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Information on EC 1.1.1.205 - IMP dehydrogenase and Organism(s) Homo sapiens and UniProt Accession P20839
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1.1.1.205 IMP dehydrogenaseIUBMB Comments
The enzyme acts on the hydroxy group of the hydrated derivative of the substrate.
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Word Map
- 1.1.1.205
-
mycophenolic
- purine
- guanine
- mofetil
- ribavirin
- leukemia
- tiazofurin
-
rejection
- xmp
-
pharmacodynamic
-
salvage
- hypoxanthine
-
cyclosporine
-
allograft
-
prodrugs
- mizoribine
- phosphoribosyltransferase
- ribonucleotide
- xanthosine
-
guanylate
- tad
- calcineurin
- dgtp
- adenylosuccinate
- 6-mercaptopurine
- dihydrofolate
-
hypoxanthine-guanine
- cryptosporidium
- tacrolimus
- thiopurine
- riboside
- azathioprine
- glucuronide
- parvum
- benzamide
- pigmentosa
- sirolimus
- 6-thioguanine
- analysis
- rbv
-
amido
- cryptosporidiosis
-
c-nucleoside
- tritrichomonas
-
enteric-coated
-
predose
- hgprt
- pharmacology
- diagnostics
- drug development
- medicine
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
impdh, imp dehydrogenase, inosine monophosphate dehydrogenase, impdh2, impdh1, inosine 5'-monophosphate dehydrogenase, inosine-5'-monophosphate dehydrogenase, impdh ii, imp dh, inosinate dehydrogenase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
IMPDH1
dehydrogenase, inosinate
-
-
-
-
IMP dehydrogenase
IMP oxidoreductase
-
-
-
-
IMPD
-
-
-
-
IMPDH
IMPDH II
IMPDH2
inosinate dehydrogenase
-
-
-
-
inosine 5'-monophosphate dehydrogenase
inosine 5-monophosphate dehydrogenase
inosine monophosphate dehydrogenase
inosine monophosphate oxidoreductase
-
-
-
-
inosine-5'-phosphate dehydrogenase
-
-
-
-
inosinic acid dehydrogenase
-
-
-
-
Raspberry protein
-
-
-
-
SOI12
-
-
-
-
Superoxide-inducible protein 12
-
-
-
-
IMP dehydrogenase
-
-
-
-
IMPDH
-
-
-
-
IMPDH
-
-
IMPDH2
-
inosine 5'-monophosphate dehydrogenase
-
-
-
-
inosine monophosphate dehydrogenase
-
-
-
-
inosine monophosphate dehydrogenase
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
IMP + NAD+ + H2O = XMP + NADH + H+
reaction and kinetic mechanism, an Arg residue is involved in catalysis as general base
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
redox reaction
-
-
-
-
oxidation
-
-
-
-
reduction
-
-
-
-
PATHWAY SOURCE
PATHWAYS
BRENDA
-
-, -, -
SYSTEMATIC NAME
IUBMB Comments
IMP:NAD+ oxidoreductase
The enzyme acts on the hydroxy group of the hydrated derivative of the substrate.
CAS REGISTRY NUMBER
COMMENTARY
9028-93-7
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
inosine 5'-phosphate + NAD+
xanthosine 5'-phosphate + NADH + H+
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH + H+
-
-
-
?
inosine 5'-phosphate + acetylpyridine adenine dinucleotide + H2O
xanthosine 5'-phosphate + reduced acetylpyridine adenine dinucleotide
-
-
-
-
?
inosine 5'-phosphate + NAD+
xanthosine 5'-phosphate + NADH + H+
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
the enzyme performs the rate-limiting step in guanine nucleotide biosynthesis
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
-
-
347905, 347912, 347918, 347931, 667473, 667935, 667965, 667976, 667980, 670881, 684706, 689355, 706815, 706817
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
-
-
-
-
ir
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
-
rate-limiting step of the de novo guanine nucleotide biosynthesis
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
-
rate-limiting step of the de novo guanine nucleotide biosynthesis
-
-
ir
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH + H+
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH + H+
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH + H+
-
IMPDH catalyzes a dehydrogenase reaction and a hydrolysis reaction, a redox step producing NADH and the covalent intermediate E-xanthosine 5'-monophosphate* and a hydrolysis step that produces xanthosine 5'-monophosphate. The enzyme toggles between the open conformation required for the dehydrogenase reaction and the closed conformation of the hydrolase reaction by moving a mobile flap into the NAD site. The dehydrogenase and hydrolase reactions display significant differences in the host (Homo sapiens) and parasite (Cryptosporidium parvum) enzymes, in keeping with the phylogenetic and structural divergence of their active sites
-
-
?
additional information
?
-
enzyme mutations are involved in autosomal dominant retinitis pigmentosa, pathological mechanism, overview
-
-
?
additional information
?
