.4.24.57 O-sialoglycoprotein endopeptidase drug development Gcp may be a target for developing antibacterial agents 3.4.24.63 meprin B drug development the astacin protease meprin beta is an emerging drug target for treatment of disorders such as kidney failure, fibrosis or inflammatory bowel disease 3.4.24.65 macrophage elastase drug development the enzyme is a target for drug development 3.4.24.65 macrophage elastase drug development the enzyme is a target in treatment of degradative disease processes in the skin 3.4.24.69 bontoxilysin drug development the enzyme is a target for design of specific inhibitors 3.4.24.69 bontoxilysin drug development because of the potential for use of the toxin in bioterrorism and the increasingly widespread application of the toxin in the medical field, there is interest in the development of small-molecule inhibitors of the metalloprotease 3.4.24.69 bontoxilysin drug development botulinum toxins are targets for rational development of preventive vaccines or inhibitors 3.4.24.69 bontoxilysin drug development ability of monoclonal antibodies F1-2 and F1-40 to provide therapeutic protection against BoNT/A intoxication in mouse intravenous and oral intoxication models, overview 3.4.24.69 bontoxilysin drug development RNA aptamers are a unique group of molecules acting as therapeutics and as an antidote against botulism 3.4.24.69 bontoxilysin drug development the BoNT/A Lc alpha-exosite is a target for inhibitor development 3.4.24.69 bontoxilysin drug development the botulinum toxin is a target for development of specific drugs to treat botulism 3.4.24.69 bontoxilysin drug development the toxin is a target for development of inhibitors to treat muscular paralysis, and of drugs altering BoNT/B light chain ubiquitination to overcome botulinum persistence in neuronal cells 3.4.24.71 endothelin-converting enzyme 1 drug development the enzyme is a target for drug design in cardiovascular disease 3.4.24.71 endothelin-converting enzyme 1 drug development ECE-1 is a potential target for the treatment of Alzheimer’s disease based on its role in amyloid-beta peptide degradation 3.4.24.71 endothelin-converting enzyme 1 drug development ECE-1 silencing (RNAi) may be a promising ovarian carcinoma anticancer therapy 3.4.24.71 endothelin-converting enzyme 1 drug development Inhibition of endothelin-1 production by ECE-1 is a promising target for the treatment of cardiovascular disease, but lack of substrate specificity is disadvantageous since inhibition of ECE-1 has impact on other pathways too 3.4.24.71 endothelin-converting enzyme 1 drug development mixed ACE/ECE-1 inhibitor may lead to vasopeptide inhibitors that can reduce the levels of angiotensin-II and endothelin-1, without interfering with bradykinin cleavage 3.4.24.72 fibrolase drug development summary of results (including adverse events and pharmacodynamics) regarding drug development of alfimeprase as a potential drug against thrombosis and vascular disorders 3.4.24.80 membrane-type matrix metalloproteinase-1 drug development MMP-14 is an effective therapeutic target in therapy of mesothelioma tumours 3.4.24.80 membrane-type matrix metalloproteinase-1 drug development dimeric MT1-MMP inhibitors might be further developed and exploited as an alternative tool to reduce cancer cell invasion 3.4.24.87 ADAMTS13 endopeptidase drug development inhibitory anti-ADAMTS 13 antibodies, measurement and clinical application, overview 3.4.25.1 proteasome endopeptidase complex drug development the proteasome is a target for inhibitor development and optimization, overview 3.5.1.4 amidase drug development the enzyme may be another attractive drug target 3.5.1.B4 acetylcitrulline deacetylase drug development possible target for drugs 3.5.1.5 urease drug development 3-,6-,7-,9-,12-monohydroxy tetradecanoic acid isomers can be used in agriculture, pharmacy and cosmetic industries due to their excellent antielastase, antiurease and antioxidant activities. Hydroxy fatty acids can be urease inhibitors and anti-Helicobacter pylori agents due to their antiurease activity 3.5.1.5 urease drug development urease is considered a first line target for drug development and vaccination against Helicobacter pylori infection 3.5.1.18 succinyl-diaminopimelate desuccinylase drug development protein may be potential target for developing a vaccine against Leishmania infantum 3.5.1.18 succinyl-diaminopimelate desuccinylase drug development development of antimicrobial agents that target DapE 3.5.1.19 nicotinamidase drug development enzyme is involved in the activation of the antituberculosis drug pyrazinamide 3.5.1.19 nicotinamidase drug development while nicotinamidases are widespread in nature they are not occuring within mammals and present a potential drug target. The enzymes can be used in the activation of tuberculosis prodrugs such as pyrazinamide 3.5.1.23 ceramidase drug development development of small molecule drugs, that inhibit AC enzyme activity, is a promising approach for improving standard cancer therapy and patient's clinical outcomes 3.5.1.24 choloylglycine hydrolase drug development the broad substrate specificity nature of Lactobacillus salivarius enzyme may make it an ideal candidate for screening desired BSH inhibitors targeting various BSH enzymes 3.5.1.24 choloylglycine hydrolase drug development the enzyme is a target for BSH inhibitor development, overview 3.5.1.25 N-acetylglucosamine-6-phosphate deacetylase drug development NagA is a potential antitubercular drug target because it represents the key enzymatic step in the generation of essential amino-sugar precursors required for Mtb cell wall biosynthesis and also influences recycling of cell wall peptidoglycan fragments 3.5.1.28 N-acetylmuramoyl-L-alanine amidase drug development the enzyme is a potential drug target 3.5.1.28 N-acetylmuramoyl-L-alanine amidase drug development the enzyme can aid in the development of cell wall targeting therapeutics against Mycobacterium tuberculosis 3.5.1.28 N-acetylmuramoyl-L-alanine amidase drug development a thermophilic phage endolysin fusion to a Clostridium perfringens-specific cell wall binding domain creates an anti-Clostridium antimicrobial with improved thermostability, overview 3.5.1.38 glutamin-(asparagin-)ase drug development enzyme could possibly be used as an anti-tumor therapeutic agent 3.5.1.41 chitin deacetylase drug development the isozyme might be a good drug target 3.5.1.48 acetylspermidine deacetylase drug development HDAC10 is a biomarker and a target for the design of isozyme-selective inhibitors that will suppress autophagic responses to cancer chemotherapy, thereby rendering cancer cells more susceptible to cytotoxic drugs 3.5.1.60 N-(long-chain-acyl)ethanolamine deacylase drug development the enzyme is a target for drug design 3.5.1.60 N-(long-chain-acyl)ethanolamine deacylase drug development inhibitors against N-acylethanolamine-hydrolyzing acid amidase are promising tools against bladder cancer 3.5.1.60 N-(long-chain-acyl)ethanolamine deacylase drug development NAAA is a promising target for the development of effective and safe treatments for atopic dermatitis and other inflammatory disorders of the skin 3.5.1.60 N-(long-chain-acyl)ethanolamine deacylase drug development the cysteine hydrolase, N-acylethanolamine acid amidase (NAAA) is a promising target for analgesic and anti-inflammatory drugs 3.5.1.88 peptide deformylase drug development potential target or the development of new antibacterial agents 3.5.1.88 peptide deformylase drug development human peptide deformylase (HsPDF) is an important target for anticancer drug discovery 3.5.1.88 peptide deformylase drug development peptide deformylase (PDF) is considered an excellent target to develop antibiotics 3.5.1.88 peptide deformylase drug development peptide deformylase (PDF), a metalloprotease, is an important antibacterial drug target 3.5.1.88 peptide deformylase drug development the enzyme HsPDF is a cancer therapeutic target 3.5.1.88 peptide deformylase drug development the enzyme is a drug target for antibacterial agents. Classification of PDF inhibitors, overview 3.5.1.88 peptide deformylase drug development the enzyme is a drug target in malaria treatment 3.5.1.88 peptide deformylase drug development the enzyme is an important antibacterial drug target 3.5.1.88 peptide deformylase drug development the enzyme is an important target to develop antibacterial agents 3.5.1.89 N-acetylglucosaminylphosphatidylinositol deacetylase drug development the enzyme is a target in the treatment of African sleeping sickness 3.5.1.92 pantetheine hydrolase drug development the highly sensitive fluorescent assay for the hydrolysis of pantothenate-7-amido-4-methylcoumarin as substrate to pantothenic acid and 7-amino-4-methylcoumarin could be a powerful tool for target validation and drug lead identification and characterization 3.5.1.97 acyl-homoserine-lactone acylase drug development therapeutic efficacy of PvdQ acylase as a quorum quenching agent during Pseudomonas aeruginosa infection (mouse model of pulmonary Pseudomonas aeruginosa infection) 3.5.1.98 histone deacetylase drug development the enzyme might be a promising target for the development of novel anti-babesial drugs 3.5.1.99 fatty acid amide hydrolase drug development FAAH is an attractive target for treating pain 3.5.1.103 N-acetyl-1-D-myo-inositol-2-amino-2-deoxy-alpha-D-glucopyranoside deacetylase drug development enzyme MshB is a target for the discovery of drugs to treat tuberculosis 3.5.1.108 UDP-3-O-acyl-N-acetylglucosamine deacetylase drug development enzyme is an attractive target against Pseudomonas infection 