-
ssDNA and RNA binding of wild-type and mutant IMPDH1s
-
-
?
additional information
?
-
assay method optimization. XMP detection and quantification by anion exchange chromatography
-
-
?
additional information
?
-
assay method optimization. XMP detection and quantification by anion exchange chromatography
-
-
?
additional information
?
-
-
assay method optimization. XMP detection and quantification by anion exchange chromatography
-
-
?
additional information
?
-
-
enzyme inhibition by mycophenolic acid impairs maturation and function of dendritic cells due to low GTP levels and reduced expression of CD80, CD40, CD86, CD54, and CD83 in dendritic cells, accompanied by a decreased capacity to stimulate T-lymphocytes
-
-
?
additional information
?
-
-
increased activities of IMP DH and GMP synthase and in the elevated concentrations of guanylates in hepatomas and other tumor cells
-
-
?
additional information
?
-
-
inhibition of the enzyme in K562 cells sensitizes the before resistant cells to methotrexate
-
-
?
additional information
?
-
-
isozyme IMPDH-1 is essential for T lymphocyte development, enzyme inhibitor mycophenolic acid inhibits tumor-associated angiogenesis
-
-
?
additional information
?
-
-
the enzyme is rate-limiting in the de novo synthesis of guanine nucleotides
-
-
?
additional information
?
-
-
the enzyme binds both RNA and DNA in vitro and in vivo
-
-
?
additional information
?
-
-
the enzyme interacts with GTP which leads to formation of linear arrays, GTP reverses the enzyme aggregation by inhibitor mycophenolic acid
-
-
?
additional information
?
-
assay method optimization. XMP detection and quantification by anion exchange chromatography
-
-
?
additional information
?
-
assay method optimization. XMP detection and quantification by anion exchange chromatography
-
-
?
additional information
?
-
-
assay method optimization. XMP detection and quantification by anion exchange chromatography
-
-
?
additional information
?
-
the enzyme does not hydrolyze oxanosine monophosphate
-
-
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
the enzyme performs the rate-limiting step in guanine nucleotide biosynthesis
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
-
rate-limiting step of the de novo guanine nucleotide biosynthesis
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
-
rate-limiting step of the de novo guanine nucleotide biosynthesis
-
-
ir
additional information
?
-
enzyme mutations are involved in autosomal dominant retinitis pigmentosa, pathological mechanism, overview
-
-
?
additional information
?
-
-
enzyme inhibition by mycophenolic acid impairs maturation and function of dendritic cells due to low GTP levels and reduced expression of CD80, CD40, CD86, CD54, and CD83 in dendritic cells, accompanied by a decreased capacity to stimulate T-lymphocytes
-
-
?
additional information
?
-
-
increased activities of IMP DH and GMP synthase and in the elevated concentrations of guanylates in hepatomas and other tumor cells
-
-
?
additional information
?
-
-
inhibition of the enzyme in K562 cells sensitizes the before resistant cells to methotrexate
-
-
?
additional information
?
-
-
isozyme IMPDH-1 is essential for T lymphocyte development, enzyme inhibitor mycophenolic acid inhibits tumor-associated angiogenesis
-
-
?
additional information
?
-
-
the enzyme is rate-limiting in the de novo synthesis of guanine nucleotides
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
NAD+
comparison between the NAD+ binding sites of human IMPDHs and Mycobacterium tuberculosis IMPDH
NAD+
-
-
347905, 347912, 347916, 347918, 347931, 667473, 667921, 667935, 667937, 667965, 667980, 668351, 670881, 701583, 702243, 703271, 706815, 706817, 761825
NAD+
comparison between the NAD+ binding sites of human IMPDHs and Mycobacterium tuberculosis IMPDH
additional information
involvement of three conserved water molecules (W(L), W(M), and W(C)) in the recognition of catalytic residues (R 322, D 364, and N 303) to cofactor
-
additional information
-
involvement of three conserved water molecules (W(L), W(M), and W(C)) in the recognition of catalytic residues (R 322, D 364, and N 303) to cofactor
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
K+
Na+
NH4+
Rb+
Tl+
additional information
K+
-
enhances inosine 5'-phosphate bound at a stoichiometry of four sites per tetramer and the affinity of the type 2 isozyme by 2fold
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(1R,2R,3R,5S)-2,3,5-trihydroxy-5-(propylcarbamoyl)cyclohexyl (4E)-6-[4-(acetyloxy)-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl]-4-methylhex-4-enoate
-
(2E)-3-furan-2-yl-N-[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]prop-2-enamide
-
(2E)-4-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-2-methylbut-2-enal
-
(2E)-4-[4-(acetyloxy)-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl]-2-methylbut-2-enoic acid
-
(2E)-4-{6-methoxy-7-methyl-3-oxo-4-[2-(trimethylsilyl)ethoxy]-1,3-dihydro-2-benzofuran-5-yl}-2-methylbut-2-enal
-
(2E)-N-(1-oxo-1,3-dihydro-2-benzofuran-5-yl)-3-phenylprop-2-enamide
-
(2E)-N-hydroxy-3-[3-({[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]carbamoyl}amino)phenyl]prop-2-enamide
-
(2E)-N-hydroxy-3-[4-({[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]carbamoyl}amino)phenyl]prop-2-enamide
-
(3aR,4R,6S,7aR)-6-hydroxy-2,2-dimethyl-6-(propylcarbamoyl)hexahydro-2H-1,3-benzodioxol-4-yl (4E)-6-[4-(acetyloxy)-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl]-4-methylhex-4-enoate
-
(3aR,4R,7S,8aR)-7-hydroxy-2,2-dimethyltetrahydro-2H-4,7-methano[1,3]dioxolo[4,5-c]oxepin-6(4H)-one
-
(3aR,5R,7R,7aS)-5,7-dihydroxy-2,2-dimethyl-N-propylhexahydro-2H-1,3-benzodioxole-5-carboxamide
-
(3S)-oxolan-3-yl {[3-({[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]carbamoyl}amino)phenyl]methyl}carbamate
-
(3S,4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-3,4-dimethylhex-4-enoic acid
-
(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)acetaldehyde
-
(4E)-6-(4,6-dihydroxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enoic acid
derivative of mycophenolic acid. IC50 value for K562 cells proliferation 8.2 microM
(4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methyl-N-(1H-1,2,4-triazol-5-yl)hex-4-enamide
-
(4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methyl-N-{[(1-nitro-4a,9a-dihydroacridin-9-yl)amino]methyl}hex-4-enamide
-
(4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methyl-N-{[(4-nitro-9-oxo-4a,9,9a,10-tetrahydroacridin-1-yl)amino]methyl}hex-4-enamide
-
(4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enal
-
(4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
-
(4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enoic acid
-
(4E)-6-[4-(acetyloxy)-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl]-4-methylhex-4-enoic acid
derivative of mycophenolic acid. IC50 value for K562 cells proliferation 0.59 microM
(4E)-N-hydroxy-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
(E)-N-[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]-1-(thiophen-2-yl)methanimine
-
({hydroxy[2-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)ethoxy]phosphoryl}methyl)phosphonic acid
-
1-methyl-6-[(5-phenyl-1,3-oxazol-2-yl)amino]-1H-indole-3-carbonitrile
-
1-[3,4-bis(benzyloxy)-5-oxo-2,5-dihydrofuran-2-yl]ethane-1,2-diyl diacetate
-
1-{5-O-[hydroxy({hydroxy[2-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)ethoxy]phosphoryl}methyl)phosphoryl]-beta-D-ribofuranosyl}-1H-benzimidazol-4-amine
-
14,16-dihydroxy-3,8-dimethyl-3,4,5,6,9,10-hexahydro-1H-2-benzoxacyclotetradecine-1,7(8H)-dione