3.5.1.108 UDP-3-O-acyl-N-acetylglucosamine deacetylase drug development lipid A is an essential component of the outer membranes of most Gram-negative bacteria, making LpxC an attractive target for antibiotic design 3.5.1.108 UDP-3-O-acyl-N-acetylglucosamine deacetylase drug development LpxC is a target for the development of antimicrobial agents in the treatment of Gram negative infections 3.5.1.108 UDP-3-O-acyl-N-acetylglucosamine deacetylase drug development LpxC represents a highly attractive target for a novel antibacterial drug 3.5.1.108 UDP-3-O-acyl-N-acetylglucosamine deacetylase drug development target for development of anti-infective drugs against gram-negative bacteria 3.5.1.108 UDP-3-O-acyl-N-acetylglucosamine deacetylase drug development the enzyme is a promising target for antibacterial drug development, structure-guided drug discovery of broad spectrum Gram-negative antibiotics 3.5.1.108 UDP-3-O-acyl-N-acetylglucosamine deacetylase drug development the enzyme is a target for antibiotic therapy and structure-based drug design 3.5.1.119 Pup amidohydrolase drug development the Pup-proteasome enzymes are essential for full virulence and persistence in the mammalian host. As such, the Pup-proteasome enzymes are potential targets for development of antituberculosis therapeutics. Such development requires sensitive and robust assays for measurements of enzymatic activities and the effect of examined inhibitors. An in vitro activity assay for Dop, the first enzyme in the Pup-proteasome system is described, that is ased on fluorescence anisotropy measurements. This assay is simple, sensitive, and compatible with a high-throughput format for screening purposes and can be reliably and conveniently used for detailed kinetic measurements of Dop activity 3.5.1.124 protein deglycase drug development secreted DJ-1 levels in serum and DJ-1-binding compounds will be a diagnostic biomarker and therapeutic drug for neurodegenerative diseases 3.5.2.B2 (+)-gamma-lactamase drug development application of the enzyme in antiviral drug synthesis. The enzyme catalyzes the specific hydrolysis of (+)-gamma-lactam out of the racemic gamma-lactam (2-azabicyclo[2.2.1]hept-5-en-3-one) to leave optically pure (-)-gamma-lactam, which is the key building block of antiviral drugs such as carbovir and abacavir 3.5.2.B2 (+)-gamma-lactamase drug development the enzyme can be a promising candidate of biocatalyst for industrial applications of highly valuable chiral pharmaceutical chemicals 3.5.2.B2 (+)-gamma-lactamase drug development the enzyme is an ideal catalyst for the preparation of carbocyclic nucleosides of pharmaceutical interest. IT can be used in a scalable bioprocess and is an efficient, economical, and environmentally route for producing optically pure (-)-gamma-lactam 3.5.2.B2 (+)-gamma-lactamase drug development the use of gamma-lactamase as a biocatalyst offers an attractive and environmentally friendly approach for the synthesis of a broad range of carbocyclic nucleoside drugs. The enzyme can be used for enzymatic kinetic resolution of racemic Vince lactam (2-azabicyclo[2.2.1]hept-5-en-3-one) in the industry. Optically pure enantiomers and their hydrolytic products are widely employed as key chemical intermediates for developing a wide range of carbocyclic nucleoside medicines, including US FDA-approved drugs peramivir and abacavir 3.5.2.3 dihydroorotase drug development the essential enzyme is a target for antibacterial drug design 3.5.2.3 dihydroorotase drug development the substantial difference between bacterial and mammalian DHOs makes the bacterial enzyme a promising drug target for disrupting bacterial growth and thus an important candidate to evaluate as a response to antimicrobial resistance on a molecular level 3.5.2.6 beta-lactamase drug development the enzyme is a target for treatment of Mycobacterium abscessus infections 3.5.2.6 beta-lactamase drug development ZINC01807204 might be useful as a lead molecule for further optimization and development of more potent non beta-lactam inhibitors against KPC-2 3.5.2.6 beta-lactamase drug development enzyme BlaC is a rational enzyme target for therapeutic agents in treatment of tuberculosis caused by Mycobacterium tuberculosis 3.5.2.6 beta-lactamase drug development the PWP triad is an evolutionarily conserved motif unique to class A beta-lactamases aligning its allosteric site and hence is an effective potential target for enzyme regulation and selective drug design 3.5.3.1 arginase drug development the application of rhArg-PEG alone or in combination with existing chemotherapeutic drugs may represent a specific and effective therapeutic strategy against human hepatocellular carcinoma 3.5.3.1 arginase drug development arginase catalyzes the first committed step in the biosynthesis of polyamines that enable cell growth and hence potential drug target for the treatment of leishmaniasis 3.5.3.6 arginine deiminase drug development ADI is a potential anti-tumor drug for the treatment of argine-auxotrophic tumors, e.g. hepatocellular carcinoma and melanoma 3.5.3.6 arginine deiminase drug development anti-tumor drug 3.5.3.6 arginine deiminase drug development arginine deiminase is a therapeutic protein for cancer therapy of arginine-auxotrophic tumors. An ammonia detection-based screening system for arginine deiminase activity improvement at low arginine concentrations is developed and validated by identifying variants of the Pseudomonas plecoglossicida arginine deiminase with improved activity at physiological arginine concentrations. Four amino acid substitutions are identified to reduce S0.5 values or increase kcat values. The antiproliferation activity of the improved enzyme variant K30R/C37R/L148P/V291L is investigated and compared to wild-type and mutant enzyme K5T/D38H/D44E/A128T/E296K/H404R by in vitro experiments with two relevant melanoma cell lines under physiological conditions. Pseudomonas plecoglossicida arginine deiminase variant K30R/C37R/L148P/V291L is a highly attractive candidate to be used as therapeutic protein for the treatment of arginine-auxotrophic melanomas 3.5.3.6 arginine deiminase drug development L-arginine deiminase has a powerful anticancer activity against various tumors, via arginine depletion, arresting the cell cycle at G1 phase. The free and PEGylated enzyme exhibits a similar cytotoxic efficacy against HCT, HEP-G2, and MCF7 cells, lower than the cytotoxic efficacy of to enzyme covalently immobilized on dextran. The in vitro anticancer activity of the enzyme against HCT, MCF7, and HEPG-2 cells is increased by five-, three-, and threefold upon covalent modification by dextran 3.5.3.6 arginine deiminase drug development possibility of a use of the enzyme as a potential anticancer drug. Purified enzyme exhibits profound antiproliferative activity against Hep-G2 cells. Purified enzyme induces apoptosis in the Hep-G2 cells by DNA fragmentation 3.5.3.6 arginine deiminase drug development the enzyme is a particularly attractive therapeutic target for breast cancer because it is recruited by the estrogen receptor to endoplasmic reticulum target gene promoters where it citrullinates histone H3 at R26, leading to ER-target gene activation 3.5.3.6 arginine deiminase drug development the enzyme shows potential anticancer activity against various arginine-auxotrophic tumors. The higher antigenicity, structural instability and in vivo proteolysis are the major challenges that limit this enzyme from further clinical implementation. The anticancer activity of the enzyme to breast (MCF-7), liver (HepG-2) and colon (HCT8, HT29, DLD1 and LS174 T) cancer cell lines is increased by 1.7folds with dextran conjugation in vitro. Pharmacokinetically, the half-life time of ADI is increased by 1.7folds upon dextran conjugation, in vivo. From the biochemical and hematological parameters, arginine deiminase has no signs of toxicity to the experimental animals 3.5.3.6 arginine deiminase drug development the lack of this enzyme in the human host makes arginine deiminase an attractive target for drug design against Giardia intestinalis 3.5.3.12 agmatine deiminase drug development Campylobacter jejuni agmatine deiminase is a potentially important target for combatting antibiotic resistance 3.5.3.15 protein-arginine deiminase drug development PAD4 is a leading target for the development of a rheumatoid arthritis pharmaceutical 3.5.3.15 protein-arginine deiminase drug development the enzyme is a particularly attractive therapeutic target for breast cancer because it is recruited by the estrogen receptor to endoplasmic reticulum target gene promoters where it citrullinates histone H3 at R26, leading to ER-target gene activation 3.5.4.3 guanine deaminase drug development because these enzymes play an important role in nucleotide metabolism, they are relevant targets in anticancer and antibacterial therapies 3.5.4.4 adenosine deaminase drug development enzyme inhibitor FR234938 might be effective as an anti-rheumatic and anti-inflammatory drug by modulating the host-defense concentrations of adenosine 3.5.4.4 adenosine deaminase drug development adenosine deaminase inhibitors have potential as anti-inflammatory drugs or immunosuppressants 3.5.4.4 adenosine deaminase drug development because these enzyme plays an important role in nucleotide metabolism, they are relevant targets in anticancer and antibacterial therapies 3.5.4.4 adenosine deaminase drug development Plasmodium parasites lack enzymes critical for de novo purine synthesis and thus rely on purine salvage to supply precursors for nucleic acid synthesis and energy metabolism. Thus, the purine salvage pathway is an