inhibition of leukemia K562 cells proliferation, IC50 of 71.3 microM
2,2,2-trichloroethyl (1-oxo-1,3-dihydro-2-benzofuran-5-yl)carbamate
-
2-(1-benzothiophen-3-yl)-6-methoxy-5-(1,3-oxazol-5-yl)-1H-indole-3-carbaldehyde
-
2-(methyl{2-[(2lambda~5~-triaza-1,2-dien-2-yl)acetyl]phenyl}amino)-2-oxoethyl acetate
-
2-ethyl-5'-O-[hydroxy({hydroxy[2-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)ethoxy]phosphoryl}methyl)phosphoryl]adenosine
-
2-ethyl-9-[5-O-[hydroxy(2-[hydroxy[2-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)ethoxy]phosphoryl]ethyl)phosphoryl]-beta-L-ribofuranosyl]-9H-purin-6-amine
inhibition of leukemia K562 cells proliferation, IC50 of 4.0 microM
2-[(2-{2-[3-methoxy-4-(1,3-oxazol-5-yl)anilino]-1,3-oxazol-5-yl}phenyl)(methyl)amino]-2-oxoethyl acetate
-
2-[methyl[2-(2-[[3-(1,3-oxazol-5-yl)-1H-indol-6-yl]amino]-1,3-oxazol-5-yl)phenyl]amino]-2-oxoethyl acetate
-
4-[[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]amino]-6-phenyl-1,3,5-triazin-2-ol
-
5'-deoxy-5'-[(3-{[(4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enoyl]amino}-2-oxopropyl)amino]adenosine
-
5'-O-({[2-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]sulfamoyl}methanesulfonyl)adenosine
-
5'-O-[hydroxy({hydroxy[2-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)ethoxy]phosphoryl}methyl)phosphoryl]adenosine
-
6-((E)-4-(((1-(50-deoxy-adenosin-50-yl)-1H-1,2,3-triazol-4-yl)-methyl)amino)-3-methylbut-2-en-1-yl)-7-hydroxy-5-methoxy-4-methylisobenzofuran-1(3H)-one
-
6-((E)-4-(4-(adenosin-50-yl)methyl-1H-1,2,3-triazol-1-yl)-3-methylbut-2-en-1-yl)-7-hydroxy-5-methoxy-4-methylisobenzofuran-1(3H)-one
-
6-{(2E)-4-[4-({[(2S,5R)-5-(6-amino-7,8-dihydro-9H-purin-9-yl)oxolan-2-yl]methoxy}methyl)-1H-1,2,3-triazol-1-yl]-3-methylbut-2-en-1-yl}-7-hydroxy-5-methoxy-4-methyl-2-benzofuran-1(3H)-one
-
7-hydroxy-5-methoxy-4-methyl-6-[(2E)-3-methyl-4-(2lambda~5~-triaza-1,2-dien-2-yl)but-2-en-1-yl]-2-benzofuran-1(3H)-one
-
7-hydroxy-5-methoxy-4-methyl-6-{(2E)-3-methyl-6-[(2R)-oxiran-2-yl]-6-oxohex-2-en-1-yl}-2-benzofuran-1(3H)-one
-
7-hydroxy-5-methoxy-4-methyl-6-{(2E)-3-methyl-6-[(2S)-oxiran-2-yl]-6-oxohex-2-en-1-yl}-2-benzofuran-1(3H)-one
-
7-hydroxy-6-[(2E)-6-hydroxy-3-methylocta-2,7-dien-1-yl]-5-methoxy-4-methyl-2-benzofuran-1(3H)-one
-
7-methoxy-2-(3-methylphenyl)-6-(1,3-oxazol-5-yl)quinolin-4(1H)-one
-
7-methoxy-6-(1,3-oxazol-5-yl)-3-(2-pyridin-4-ylethyl)-2-thioxo-2,3-dihydroquinazolin-4(1H)-one
-
9-(5-O-[hydroxy[([hydroxy[2-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)ethoxy]phosphoryl]oxy)methyl]phosphoryl]-beta-L-ribofuranosyl)-9H-purin-6-amine
homology modeling
AVN944
induces caspase-independent apoptosis in multiple myeloma cell lines and displays antiproliferative activity against both androgen-dependent and androgen-independent prostate cancer cell lines
dimethyl 1-{(2Z)-2-[3,4-bis(benzyloxy)-5-oxofuran-2(5H)-ylidene]ethyl}-4,5-dihydro-1H-imidazole-4,5-dicarboxylate
-
ethyl (2E)-3-[3-methoxy-4-(1,3-oxazol-5-yl)anilino]-3-phenylprop-2-enoate
-
ethyl (2E)-3-[4-({[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]carbamoyl}amino)phenyl]prop-2-enoate
-
ethyl (4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enoyl carbonate
-
imidazo[4,5-e][1,4]diazapine
fat base nucleotide, inosine 5'-phosphate but not NAD+ protects against inhibition
methyl (4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enoate
derivative of mycophenolic acid. IC50 value for K562 cells proliferation 0.73 microM
methyl N-[(4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enoyl]alaninate
-
mycophenolic 2-ethyladenosin-5'-yl-difluoromethylenebis(phosphonate)
potent, sub-micromolar inhibitor of leukemia K562 cells proliferation, IC50 of 0.45 microM
mycophenolic 2-ethyladenosin-5'-yl-methylenebis(phosphonate)
inhibition of leukemia K562 cells proliferation, IC50 of 1.0 microM
N-(2-{2-[3-methoxy-4-(1,3-oxazol-5-yl)anilino]-1,3-oxazol-5-yl}phenyl)-N-methyl-2-(morpholin-4-yl)acetamide
-
N-[(4-fluorophenyl)(1-methyl-1H-imidazol-2-yl)methyl]-2-methyl-3-(1,2,4-thiadiazol-5-yl)-1H-indole-6-carboxamide
-
N-[(4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enoyl]alanine
-
N-[1-[6-(4-ethylpiperazin-1-yl)pyridin-3-yl]-1-methylethyl]-2-fluoro-9-oxo-9,10-dihydroacridine-3-carboxamide
-
N-[2-(2-[[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]amino]-1,3-oxazol-5-yl)phenyl]-N-methyl-2-morpholin-4-ylacetamide
-
N-[2-(hydroxymethyl)cyclopentyl]-N'-[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]propanediamide
-
N-{2-[6-(4-ethylpiperazin-1-yl)pyridin-3-yl]propan-2-yl}-2-fluoro-9-oxo-4a,9,9a,10-tetrahydroacridine-3-carboxamide
-
N1-methyl-N~2~-(1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethanediamide
-
N~1~-hydroxy-N~8~-[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]octanediamide
-
oxolan-3-yl {[3-({[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]carbamoyl}amino)phenyl]methyl}carbamate
-
phenyl N'-cyano-N-(3-[cyano[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]carbamimidamido]benzyl)imidocarbamate
-
S-[(4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-en-1-yl] ethanethioate
-
tert-butyl methyl (1S,4S)-7'-methoxy-3'-methyl-6'-(1,3-oxazol-5-yl)-4'-oxo-3',4'-dihydro-1'H-spiro[cyclopentane-1,2'-quinazoline]-3,4-dicarboxylate
-
thiazofurin-5'-yl-2-ethyladenosin-5'-yl-difluromethylene bis(phosphonate)
inhibition of leukemia K562 cells proliferation, IC50 of 4.7 microM
thiazole-4-carboxamide adenine dinucleotide
inhibition of leukemia K562 cells proliferation, IC50 of 3.7 microM
[(2S,5R)-5-(6-amino-7,8-dihydro-9H-purin-9-yl)oxolan-2-yl]methyl cyanate
-
(1R,2R,3R,5S)-2,3,5-trihydroxy-5-(propylcarbamoyl)cyclohexyl (4E)-6-[4-(acetyloxy)-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl]-4-methylhex-4-enoate
-
(2-[acetyl[(2E)-4-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-2-methylbut-2-en-1-yl]amino]ethyl)phosphonic acid
-
isozyme IMPDH II IC50: 785 nM
(2-[formyl[(2E)-4-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-2-methylbut-2-en-1-yl]amino]ethyl)phosphonic acid
-
isozyme IMPDH II IC50: 749 nM
(2-[[(2E)-4-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-2-methylbut-2-en-1-yl](methyl)amino]ethyl)phosphonic acid
-
isozyme IMPDH II IC50: above 0.001 mM
(2-[[(2E)-4-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-2-methylbut-2-en-1-yl](methylsulfonyl)amino]ethyl)phosphonic acid
-
isozyme IMPDH II IC50: 498 nM
(2-[[(2E)-4-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-2-methylbut-2-en-1-yl](sulfamoyl)amino]ethyl)phosphonic acid
-
isozyme IMPDH II IC50: 93 nM
(2-[[(2E)-4-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-2-methylbut-2-en-1-yl]amino]ethyl)phosphonic acid
-
isozyme IMPDH II IC50: 499 nM
(2-[[(2E)-4-(6-ethyl-4-hydroxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-2-methylbut-2-en-1-yl](methyl)amino]ethyl)phosphonic acid
-
isozyme IMPDH II IC50: 132 nM
(2-[[(2E)-4-(6-ethyl-4-hydroxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-2-methylbut-2-en-1-yl](methylsulfonyl)amino]ethyl)phosphonic acid
-
isozyme IMPDH II IC50: 68 nM
(2-[[(2E)-4-(6-ethyl-4-hydroxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-2-methylbut-2-en-1-yl](sulfamoyl)amino]ethyl)phosphonic acid
-
isozyme IMPDH II IC50: 24 nM
(2-[[(2E)-4-(6-ethyl-4-hydroxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-2-methylbut-2-en-1-yl]amino]ethyl)phosphonic acid
-
isozyme IMPDH II IC50: 13 nM
(2E)-3-furan-2-yl-N-[4-(4-methyl-1,3-oxazol-5-yl)phenyl]prop-2-enamide
-
isozyme IMPDH II IC50: 0.002 mM
(2E)-3-{3-[N''-cyano-N'-(4-cyano-3-methoxyphenyl)carbamimidamido]phenyl}prop-2-enoic acid
-