attractive drug target 3.5.4.4 adenosine deaminase drug development progesterone treatment may prevent epileptic activity by decreasing adenosine deaminase levels 3.5.4.5 cytidine deaminase drug development CDA is a target for development of specific enzyme inhibitors with potential anti-proliferative activity on cell growth of Mycobacterium tuberculosis, the major causative agent of tuberculosis 3.5.4.9 methenyltetrahydrofolate cyclohydrolase drug development the bifunctional enzyme is a target for design of parasite-specific inhibitors as structure-based drugs 3.5.4.10 IMP cyclohydrolase drug development the enzyme is a potential target for antineoplastic intervention, design of IMPCH inhibitors, overview 3.5.4.10 IMP cyclohydrolase drug development the enzyme is an important drug target 3.5.4.19 phosphoribosyl-AMP cyclohydrolase drug development the enzyme is identified as drug target. Brucella melitensis is a pathogenic gram-negative bacterium which is known for causing zoonotic diseases (Brucellosis). The organism is highly contagious and is used as bioterrorism agent against humans 3.5.4.37 double-stranded RNA adenine deaminase drug development ADAR1 is a potential therapeutic target in a subset of cancers 3.5.4.37 double-stranded RNA adenine deaminase drug development the enzyme (ADAR1) promotes the Zika virus replication by inhibiting the activation of protein kinase PKR. The enzyme can be a potential target of antiviral drugs 3.6.1.5 apyrase drug development Ecto-NTPDase1 is a target candidate in chemotherapy of Chagas disease 3.6.1.5 apyrase drug development the NTPDase isozymes are targets for development of potent and selective drug-like NTPDase inhibitors 3.6.1.9 nucleotide diphosphatase drug development NPP1 has been proposed as a drug target for the treatment of glioblastoma 3.6.1.12 dCTP diphosphatase drug development the enzyme is a drug target 3.6.1.12 dCTP diphosphatase drug development DCTPP1 counteracts the cytotoxic effect of the antitumoral demethylating agent decitabine (5-aza-deoxycytidine) by removing 5-aza-dCTP from the nucleotide pool and is being studied as a potential drug target to improve decitabine-based chemotherapy 3.6.1.12 dCTP diphosphatase drug development the enzyme is a factor involved in the mode of action of decitabine with potential value as enzymatic targets to improve decitabine-based chemotherapy 3.6.1.23 dUTP diphosphatase drug development dUTPase as a platform for antimalarial drug design: structural basis for the selectivity of a class of nucleoside inhibitors 3.6.1.23 dUTP diphosphatase drug development induced fit drug design 3.6.1.23 dUTP diphosphatase drug development inhibitor development against the enzyme can be useful in antiviral and anticancer therapy 3.6.1.23 dUTP diphosphatase drug development the enzyme is a potential antiparasitic drug target 3.6.1.23 dUTP diphosphatase drug development the enzyme might be a target for drug development 3.6.1.23 dUTP diphosphatase drug development dUTPase is a promising antituberculotic drug target 3.6.1.23 dUTP diphosphatase drug development the enzyme is a target for development of antimicrobial agents 3.6.1.23 dUTP diphosphatase drug development the nuclear isoform of the enzyme is a target for anticancer chemotherapeutic strategies 3.6.1.23 dUTP diphosphatase drug development dUTPase family of enzymes are promising targets for anticancer and antimicrobial therapies 3.6.1.23 dUTP diphosphatase drug development the enzyme is a potential drug target against malaria 3.6.1.23 dUTP diphosphatase drug development the enzyme is a target for anti-malarial drugs 3.6.1.23 dUTP diphosphatase drug development the enzyme is a target for development of therapeutic drugs against EBV infection 3.6.1.23 dUTP diphosphatase drug development the enzyme is a target for drugs against campylobacteriosis 3.6.1.23 dUTP diphosphatase drug development the enzyme is a factors involved in the mode of action of decitabine with potential value as enzymatic targets to improve decitabine-based chemotherapy 3.6.1.31 phosphoribosyl-ATP diphosphatase drug development because of its essentiality for growth in vitro, HisE is a potential drug target for tuberculosis 3.6.4.10 non-chaperonin molecular chaperone ATPase drug development Hsp70 proteins are targets for the drug-based treatments for cancers, misfolding diseases, and protein folding disorders 3.6.4.10 non-chaperonin molecular chaperone ATPase drug development human heat shock protein 90 is a target in cancer drug discovery, inhibition of ATP hydrolysis is a validated avenue for the development of anticancer therapies 3.6.4.10 non-chaperonin molecular chaperone ATPase drug development reconstitution of the entire Plasmodium translocon of exported proteins, PTEX, to aid structure-based design of anti-malarial drugs 3.6.4.B10 chaperonin ATPase (protein-folding, protecting from aggregation, protein stabilizing) drug development development of cell-based CCT inhibitors using peptide reagents and HSF1A, a benzyl-pyrazole-based small molecule 3.6.4.B10 chaperonin ATPase (protein-folding, protecting from aggregation, protein stabilizing) drug development development of small-molecule inhibitors of TRiC as potential antiviral therapeutics 3.6.4.B10 chaperonin ATPase (protein-folding, protecting from aggregation, protein stabilizing) drug development the enzyme is a target for the specific treatments of AML1-ETO-positive leukemia. AML1-ETO suppression by small interfering RNAs (siRNAs) supports normal myeloid differentiation of t(8,21)-positive leukemic cells which highlights AML1-ETO as a major clinical target to treat AML. Inhibition of HSP70/90, two major proteostasis regulators, has shown antileukemic effects in AML1-ETO positive cells. Moreover, the mammalian cytosolic chaperonin TRiC (or CCT) modulates the synthesis, folding and activity of AML1-ETO by direct association, primarily through its DNA-binding domain (AML1-175), and that HSP70 promotes this interaction 3.6.4.13 RNA helicase drug development the enzyme is a target for anti-HCV drug development 3.6.4.13 RNA helicase drug development the enzyme is a target for development of specific antiviral inhibitors 3.6.4.13 RNA helicase drug development the multifunctional NS3 protein from Dengue virus is a target for the design of antiviral inhibitors 3.6.4.13 RNA helicase drug development enzyme p68 is a drug target in the treatment of cancer, e.g. breast cancer 3.6.5.1 heterotrimeric G-protein GTPase drug development mutants of transducin represent a major tool in designing potential therapeutical strategies for a group of visual diseases 3.6.5.2 small monomeric GTPase drug development the enzyme Der may be an ideal cellular target against which antibiotics can be developed, lead compounds inhibiting Der GTPase provide scaffolds for the development of antibiotics against antibiotic-resistant pathogenic bacteria 3.7.1.3 kynureninase drug development the enzym eis a target for the design of potent and/or selective inhibitors of bacterial kynureninase 3.7.1.3 kynureninase drug development the enzyme is a target for the design of potent and/or selective inhibitors of human kynureninase 3.10.1.1 N-sulfoglucosamine sulfohydrolase drug development the enzyme is a target for the development of structure-based drug design for the devastating neurodegenerative disorder mucopolysaccharidosis type IIIA or Sanfilippo A syndrome 3.13.2.1 adenosylhomocysteinase drug development because of the prominent role of SAM-dependent transmethylation in capped methylated structure production at the 5'-terminus of viral mRNA, SAHH inhibitors could be developed to be broad-spectrum antiviral agents 4.1.1.11 aspartate 1-decarboxylase drug development the enzyme is a target for structure-based drug development 4.1.1.11 aspartate 1-decarboxylase drug development the enzyme is a good drug target 4.1.1.11 aspartate 1-decarboxylase drug development the PanDZ complex is a target for antibiotic development 4.1.1.17 ornithine decarboxylase drug development the enzyme ODC is a drug target in human malignancies, such as skin cancer 4.1.1.17 ornithine decarboxylase drug development the enzyme of the parasite is a potential target for the development of new drugs for treatment of disease such as African sleeping sickness 4.1.1.17 ornithine decarboxylase drug development the enzyme of the parasite is a potential target for the development of new drugs for treatment of diseases such as African sleeping sickness or Chagas disease 4.1.1.17 ornithine decarboxylase drug development the enzyme of the parasite is a potential target for the development of new drugs for treatment of diseases such as African sleeping sickness or cutaneous leishmaniasis 4.1.1.17 ornithine decarboxylase drug development the enzyme of the parasite is a potential target for the development of new drugs for treatment of diseases such as African sleeping sickness or visceral leishmaniasis 4.1.1.17 ornithine decarboxylase drug development pharmacological inhibition of ODC is a promising therapeutic paradigm for the treatment of visceral and perhaps other forms of leishmaniasis 4.1.1.17 ornithine decarboxylase drug development the enzyme is a potential anticancer target for inhibitor development 4.1.1.17 ornithine decarboxylase drug development the ODC gene might act as a prognostic factor for breast cancer and it could be a promising therapeutic target for cancer research 4.1.1.17 ornithine decarboxylase drug development because ODC is essential for trypanothione biosynthesis, polyamines of parasitic protozoa may be potential targets for the development of drugs with activity against Leishmania donovani. One goal of drug development is to evaluate the potential of Leishmania antigen for evoking a Th1 response against Leishmania infection 4.1.1.19 arginine decarboxylase drug development the enzyme is an attractive target for drug design 4.1.1.19 arginine decarboxylase drug development the enzyme is a target for drug design 4.1.1.22 histidine decarboxylase drug development HDC is a potential target to attenuate histamine production in certain pathological states using structure-based inhibitors, design, synthesis, and test of potentially membrane-permeable pyridoxyl-substrate conjugates as inhibitors for human HDC and modeling of an active site for hHDC, which is compatible with the experimental data, overview 4.1.1.28 aromatic-L-amino-acid decarboxylase drug development Parkinson disease, gene therapy, initiation of a phase I safety trial 4.1.1.28 aromatic-L-amino-acid decarboxylase drug development the enzyme is a target for drug development in the therapy of either Parkinson's disease or aromatic amino acid decarboxylase deficiency 4.1.1.32 phosphoenolpyruvate carboxykinase (GTP) drug development potential target for anti-diabetic drugs 4.1.1.33 diphosphomevalonate decarboxylase drug development siRNAs targeting mevalonate (diphospho) decarboxylase (MVD) are found to inhibit Dengue virus replication in a stable A549 subgenomic Renilla replicon cell line (Rluc-replicon) and in naive A549 cells after dengue type 2 (DEN-2) New Guinea C (NGC) live virus infection, knock down of mevalonate (diphospho) decarboxylase can inhibit dengue viral replication 4.1.1.45 aminocarboxymuconate-semialdehyde decarboxylase drug development inhibition of alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase should be explored as a possible novel therapeutic avenue for the treatment of diabetes 4.1.1.48 indole-3-glycerol-phosphate synthase drug development indole-3-glycerol phosphate synthase of Mycobacterium tuberculosis is an attractive target for new anti-Tuberculosis drug development 4.1.2.13 fructose-bisphosphate aldolase drug development Streptococcus pneumoniae fructose-1,6-bisphosphate aldolase is a protein vaccine candidate, elicits Th1/Th2/Th17-type cytokine responses in mice 4.1.2.13 fructose-bisphosphate aldolase drug development the enzyme can be utilized as a broad-spectrum vaccine against various pathogenic bacteria of aquaculture in the future 4.1.2.47 (S)-hydroxynitrile lyase drug development industrial processes 4.1.3.1 isocitrate lyase drug development isocitrate lyase inhibitor design, substitution of a functional group at position C3 in 5-hydroxyindole-type alkaloids by hydrophilic group increases inhibitory activity 4.1.3.1 isocitrate lyase drug development isocitrate lyase inhibitors can be developed for chronic infections but only for use in combination with effective antibiotics 4.1.3.1 isocitrate lyase drug development the enzyme is a target for anti-mycobacterial drug development 4.1.3.36 1,4-dihydroxy-2-naphthoyl-CoA synthase drug development the enzyme is a target for development of antibacterial agents 4.1.3.38 aminodeoxychorismate lyase drug development the absence of the enzyme in humans and its essentiality in various microbes suggests that inhibition of PabC offers the possibility of therapeutics targeting a range of microbial infections, potential of this protein for early stage drug discovery 4.1.99.1 tryptophanase drug development enzyme might serve as a target for antibiotics 4.1.99.12 3,4-dihydroxy-2-butanone-4-phosphate synthase drug development the enzyme is a target in antimicrobial inhibitor development, structure-based inhibitor design 4.1.99.12 3,4-dihydroxy-2-butanone-4-phosphate synthase drug development the enzyme is an attractive target for antibiotics, design of mechanism-based inhibitors 4.1.99.12 3,4-dihydroxy-2-butanone-4-phosphate synthase drug development the enzyme is a potential anti-infective target in the pathogenic yeast 4.2.1.1 carbonic anhydrase drug development Drosophila beta-CA represents a highly active mitochondrial enzyme that is a potential model enzyme for anti-parasitic drug development 4.2.1.1 carbonic anhydrase drug development discovery and development of carbonic anhydrase inhibitors is crucial for their clinical use as antiepileptic, diurectic, and antiglaucoma agents 4.2.1.1 carbonic anhydrase drug development superfamily of metalloenzymes carbonic anhydrases (CAs) has a potential as druggable enzymes to limit the development of Plasmodium falciparum gametocytes 4.2.1.1 carbonic anhydrase drug development the isozymes CA IVX is a possible drug target for the treatment of epilepsy, some retinopathies, and skin tumors 4.2.1.9 dihydroxy-acid dehydratase drug development DHAD can be a potential drug/vaccine target, as it is absent in mammals 4.2.1.10 3-dehydroquinate dehydratase drug development absence of the shikimate patway from humans makes the enzymes of this pathway potential drug targets 4.2.1.10 3-dehydroquinate dehydratase drug development the absence of DHQD in humans and its essentiality in many pathogenic bacteria make the enzyme a target for the development of nontoxic antimicrobials and design of type I DHQD inhibiting molecules 4.2.1.10 3-dehydroquinate dehydratase drug development the enzyme is an attractive target for the development of new antimicrobials and herbicides 4.2.1.11 phosphopyruvate hydratase drug development structure and molecular dynamics applied to design irreversible species-specific inhibitors, parasite-specific lysine residue closely to catalytic site identified 4.2.1.11 phosphopyruvate hydratase drug development the glycolytic/gluconeogenic enzyme enolase is a candidate target for antiparasite drug design 4.2.1.104 cyanase drug development cyanase is potentially an attractive protein target for the development of acaricides 4.2.1.113 o-succinylbenzoate synthase drug development the enzyme plays a major role in menaquinone biosynthesis and is one of the major potential drug targets for development of antibiotics 4.2.1.113 o-succinylbenzoate synthase drug development the enzyme is one of the major potential drug targets for Mycobacterium tuberculosis 4.2.1.114 methanogen homoaconitase drug development the enzyme is a possible antifungal drug target 4.2.1.115 UDP-N-acetylglucosamine 4,6-dehydratase (configuration-inverting) drug development PseB is a potential target for the development of antibiotics 4.2.3.4 3-dehydroquinate synthase drug development potential antibiotic target 4.2.3.4 3-dehydroquinate synthase drug development potential target for new antimicrobial agents, anti-parasitic agents and herbicides 4.2.3.5 chorismate synthase drug development enzymes of shikimate pathway are attractive targets to the development of antitubercular agents 4.2.3.17 taxadiene synthase drug development cancer therapy, taxadiene is the precursor of paclitaxel, a chemotherapeutic agents 4.2.3.17 taxadiene synthase drug development paclitaxel is a successful anticancer drug 4.2.3.20 (R)-limonene synthase drug development D-limonene is effective in cancer prevention in animal cancer models, some clinical applications have been performed 4.2.3.24 amorpha-4,11-diene synthase drug development amorpha-4,11-diene is a precursor of artemisinin, an endoperoxide sesquiterpene lactone produced in plant Artemisia annua L., one of the most important agents in the treatment of malaria, particularly in the form of artemisinin-based combination therapies 4.2.3.24 amorpha-4,11-diene synthase drug development amorpha-4,11-diene is an anti-malarial drug precursor 4.2.99.18 DNA-(apurinic or apyrimidinic site) lyase drug development cancer therapy 4.2.99.18 DNA-(apurinic or apyrimidinic site) lyase drug development APE1 is an attractive therapeutic target in anticancer drug development, there is a link of APE1 overexpression in many cancers to resistance of tumor cells to radio- and chemotherapy. APE1 shows a protective effect in several cancer cell models to a variety of DNA damaging agents. 4.2.99.18 DNA-(apurinic or apyrimidinic site) lyase drug development cancer therapy, human endonuclease III enzyme is a relevant target to potentiate cisplatin cytotoxicity in Y-box binding protein-1 overexpressing tumor cells 4.2.99.18 DNA-(apurinic or apyrimidinic site) lyase drug development inhibition of AP endonuclease may be effective in decreasing the dose requirements of chemotherapeutics used in the treatment of cancer as well as other diseases. 