(2E)-4-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-2-methylbut-2-enal
-
(2E)-4-[4-(acetyloxy)-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl]-2-methylbut-2-enoic acid
-
(2E)-4-{6-methoxy-7-methyl-3-oxo-4-[2-(trimethylsilyl)ethoxy]-1,3-dihydro-2-benzofuran-5-yl}-2-methylbut-2-enal
-
(2E)-N-(1-oxo-1,3-dihydro-2-benzofuran-5-yl)-3-phenylprop-2-enamide
-
(2E)-N-(4-chlorophenyl)-4-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)but-2-enamide
-
(2E)-N-hydroxy-3-[3-({[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]carbamoyl}amino)phenyl]prop-2-enamide
-
(2E)-N-hydroxy-3-[4-({[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]carbamoyl}amino)phenyl]prop-2-enamide
-
(2R)-1-cyanobutan-2-yl [(1S)-1-(3-{[(2,3-dihydro-1-benzofuran-7-yl)carbamoyl]amino}phenyl)ethyl]carbamate
-
(2R)-1-cyanobutan-2-yl [(1S)-1-(3-{[(2-acetyl-1-methyl-2,3-dihydro-1H-benzimidazol-4-yl)carbamoyl]amino}phenyl)ethyl]carbamate
-
(2R)-1-cyanobutan-2-yl [(1S)-1-(3-{[(2-methoxyquinoxalin-5-yl)carbamoyl]amino}phenyl)ethyl]carbamate
-
(2R)-1-cyanobutan-2-yl [(1S)-1-(3-{[(2-methyl-4-oxo-3,4-dihydro-2H-1-benzopyran-6-yl)carbamoyl]amino}phenyl)ethyl]carbamate
-
(2R)-1-cyanobutan-2-yl [(1S)-1-(3-{[(2H-1,3-benzodioxol-5-yl)carbamoyl]amino}phenyl)ethyl]carbamate
-
(2R)-1-cyanobutan-2-yl [(1S)-1-(3-{[(3,4-dimethoxybenzene-1-sulfonyl)carbamoyl]amino}phenyl)ethyl]carbamate
-
(2R)-1-cyanobutan-2-yl [(1S)-1-(3-{[(3-methoxy-4-methylphenyl)carbamoyl]amino}phenyl)ethyl]carbamate
-
(2R)-1-cyanobutan-2-yl [(1S)-1-(3-{[(3-methoxyquinoxalin-5-yl)carbamoyl]amino}phenyl)ethyl]carbamate
-
(2R)-1-cyanobutan-2-yl [(1S)-1-(3-{[(4-cyano-3-methoxyphenyl)carbamoyl]amino}phenyl)ethyl]carbamate
i.e. VX-4997
(2R)-1-cyanobutan-2-yl [(1S)-1-(3-{[(4-methyl-2,3-dihydro-1-benzofuran-6-yl)carbamoyl]amino}phenyl)ethyl]carbamate
-
(2R)-1-cyanobutan-2-yl [(1S)-1-(3-{[(4-oxo-3,4-dihydro-2H-1-benzopyran-6-yl)carbamoyl]amino}phenyl)ethyl]carbamate
-
(2R)-1-cyanobutan-2-yl [(1S)-1-(3-{[(5,6-dihydro-1,4-dioxin-2-yl)carbamoyl]amino}phenyl)ethyl]carbamate
-
(2R)-1-cyanobutan-2-yl [(1S)-1-(3-{[(6,7-dimethoxynaphthalen-1-yl)carbamoyl]amino}phenyl)ethyl]carbamate
-
(2R)-1-cyanobutan-2-yl [(1S)-1-(3-{[(E)-1-(3,4-dimethoxyanilino)-2-nitroethenyl]amino}phenyl)ethyl]carbamate
-
(2R)-1-cyanobutan-2-yl [(1S)-1-(3-{[(E)-1-(4-cyano-3-methoxyanilino)-2-nitroethenyl]amino}phenyl)ethyl]carbamate
-
(2R)-1-cyanobutan-2-yl [(1S)-1-(3-{[4-(4-cyano-3-methoxyphenyl)piperazine-1-carbonyl]amino}phenyl)ethyl]carbamate
-
(2R)-1-cyanobutan-2-yl [(1S)-1-(3-{[5-(4-cyano-3-methoxyphenyl)-1H-benzimidazol-2-yl]amino}phenyl)ethyl]carbamate
-
(2R)-1-cyanobutan-2-yl [(1S)-1-(3-{[6-(4-cyano-3-methoxyphenyl)pyrazine-2-carbonyl]amino}phenyl)ethyl]carbamate
-
(2R)-1-cyanobutan-2-yl [(1S)-1-{3-[2-(3,4-dimethoxyphenoxy)acetamido]phenyl}ethyl]carbamate
-
(2R)-1-cyanobutan-2-yl [(1S)-1-{3-[2-(4-cyano-3-methoxyphenoxy)acetamido]phenyl}ethyl]carbamate
-
(2R)-1-cyanobutan-2-yl [(1S)-1-{3-[3-(4-cyano-3-methoxyphenyl)-2,4-dioxoimidazolidin-1-yl]phenyl}ethyl]carbamate
-
(2R)-1-cyanobutan-2-yl [(1S)-1-{3-[N'-(3,4-dimethoxyphenyl)carbamimidamido]phenyl}ethyl]carbamate
-
(2R)-1-cyanobutan-2-yl {(1S)-1-[3-({[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]carbamoyl}amino)phenyl]ethyl}carbamate
-
(2R)-1-cyanobutan-2-yl {(1S)-1-[3-({[3-methoxy-4-(morpholin-4-yl)phenyl]carbamoyl}amino)phenyl]ethyl}carbamate
-
(2R)-1-cyanobutan-2-yl {(1S)-1-[3-({[3-methoxy-4-(oxan-4-yl)phenyl]carbamoyl}amino)phenyl]ethyl}carbamate
-
(2R)-1-cyanobutan-2-yl {(1S)-1-[3-({[4-(3,6-dihydro-2H-pyran-4-yl)-3-methoxyphenyl]carbamoyl}amino)phenyl]ethyl}carbamate
-
(2R)-1-cyanobutan-2-yl-[(1S)-1-(3-{[(3,4-dimethoxyphenyl)carbamoyl]amino}phenyl)-ethyl] carbamate
-
(2S)-1-cyanobutan-2-yl [(1R)-1-(3-{[(3,4-dimethoxyphenyl)carbamothioyl]amino}phenyl)ethyl]carbamate
-
(2S)-1-cyanobutan-2-yl [(1R)-1-(3-{[(4-cyano-3-methoxyphenyl)carbamothioyl]amino}phenyl)ethyl]carbamate
-
(2S)-1-cyanobutan-2-yl [(1R)-1-{3-[N''-cyano-N'-(4-cyano-3,5-dimethoxyphenyl)carbamimidamido]phenyl}ethyl]carbamate
-
(2S)-1-cyanobutan-2-yl [(1R)-1-{3-[N'-(3,4,5-trimethoxyphenyl)carbamimidamido]phenyl}ethyl]carbamate
-
(2S)-1-cyanobutan-2-yl [(1R)-1-{3-[N'-(4-cyano-3,5-dimethoxyphenyl)carbamimidamido]phenyl}ethyl]carbamate
-
(3aR,4R,6S,7aR)-6-hydroxy-2,2-dimethyl-6-(propylcarbamoyl)hexahydro-2H-1,3-benzodioxol-4-yl (4E)-6-[4-(acetyloxy)-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl]-4-methylhex-4-enoate
-
(3aR,4R,7S,8aR)-7-hydroxy-2,2-dimethyltetrahydro-2H-4,7-methano[1,3]dioxolo[4,5-c]oxepin-6(4H)-one
-
(3aR,5R,7R,7aS)-5,7-dihydroxy-2,2-dimethyl-N-propylhexahydro-2H-1,3-benzodioxole-5-carboxamide
-
(3S)-oxolan-3-yl {[3-({[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]carbamoyl}amino)phenyl]methyl}carbamate
(3S,4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-3,4-dimethylhex-4-enoic acid
-
(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)acetaldehyde
-
(4E)-6-(4,6-dihydroxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enoic acid
derivative of mycophenolic acid. IC50 value for K562 cells proliferation 8.2 microM
(4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methyl-N-(1H-1,2,4-triazol-5-yl)hex-4-enamide
-
(4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methyl-N-[(2R)-2-phenylpropyl]hex-4-enamide
73.94% inhibition at 0.01 mM
(4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methyl-N-[(2S)-2-phenylpropyl]hex-4-enamide
59.15% inhibition at 0.01 mM
(4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methyl-N-[2-(2-methylphenyl)ethyl]hex-4-enamide
84% inhibition at 0.01 mM
(4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methyl-N-[2-(4-methylphenyl)ethyl]hex-4-enamide
73.42% inhibition at 0.01 mM
(4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methyl-N-[2-(pyridin-2-yl)ethyl]hex-4-enamide
59.38% inhibition at 0.01 mM
(4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methyl-N-[2-(pyridin-4-yl)ethyl]hex-4-enamide
57.38% inhibition at 0.01 mM
(4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methyl-N-[3-(morpholin-4-yl)propyl]hex-4-enamide
36.05% inhibition at 0.01 mM
(4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methyl-N-[4-(trifluoromethyl)phenyl]hex-4-enamide
-
(4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methyl-N-{[(1-nitro-4a,9a-dihydroacridin-9-yl)amino]methyl}hex-4-enamide
-
(4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methyl-N-{[(4-nitro-9-oxo-4a,9,9a,10-tetrahydroacridin-1-yl)amino]methyl}hex-4-enamide
-
(4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enal
-
(4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
-
(4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enoic acid
-
(4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-N-(3-methoxyphenyl)-4-methylhex-4-enamide
30.82% inhibition at 0.01 mM
(4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-N-(4-methoxyphenyl)-4-methylhex-4-enamide
54.84% inhibition at 0.01 mM
(4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-N-[2-(4-methoxyphenyl)ethyl]-4-methylhex-4-enamide
96.13% inhibition at 0.01 mM
(4E)-6-[4-(acetyloxy)-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl]-4-methylhex-4-enoic acid
derivative of mycophenolic acid. IC50 value for K562 cells proliferation 0.59 microM
(4E)-N-(2,3-dichlorophenyl)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
-
(4E)-N-(3,4-dichlorophenyl)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
-
(4E)-N-(4-chloro-3-methoxyphenyl)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
-
(4E)-N-(4-chlorophenyl)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
-