4.2.99.18 DNA-(apurinic or apyrimidinic site) lyase drug development strategies to modulate the proteolytic removal of the APE1 n-terminus will constitute a possible good candidate target for future drug development 4.2.99.21 isochorismate lyase drug development enzyme MbtI represents an appealing target for development of inhibitors of mycobactin biosynthesis since it is structurally and biochemically characterized, has no human orthologues, and is conditionally essential under iron-deficient conditions. Inhibitors are designed against the isochorismatase activity of the enzyme (EC 5.4.4.2) 4.3.1.24 phenylalanine ammonia-lyase drug development AtPAL2 is a very good catalyst for the formation of 3-fluoro-L-phenylalanine, 4-fluoro-L-phenylalanine and 2-chloro-L-phenylalanine. Such noncanonical amino acids are valuable building blocks for the formation of various drug molecules 4.3.1.24 phenylalanine ammonia-lyase drug development the enzyme can reduce the level of L-Phe in the blood and is a prospective drug for the treatment of phenylketonuria 4.3.2.1 argininosuccinate lyase drug development argininosuccinate lyase (ASL) is overexpressed in breast cancer and downregulation of argininosuccinate lyase decreases tumor growth by inhibiting cyclin A2 and NO. Administration of ASL shRNA may be a treatment to prevent cancer cell proliferation and induce cancer cell death 4.3.2.2 adenylosuccinate lyase drug development as Leishmania species lack the de novo pathway and are dependent on the salvage pathway to supply their purine requirements, LbASL could thus represent a drug target for the development of chemical agents to treat leishmaniasis 4.3.2.10 imidazole glycerol-phosphate synthase drug development the enzyme is a potential therapeutic target absent in mammals but present in bacteria, plants, and fungi. Many plant and human pathogens that infect the immunocompromised patient have an IGPS that is highly homologous to the Saccharomyces cerevisiae and Thermotoga maritima enzymes 4.3.3.2 strictosidine synthase drug development cooverexpression of geraniol-10-hydroxylase and strictosidine synthase improves anti-cancer drug camptothecin accumulation in Ophiorrhiza pumila 4.3.3.2 strictosidine synthase drug development for modern industrial drug discovery, construction of alkaloid libraries with complex scaffolds and huge backbone diversity is of paramount importance. Strategies are reported that depend on single step strictosidine synthase-catalyzed reaction. Enzyme reengineering combined with chemical methodologies is straightforward to be accessed to produce a bunch of novel alkaloids with great scaffold diversity 4.3.3.6 pyridoxal 5'-phosphate synthase (glutamine hydrolysing) drug development the enzyme is a target for anti-tuberculosis agents development 4.3.3.7 4-hydroxy-tetrahydrodipicolinate synthase drug development DHDPS is a potential antibiotic target 4.3.3.7 4-hydroxy-tetrahydrodipicolinate synthase drug development the allosteric binding site of DHDPS may be a good starting point for development of an inhibitor specific to Neisseria meningitidis 4.3.3.7 4-hydroxy-tetrahydrodipicolinate synthase drug development the intracellular enzyme dihydrodipicolinate synthase a potential drug target because it is essential for the growth of bacteria while it is absent in humans 4.3.3.7 4-hydroxy-tetrahydrodipicolinate synthase drug development the enzyme is a bona fide drug target for treatment of the Crown Gall disease on crops caused by Agrobacterium tumefaciens, rational design of pesticide agents 4.3.3.7 4-hydroxy-tetrahydrodipicolinate synthase drug development the enzyme is an attractive target for rational antibiotic and herbicide design 4.3.3.7 4-hydroxy-tetrahydrodipicolinate synthase drug development the enzyme is an attractive target for the design and synthesis of herbicides and antibiotics 4.3.3.7 4-hydroxy-tetrahydrodipicolinate synthase drug development the enzyme is a promising antibiotic target 4.3.3.7 4-hydroxy-tetrahydrodipicolinate synthase drug development the enzyme is a target for antibiotics 4.3.3.7 4-hydroxy-tetrahydrodipicolinate synthase drug development the enzyme is an anti-cholera target 4.4.1.4 alliin lyase drug development a monoclonal antibody (MAb) against Aspergillus fumigatus is produced and chemically ligated to the enzyme alliinase. The purified antibody-alliinase conjugate binds to conidia and hyphae of Aspergillus fumigatus at nanomolar concentrations. In the presence of alliin, the conjugate produces cytotoxic allicin molecules, which kills the fungus 4.4.1.4 alliin lyase drug development Pure allicin is prepared by reacting synthetic alliin with a stabilized process of the garlic enzyme alliinase. A novel drug vector, polybutylcyanoacrylate (PBCA) nanoparticles has been developed by emulsion polymerization method and wrapps the pure allicin into it. Minimal inhibitory fungal concentration (MIC) and minimal fungicidal concentration (MFC) of pure allicin and PBCA-allicin NPs against six fungus strains (Candida albicans, Cryputococcus neoformans, Trichophyton rubum, Microsporum gypseum, Microsporum canis and Epidermophyton floccosum) in vitro are used to evaluate their anti-fungal efficacy 4.4.1.5 lactoylglutathione lyase drug development difference of the substrate specificity of the human and the Leishmania enzyme could be used for designing selective inhibitors against the parasite 4.4.1.5 lactoylglutathione lyase drug development beta-ketoesters function as a possible zinc-chelating component of Glx-I inhibitors 4.4.1.5 lactoylglutathione lyase drug development design of a metabolically stable glyoxalase-I inhibitor, which may be useful in potentiating the antitumor activity of alpha-ketoaldehydes 4.4.1.5 lactoylglutathione lyase drug development mutually exclusive substrate specificities and substantial differences between the active sites of the Leishmania major and human GLO1 enzymes indicate that selective inhibition of LmGLO1 may be possible 4.4.1.5 lactoylglutathione lyase drug development cancer therapy, inhibitors of the glyoxalase system would be expected to suppress the growth of cancer cells and could find clinical use as anticancer drug 4.4.1.5 lactoylglutathione lyase drug development the enzyme is a promising drug target, since the functional monomeric Glo1 from Plasmodium falciparum differs significantly from its human homologue 4.4.1.11 methionine gamma-lyase drug development endotoxins cause fever in humans and must be eliminated from biopharmaceuticals intended for parenteral administration which are produced by Escherichia coli. Endotoxins can be drastically removed by anion-exchange column chromatography. Thus, the combination of crystallization and anion-exchange column chromatography is suitable for purification of the enzyme 4.4.1.11 methionine gamma-lyase drug development methyl mercaptan may not only cause oral malodour but also play an important role in the pathogenicity of Treptonema denticola. The enzyme may be an exploitable target for novel chemotherapeutic drugs. An inhibitor of METase may represent a new class of compounds with the potential for preventing and treating oral malodor 4.4.1.20 leukotriene-C4 synthase drug development leukotrienes are an important therapeutic target in asthma and inflammatory diseases 4.4.1.20 leukotriene-C4 synthase drug development although structural differences near the active site and along the C-terminal alpha-helix V suggest that the mouse and human enzymes may function differently in vivo, the mouse enzyme is a useful tool in pharmacological research and drug development 4.6.1.1 adenylate cyclase drug development CyaA substantially contributes to the pathogenesis of whooping cough, catalytic site of CyaA possesses substantial conformational freedom to accommodate structurally diverse ligands, certain ligands bind to CyaA even in the absence of calmodulin, facilitating future inhibitor design 4.6.1.1 adenylate cyclase drug development stable AC2-expressing CHODUKX cell line in which the generation of high expressing GPCR receptor/AC2 lines can retain their functional responsiveness and can provide pharmacological drug comparisons between the same host line for screening purposes and measurement of multiple cellular parameters 4.6.1.1 adenylate cyclase drug development AC1 is a potential drug target site to improve long-term remote memor 4.6.1.2 guanylate cyclase drug development the soluble guanylate cyclase is a target for compounds used in therapy of heart failure, e.g. nitric oxide-independent, soluble guanylate cyclase activator cinaciguat, BAY 58-2667, that induces vasodilation preferentially in diseased vessels, overview 4.6.1.12 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase drug development framework for the development of IspF inhibitors to generate lead compounds of therapeutic potential against microbial pathogens 4.6.1.18 pancreatic ribonuclease drug development the enzyme is an antitumor drug candidate 4.6.1.24 ribonuclease T1 drug development bacterial RNases are promising tools for the development of anticancer drugs. Binase affects the total amount of intracellular RNA and the expression of proapoptotic and antiapoptotic mRNAs 5.1.1.1 alanine racemase drug development the enzyme is an attractive target for antimicrobial drug development 5.1.1.1 alanine racemase drug development Alr is a target for the development of antibacterial drugs 5.1.1.1 alanine racemase drug development the enzyme is a potential target for development of antibiotic compounds 5.1.1.1 alanine racemase drug development the enzyme is a target for antibiotic drug development, especially the dimer interface a potential target for structure-aided drug design 5.1.1.1 alanine racemase drug development the enzyme is an attractive target for designing antibacterial drugs 5.1.1.3 glutamate racemase drug development glutamate racemase is an enzyme essential to the bacterial cell wall biosynthesis pathway, and is therefore considered as a target for antibacterial drug discovery 5.1.1.3 glutamate racemase drug development einzyme is potentially an attractive target for the development of new antibacterial agents because of being an essential enzyme 5.1.1.3 glutamate racemase drug development enzyme is an attractive target for the development of antibacterial agents 5.1.1.3 glutamate racemase drug development glutamate racemase is an attractive target for the design of antibacterial agents 5.1.1.3 glutamate racemase drug development inhibitors of glutamate racemase are potential targets as antibiotic agents against Helicobacter pylori 5.1.1.3 glutamate racemase drug development enzyme MurI is essential and can serve as a target for structure-aided drug design 5.1.1.3 glutamate racemase drug development the enzyme is a good target for antibacterial drug development for treatment of Burkholderia cenocepacia infections causing cystic fibrosis 5.1.1.4 proline racemase drug development enzyme has potential to be used as a drug target for this parasite-based trypanosomiasis 5.1.1.7 diaminopimelate epimerase drug development bacterial racemase, including glutamate racemase and DAP epimerase, are potential targets for the development of new agents effective against organisms resistant to conventional antibiotics 5.1.1.7 diaminopimelate epimerase drug development diaminopimelate epimerase catalyzes the stereoinversion of LL-diaminopimelate to meso-diaminopimelate, a precursor of L-lysine and an essential component of the bacterial peptidoglycan. This function is vital to bacteria and the enzyme therefore represents an attractive target for the design of novel anti-bacterials 5.1.1.7 diaminopimelate epimerase drug development the recombinant DapF produced is correctly folded and is a suitable tool for a drug development study 5.1.1.7 diaminopimelate epimerase drug development DAP epimerase is an attractive target for rational antibiotic design 5.1.1.7 diaminopimelate epimerase drug development enzyme represents a promising target for rational drug design aimed to develop new selective antibacterial therapeutic agents 5.1.1.7 diaminopimelate epimerase drug development the enzme is an attractive target to facilitate development of antibacterial agents 5.1.1.7 diaminopimelate epimerase drug development the enzyme is a promising antimicrobial target 5.1.1.7 diaminopimelate epimerase drug development DapF is considered as an attractive target for the development of antibacterial drugs 5.1.1.18 serine racemase drug development serine racemase inhibitors might be useful in treatment of neurodegenrative diseases 5.1.1.18 serine racemase drug development serine racemase is a promising target for the development of specific inhibitors in the treatment of disorders related to NMDAR dysfunction. Analysis of the molecular basis for rational drug design using the X-ray crystal structures of human and rat serine racemase 5.1.1.18 serine racemase drug development serine racemase inhibitors are therapeutic candidates for the treatment of neurodegenerative disorders and epileptic states 5.1.1.18 serine racemase drug development the enzyme and enzyme mutants may serve as targets for future docking studies and drug design 5.1.3.14 UDP-N-acetylglucosamine 2-epimerase (non-hydrolysing) drug development the enzyme is a target for development of antibiotic agent for treatment of infections caused by Gram-positive bacteria, such as Staphylococcus aureus and Bacillus anthracis 5.1.3.14 UDP-N-acetylglucosamine 2-epimerase (non-hydrolysing) drug development Staphylococcus aureus is a leading cause of hospital and community-acquired infections by Gram-positive bacteria and Staphylococcus epidermidis has emerged as the most common cause of biofilm infections on medical implant devices. Enzyme MnaA serves as a Staphylococcal antibiotic target with cognate inhibitors predicted to possess dual therapeutic benefit: as combination agents to restore beta-lactam efficacy against MRSA and MRSE and as non-bioactive prophylactic agents to prevent Staphylococcal biofilm formation 5.1.99.4 alpha-methylacyl-CoA racemase drug development AMACR can be an attractive target for cytotoxic T-lymphocyte-based immunotherapy for cancer 5.1.99.7 dihydroneopterin triphosphate 2'-epimerase drug development the tetrahydrofolate biosynthetic pathway is an established target for important drugs 5.3.1.9 glucose-6-phosphate isomerase drug development PGI might be a good target for species-specific drug design 5.3.1.9 glucose-6-phosphate isomerase drug development the enzyme is a target for development of specific inhibitors against Echinococcus multilocularismetacestodes and disease alveolar echinococcosis, overview 5.3.1.9 glucose-6-phosphate isomerase drug development the enzyme is a valid drug target against protozoa in coccidiosis 5.3.2.1 phenylpyruvate tautomerase drug development the tautomerase activity of MIF is a target for inhibitor development, overview 5.3.3.12 L-dopachrome isomerase drug development the tautomerase activity of MIF is a target for inhibitor development, overview 5.3.4.1 protein disulfide-isomerase drug development PDI constitutes a potential target for the development of alternative therapy strategies based on the inhibition of folding and chaperoning of exported proteins 5.3.99.3 prostaglandin-E synthase drug development the enzyme constitues an attractive drug target for treatment of inflammatory diseases 5.3.99.3 prostaglandin-E synthase drug development the enzyme is a potential target for therapy of breast cancer 5.3.99.3 prostaglandin-E synthase drug development the enzyme represents a novel target for anti-inflammatory and anti-cancer drugs 5.4.2.2 phosphoglucomutase (alpha-D-glucose-1,6-bisphosphate-dependent) drug development the activity of the PGM gene of Streptococcus iniae is linked to a variety of structural and functional phenotypes that translate to dramatically decreased virulence in a model of fish meningoencephalitis 5.4.2.11 phosphoglycerate mutase (2,3-diphosphoglycerate-dependent) drug development as a key enzyme in glycolysis and energy metabolism, PGAM is a potential target for novel antibiotics 5.4.2.12 phosphoglycerate mutase (2,3-diphosphoglycerate-independent) drug development TbiPGAM is an attractive molecular target for drug development, the apoenzyme conformation described here provides opportunities for its use in structure-based drug design approaches 5.4.3.11 phenylalanine aminomutase (D-beta-phenylalanine forming) drug development phenylalanine ammonia-lyases and 2,3-aminomutases are emerging as important enzymatic systems as potential target for treating diseases such as phenylketonuria and cancer 5.4.4.2 isochorismate synthase drug development enzyme MbtI represents an appealing target for development of inhibitors of mycobactin biosynthesis since it is structurally and biochemically characterized, has no human orthologues, and is conditionally essential under iron-deficient conditions. Inhibitors are designed against the isochorismatase activity of the enzyme (EC 5.4.4.2) 5.4.99.5 chorismate mutase drug development the enzyme serves as a potential target for the development of inhibitors specific to the pathogen 5.4.99.5 chorismate mutase drug development advantage of the nonoccurance of CMs in human, develop antimicrobial drugs to combat dreaded human pathogens such as Mycobacterium tuberculosis 5.4.99.5 chorismate mutase drug development fighting diseases such as tuberculosis. Since vertebrates lack the shikimate pathway for the biosynthesis of aromatic compounds and thus do not possess chorismate mutase activity, this enzyme represents a prime target for the development of antibiotics, fungicides and herbicides 5.4.99.5 chorismate mutase drug development MtCM might play a role in host-pathogen interactions, making it an important target for designing inhibitor molecules against the deadly pathogen 5.4.99.5 chorismate mutase drug development multiple-drug-resistant tuberculoses bacillus and its synergism with HIV-characterization of new enzyme targets and the development of new drugs 5.4.99.5 chorismate mutase drug development Since this enzyme is absent from mammals, it represents a promising target for the development of new antimycobacterial drugs, which are needed to combat Mycobacterium tuberculosis, the causative agent of tuberculosis 5.4.99.5 chorismate mutase drug development since vertebrates lack the shikimate pathway for the biosynthesis of aromatic compounds and thus do not possess chorismate mutase activity, the enzyme represents a prime target for the development of antibacterials 5.4.99.5 chorismate mutase drug development the secretory isozyme is a target for the discovery of anti-tubercular agents 5.4.99.7 Lanosterol synthase drug development results identify a particularly promising new family of OSC inhibitors, for the development of novel antiparasitic agents 5.4.99.7 Lanosterol synthase drug development the enzyme represents a novel target for treatment of hypercholesterolemia and atherosclerosis 5.4.99.7 Lanosterol synthase drug development the enzyme represents a target for the discovery of novel anticholesteraemic drugs 5.4.99.9 UDP-galactopyranose mutase drug development blocking the incorporation of the product galactofuranose into polysaccharides essential for pathogen viability or virulence may lead to novel therapeutics 5.4.99.9 UDP-galactopyranose mutase drug development the product galactofuranose is valued as an important target for the development of new antituberculosis drugs 5.4.99.9 UDP-galactopyranose mutase drug development UGM inhibition may provide an attractive drug target in those eukaryotes where galactofuranose plays a critical role in cellular viability and virulence 5.4.99.9 UDP-galactopyranose mutase drug development inhibitors of the enzyme that block the biosynthesis of UDP-galactofuranose can lead to novel chemotherapeutics for treating Aspergillus fumigatus-related diseases 5.4.99.9 UDP-galactopyranose mutase drug development since the enzyme does not exist in Homo sapiens, the parasite enzyme is a target for drug design 5.4.99.9 UDP-galactopyranose mutase drug development the enzyme is a potential drug target involved in the synthesis of the cell wall of this fungal pathogen 5.4.99.9 UDP-galactopyranose mutase drug development since the enzyme is not present in mammals, it is a promising target for the design of drugs to treat the Chagas' disease caused by Trypanosoma cruzi in humans 5.4.99.9 UDP-galactopyranose mutase drug development the enzyme is a cell surface virulence factor in protozoan parasites and absent in humans, it is therefore a good drug target 5.4.99.9 UDP-galactopyranose mutase drug development UDP-galactopyranose mutase (UGM), a key enzyme in the biosynthesis of mycobacterial cell walls, is a potential target for the treatment of tuberculosis 5.4.99.18 5-(carboxyamino)imidazole ribonucleotide mutase drug development the enzyme in the de novo purine biosynthesis pathway is an attractive target for antibacterial drug design. Zenobia fragment library screening by saturation transfer difference nucleus magnetic resonance (STD-NMR), water-ligand observed via gradient spectroscopy (WaterLOGSY) NMR, and surface plasmon resonance (SPR) methods, method optimization, overview. The selected compouds are categorized into five different basic scaffolds, and at least two fragments from two different scaffolds exhibit inhibitory activity against the BaPurE enzyme 5.6.2.1 DNA topoisomerase drug development 3,3’-diindolylmethane is a novel Leishmania donovani topoisomerase I poison which acts as a noncompetitive inhibitor. So this intriguing dietary component might be exploited for therapeutic development against leishmaniasis 5.6.2.1 DNA topoisomerase drug development anticancer agents that target TOP1 achieve their cytotoxic effects by stabilizing and trapping the cleavable TOP1-DNA complex, which ultimately leads to the accumulation of DNA strand breaks and cell death 5.6.2.1 DNA topoisomerase drug development dimeric compounds are promising candidates to be further elaborated as anticancer leads 5.6.2.1 DNA topoisomerase drug development DNA topoisomerase I is a potential target for chemotherapy 5.6.2.1 DNA topoisomerase drug development DNA topoisomerase I is an important cellular target in drug discovery 5.6.2.1 DNA topoisomerase drug development potential target for drug treatment against smallpox and molluscum contagiosum virus 5.6.2.1 DNA topoisomerase drug development to identify new molecular targets for antiparasitic drugs, attention focuses on DNA topoisomerases 5.6.2.1 DNA topoisomerase drug development Top1 inhibitors approved for the treatment of cancer 5.6.2.1 DNA topoisomerase drug development topoisomerase poisoning has been recognized as an effective approach for the development of chemotherapeutics 5.6.2.1 DNA topoisomerase drug development topoisomerase–drug interactions for clinical development of chemotherapeutics 5.6.2.1 DNA topoisomerase drug development comparison of the target sites in plants exploited for obtaining additional information on drug-target interaction and for designing advanced drugs to prevent resistance in cancer cells and combat drug resistance 5.6.2.1 DNA topoisomerase drug development enzyme is target of several anticancer drugs 5.6.2.1 DNA topoisomerase drug development inhibitors are antitumor agents 5.6.2.1 DNA topoisomerase drug development inhibitors promising lead compounds of novel antitumor drugs 5.6.2.1 DNA topoisomerase drug development topo-I inhibitors as new anticancer drugs 5.6.2.1 DNA topoisomerase drug development the enzyme is an attractive target for discovery of novel tuberculosis drugs that act by enhancing the accumulation of the topoisomerase-DNA cleavage product 5.6.2.1 DNA topoisomerase drug development the enzyme is a potential selective target for chemotherapy and drug development against malaria 5.6.2.1 DNA topoisomerase drug development the enzyme is often upregulated in cancer cells, and it is a target for chemotherapeutic drugs of the camptothecin family 5.6.2.2 DNA topoisomerase (ATP-hydrolysing) drug development enzyme is target of several useful anticancer drugs 5.6.2.2 DNA topoisomerase (ATP-hydrolysing) drug development class of anthracyclines seems to be a good source for selection of anticancer drugs directed toward cancer cells with the developed multidrug resistance attributed to the presence of altered DNA topoisomerase II 5.6.2.2 DNA topoisomerase (ATP-hydrolysing) drug development type IIalpha DNA topoisomerase is among the most important clinical drug targets for the treatment of cancer 6.1.1.1 tyrosine-tRNA ligase drug development the enzyme is a promising target for development of novel selective inhibitors as putative antituberculosis drugs 6.1.1.1 tyrosine-tRNA ligase drug development the LdTyrRS and its extra pocket structure can be a target for development of selective tyrosyl-tRNA synthetase inhibitors and drug design to treat leishmaniosis 6.1.1.1 tyrosine-tRNA ligase drug development TyrRS enzymes are candidates for therapeutic targets in the prevention and therapy of microbial infections 6.1.1.3 threonine-tRNA ligase drug development targeting threonyl-tRNA synthetase (ThrRS) of Brucella abortus is a promising approach to developing small-molecule drugs against bovine brucellosis 6.1.1.4 leucine-tRNA ligase drug development LeuRS is a potential target for antiparasitic drug development 6.1.1.4 leucine-tRNA ligase drug development leucyl-tRNA synthetase (LeuRS) is an attractive therapeutic target and a target for development of drugs 6.1.1.5 isoleucine-tRNA ligase drug development isoleucine utilization is an essential pathway that can be targeted for antimalarial drug development 6.1.1.6 lysine-tRNA ligase drug development aminoacyl-tRNA synthetases are attractive targets for the discovery of antibacterial agents 6.1.1.6 lysine-tRNA ligase drug development LysU is also useful as a tool for highly controlled phosphate-phosphate bond formation between nucleotides, avoiding the need for complex protecting group chemistries. Resulting high yielding tandem LysU-based biosynthetic-synthetic/synthetic-biosynthetic strategies emerge for the preparation of varieties of ApnA analogues directly from inexpensive natural nucleotides and nucleosides. Analogues so formed make a useful small library with which to probe ApnA activities in vitro and in vivo leading to the discovery of potentially potent biopharmaceuticals active against chronic pain and other chronic, high-burden disease states 6.1.1.10 methionine-tRNA ligase drug development parasite MetRS is an attractive drug target due to its essential role in protein synthesis and cell survival. Comparative sequence analysis discloses differences between the trypanosome and mammalian methionyl-tRNA synthetases 6.1.1.15 proline-tRNA ligase drug development aminoacyl-tRNA synthetases are attractive targets for the discovery of antibacterial agents 6.1.1.16 cysteine-tRNA ligase drug development aminoacyl-tRNA synthetases are attractive targets for the discovery of antibacterial agents 6.1.1.17 glutamate-tRNA ligase drug development design of better inhibitors specific for bacterial GluRSs, which are promising targets for antimicrobial therapy 6.1.1.17 glutamate-tRNA ligase drug development inhibitor glutamyl-sulfamoyl-adenosine, Glu-AMS, derivatives with bactericidal properties and low toxicity for humans can be developed 6.1.1.18 glutamine-tRNA ligase drug development the essential nature of the enzymes makes it an attractive targets for designing of drugs against important pathogenic protozoans like Toxoplasma 6.1.1.22 asparagine-tRNA ligase drug development Brugia malayi asparaginyl-tRNA synthetase, a target for anti-parasitic drug design 6.1.1.24 glutamate-tRNAGln ligase drug development the apicoplast indirect aminoacylation pathway is a potential drug target 6.2.1.12 4-coumarate-CoA ligase drug development the enzyme is a target for developing effective plant growth inhibitors, overview 6.2.1.26 O-succinylbenzoate-CoA ligase drug development the enzyme is a potential target for the discovery of antibiotics 6.2.1.26 O-succinylbenzoate-CoA ligase drug development the enzyme is an attractive target for blocking menaquinone biosynthesis as an antibacterial strategy 6.2.1.26 O-succinylbenzoate-CoA ligase drug development o-succinylbenzoyl-CoA synthetase, or MenE, is an essential adenylate-forming enzyme targeted for development of antibiotics in the menaquinone biosynthesis 6.2.1.32 anthranilate-CoA ligase drug development the enzyme might be an attractive target for anti-infective agents 6.2.1.45 E1 ubiquitin-activating enzyme drug development the ubiquitin-activating enzyme E1 is a therapeutic target for the treatment of restenosis 6.3.1.2 glutamine synthetase drug development the enzyme is a potential antimycobacterial drug target 6.3.1.2 glutamine synthetase drug development the enzyme is a target for design of structure-based specific inhibitors 6.3.1.2 glutamine synthetase drug development the enzyme is an attractive target for development of antimycobacterial drugs 6.3.1.2 glutamine synthetase drug development the GSI-alpha-specific regulatory network can be exploited for inhibitor design against Gram-positive pathogens 6.3.1.2 glutamine synthetase drug development GlnA1 may not be a suitable target to find anti-tubercular drugs 6.3.1.2 glutamine synthetase drug development glutamine synthetase is a potential drug target in Mycobacterium tuberculosis 6.3.1.2 glutamine synthetase drug development inhibition of glutamine synthetase is one of the most promising strategies for the discovery of drugs against tuberculosis. The bone-targeting properties of the bisphosphonate compounds make them attractive agents for the treatment of bone tuberculosis 6.3.1.5 NAD+ synthase drug development enzymes involved in NAD metabolism and synthesis are significant drug targets as NAD is a central player in several cellular processes 6.3.1.5 NAD+ synthase drug development NadE is a antimycobacterial drug target 6.3.1.8 glutathionylspermidine synthase drug development the enzyme is a target for drug development 6.3.1.9 trypanothione synthase drug development the enzyme is a target for drug development 6.3.1.9 trypanothione synthase drug development the enzyme is a target for drug development for treatment of human African trypanosomiasis caused by Trypanosoma brucei gambiense and rhodesiense 6.3.1.9 trypanothione synthase drug development trypanothione synthetase is a validated drug target 6.3.1.12 D-aspartate ligase drug development D-aspartate ligase of Enterococcus faecium is an attractive target for the development of narrow-spectrum antibacterial agents that are active against multidrug-resistant Enterococcus faecium 6.3.1.13 L-cysteine:1D-myo-inositol 2-amino-2-deoxy-alpha-D-glucopyranoside ligase drug development MshC may represent a novel target for new classes of antituberculars 6.3.1.13 L-cysteine:1D-myo-inositol 2-amino-2-deoxy-alpha-D-glucopyranoside ligase drug development the enzyme is a potential target for drugs directed against tuberculosis 6.3.1.13 L-cysteine:1D-myo-inositol 2-amino-2-deoxy-alpha-D-glucopyranoside ligase drug development mycothiol cysteine ligase (MshC) is a promising target for developing anti-mycobacterial compounds 6.3.1.19 prokaryotic ubiquitin-like protein ligase drug development the enzyme is a target for drug development in tuberculosis treatment 6.3.1.20 lipoate-protein ligase drug development LplA1, but not LplA2, required for intracellular replication and/or virulence of Listeria monocytogenes 6.3.2.1 pantoate-beta-alanine ligase (AMP-forming) drug development Mycobacterium tuberculosis pantothenate synthetase (MTBPS) is a target for drug design in treatment of tuberculosis 6.3.2.1 pantoate-beta-alanine ligase (AMP-forming) drug development the enzyme is an appropriate target for development of therapeutics to treat tuberculosis 6.3.2.2 glutamate-cysteine ligase drug development the enzyme is a target for development of specific enzyme inhibitors in the treatment of ancylostomiasis 6.3.2.4 D-Alanine-D-alanine ligase drug development the enzyme is a target for antibiotic inhibitor development, overview 6.3.2.4 D-Alanine-D-alanine ligase drug development the enzyme is an attractive and viable target in the search for effective antimicrobial drugs 6.3.2.4 D-Alanine-D-alanine ligase drug development the enzyme is an attractive target for development of antimicrobial drugs 6.3.2.4 D-Alanine-D-alanine ligase drug development DDL is an important drug target for the development of antibacterial agents 6.3.2.4 D-Alanine-D-alanine ligase drug development the enzyme is a target for drug development to combat against Mycobacterium tuberculosis (Mtb) 6.3.2.4 D-Alanine-D-alanine ligase drug development the enzyme is a target for drug development. Acinetobacter baumannii is emerging as a multidrug-resistant nosocomial pathogen, that causes a number of diseases, including pneumonia, bacteremia, meningitis, and skin infections 6.3.2.6 phosphoribosylaminoimidazolesuccinocarboxamide synthase drug development 4-(N-succino)-5-aminoimidazole-4-carboxamide ribonucleotide synthetase (PurC) is an ideal target for the discovery of antimicrobials against the pathogen 6.3.2.8 UDP-N-acetylmuramate-L-alanine ligase drug development the enzymes involved in synthesizing the bacterial cell wall are attractive targets for the design of antibacterial compounds, since this pathway is essential for bacteria and is absent in animals, particularly humans 6.3.2.9 UDP-N-acetylmuramoyl-L-alanine-D-glutamate ligase drug development MurD is a target for small molecule chemotherapeutics 6.3.2.9 UDP-N-acetylmuramoyl-L-alanine-D-glutamate ligase drug development the enzyme is a target in the development of potential antibiotics designed to target the peptidoglycan biosynthetic pathway 6.3.2.10 UDP-N-acetylmuramoyl-tripeptide-D-alanyl-D-alanine ligase drug development AbMurF is a target for the structure-based development of inhibitors to treat Acinetobacter baumannii infections 6.3.2.12 dihydrofolate synthase drug development enzyme dihydrofolate synthase is a target for development of specific drugs against infections with the human pathogen Pneumocystis jirovecii that can cause pneumonia 6.3.4.2 CTP synthase (glutamine hydrolysing) drug development daily injection of acivicin in trypanosome-infected mice suppresses the infection up to one month without any significant loss of weight. Experiments with cultured bloodstream Trypanosoma brucei shows that acivicin is trypanocidal if present at 0.001 nM concentration for at least 4 d. Acivicin may qualify as a drug with desirable properties, i.e. cure within 7 d, according to the current Target Product Profiles of WHO and DNDi 6.3.4.2 CTP synthase (glutamine hydrolysing) drug development modifying 2-aminopurine or 2-aminopurine riboside may serve as an effective strategy for developing CTPS inhibitors 6.3.4.2 CTP synthase (glutamine hydrolysing) drug development structure serves as a basis for structure-based design of anti-proliferative inhibitors 6.3.4.2 CTP synthase (glutamine hydrolysing) drug development CTP is a recognized target for the development of anticancer, antiviral, and antiprotozoal agents 6.3.4.3 formate-tetrahydrofolate ligase drug development MTHFD1L overexpression is closely associated with aggressive clinicopathological features of hepatocellular carcinoma (HCC) including the presence of tumor microsatellite formation, venous invasion, and more advanced tumor stages. The enzyme MTHFD1L is a potential target in cancer therapy. Inhibition of the folate cycle sensitizes HCC cells to sorafenib treatment in vitro and in vivo 6.3.4.5 argininosuccinate synthase drug development high levels of AS expression, which may be required for several arginine-dependent processes in cancer, including the production of nitric oxide, proline, pyrimidines and polyamines, is regulated by TNF-alpha and may provide an important molecular pathway linking inflammation and metabolism to ovarian tumorigenesis 6.3.4.15 biotin-[biotin carboxyl-carrier protein] ligase drug development the enzyme is a potential target for anti-mycobacterial drugs 6.3.4.15 biotin-[biotin carboxyl-carrier protein] ligase drug development the enzyme is a target for the design of effective antifungal drugs 6.3.4.15 biotin-[biotin carboxyl-carrier protein] ligase drug development the enzyme is a target for the design of effective antitubercular drugs 6.3.5.4 asparagine synthase (glutamine-hydrolysing) drug development enzyme AS-A is unlikely to be a suitable drug target against Leishmania parasites 6.3.5.4 asparagine synthase (glutamine-hydrolysing) drug development the absence of an LdASNA homologue from humans and its essentiality for the parasites make LdASNA a drug target 6.3.5.5 carbamoyl-phosphate synthase (glutamine-hydrolysing) drug development CPSII is a potential parasite-selective target for drug development 6.4.1.2 acetyl-CoA carboxylase drug development the enzyme is a target for drug development in case of obesity, diabetes, and other symptoms of the metabolic syndrome 6.4.1.2 acetyl-CoA carboxylase drug development the structure of the enzyme's active site can be used for drug discovery 6.4.1.2 acetyl-CoA carboxylase drug development inhibition of ACC demonstrates promising therapeutic potential for treating obesity and type 2 diabetes mellitus in transgenic mice and preclinical animal models 6.4.1.2 acetyl-CoA carboxylase drug development the enzyme is a target for drug development in treatment of obesity 7.1.1.2 NADH:ubiquinone reductase (H+-translocating) drug development carvedilol exerts its protective antioxidant action both by a direct antioxidant effect and by a preconditioning-like mechanism, via inhibition of mitochondrial complex I 7.1.1.2 NADH:ubiquinone reductase (H+-translocating) drug development nucleoside analog reverse transcriptase inhibitors are capable of affecting complex I activity in a non-polymerase-gamma/mtDNA mediated pathway. Elevations in superoxide produced at complex I caused by nucleoside analog reverse transcriptase inhibitors can provide a mechanism for the oxidative stress observed with these drugs 7.1.1.9 cytochrome-c oxidase drug development possibility of nonspecific peroxidation of various substances catalyzed by cytochrome oxidase via the peroxidase mechanism, which may contribute to intracellular metabolism of biologically active drugs (under conditions of cardiotoxicity) and other compounds 7.1.1.9 cytochrome-c oxidase drug development tumor necrosis factor alpha-mediated CcO inhibition leads to tissue dysoxia, which suppresses aerobic ATP production and causes a shift to the glycolytic pathway. Kinases and phosphatases involved in reversible tumor necrosis factor alpha-mediated CcO phosphorylation may be promising targets for drug development because they act on an end point of cell signaling 7.1.2.1 P-type H+-exporting transporter drug development the enzyme is a target for development of specific inhibitors 7.1.2.2 H+-transporting two-sector ATPase drug development the enzyme is a target for development of specific inhibitors 7.1.3.1 H+-exporting diphosphatase drug development VSP1 enzyme an attractive drug target against trypanosomatid parasites 7.2.2.9 P-type Cu2+ transporter drug development ATP7A shown to confer resistance to various anticancer agents on cancer cells, discussed as a good index of drug resistance in clinical colon cancers 7.2.2.9 P-type Cu2+ transporter drug development review on transport mechanisms of platinum-based antitumor agents 7.4.2.8 protein-secreting ATPase drug development the enzyme is a chemotherapeutic target for small-molecule ATPase inhibitors 7.6.2.2 ABC-type xenobiotic transporter drug development MRP4 is a potential target for drug development, e.g. in the treatment of hyperuricaemia