(4E)-N-(4-chlorophenyl)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-N,4-dimethylhex-4-enamide
-
(4E)-N-(4-cyanophenyl)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
-
(4E)-N-(4-fluorophenyl)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
-
(4E)-N-hydroxy-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
(4E)-N-[(4-butylphenyl)methyl]-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
93.62% inhibition at 0.01 mM
(4E)-N-[2-(2-chlorophenyl)ethyl]-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
72.04% inhibition at 0.01 mM
(4E)-N-[2-(2H-1,3-benzodioxol-5-yl)ethyl]-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
87.09% inhibition at 0.01 mM
(4E)-N-[2-(4-chlorophenyl)ethyl]-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
81.36% inhibition at 0.01 mM
(4E)-N-[2-(furan-2-yl)ethyl]-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
67.18% inhibition at 0.01 mM
(4E)-N-[4-chloro-3-(trifluoromethyl)phenyl]-6-(4,6-dimethoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
-
(4E)-N-[4-chloro-3-(trifluoromethyl)phenyl]-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
-
(5E)-N-hydroxy-7-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-5-methylhept-5-enamide
-
comparison with inhibition of histone deacetylase and K562 cell proliferation
(E)-N-[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]-1-(thiophen-2-yl)methanimine
-
([[(2E)-4-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-2-methylbut-2-en-1-yl]oxy]methyl)phosphonic acid
-
isozyme IMPDH II IC50: 246 nM
([[(2E)-4-(6-ethyl-4-hydroxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-2-methylbut-2-en-1-yl]oxy]methyl)phosphonic acid
-
isozyme IMPDH II IC50: 23 nM
({hydroxy[2-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)ethoxy]phosphoryl}methyl)phosphonic acid
-
1-(2,2-dimethylpropanoyl)-7'-methoxy-3'-methyl-6'-(1,3-oxazol-5-yl)-1'H-spiro[pyrrolidine-3,2'-quinazolin]-4'(3'H)-one
-
IC50: 0.094 mM, isozyme IMPDH II
1-(3-methylphenyl)-3-[4-(1,3-oxazol-5-yl)phenyl]urea
-
isozyme IMPDH II IC50: 640 nM
1-methyl-6-[(5-phenyl-1,3-oxazol-2-yl)amino]-1H-indole-3-carbonitrile
-
1-tert-butyl 5-methyl (3R,5R)-7'-methoxy-3'-methyl-6'-(1,3-oxazol-5-yl)-4'-oxo-3',4'-dihydro-1H,1'H-spiro[pyrrolidine-3,2'-quinazoline]-1,5-dicarboxylate
-
IC50: 35 nM, isozyme IMPDH II
1-tert-butyl 5-methyl (3R,5S)-7'-methoxy-3'-methyl-6'-(1,3-oxazol-5-yl)-4'-oxo-3',4'-dihydro-1H,1'H-spiro[pyrrolidine-3,2'-quinazoline]-1,5-dicarboxylate
-
IC50: 948 nM, isozyme IMPDH II
1-tert-butyl 5-methyl (3S,5R)-7'-methoxy-3'-methyl-6'-(1,3-oxazol-5-yl)-4'-oxo-3',4'-dihydro-1H,1'H-spiro[pyrrolidine-3,2'-quinazoline]-1,5-dicarboxylate
-
IC50: 35 nM, isozyme IMPDH II
1-tert-butyl 5-methyl (3S,5S)-7'-methoxy-3'-methyl-6'-(1,3-oxazol-5-yl)-4'-oxo-3',4'-dihydro-1H,1'H-spiro[pyrrolidine-3,2'-quinazoline]-1,5-dicarboxylate
-
26% inhibition at 10 micromol, isozyme IMPDH II
1-[(3,4-dichlorophenyl)methyl]-4-[[(naphthalen-1-yl)oxy]methyl]-1H-1,2,3-triazole
0.1% inhibition at 0.01 mM
1-[(3,4-dichlorophenyl)methyl]-4-[[(naphthalen-2-yl)oxy]methyl]-1H-1,2,3-triazole
0.1% inhibition at 0.01 mM
1-[(3-chlorophenyl)methyl]-4-[[(naphthalen-1-yl)oxy]methyl]-1H-1,2,3-triazole
0.1% inhibition at 0.01 mM
1-[(3-chlorophenyl)methyl]-4-[[(naphthalen-2-yl)oxy]methyl]-1H-1,2,3-triazole
0.1% inhibition at 0.01 mM
1-[(3-methoxyphenyl)methyl]-4-[[(naphthalen-1-yl)oxy]methyl]-1H-1,2,3-triazole
30.66% inhibition at 0.01 mM
1-[(3-methoxyphenyl)methyl]-4-[[(naphthalen-2-yl)oxy]methyl]-1H-1,2,3-triazole
24.94% inhibition at 0.01 mM
1-[2-(cyclododecyloxy)-2-oxoethyl]-1-methylpiperidin-1-ium
-
i.e. 5F02, about 40% inhibition at 4 mM, less than 20% inhibition at 1 and 8 mM
1-[3,4-bis(benzyloxy)-5-oxo-2,5-dihydrofuran-2-yl]ethane-1,2-diyl diacetate
-
1-[3-chloro-4-(1,3-oxazol-5-yl)phenyl]-3-(3-methylphenyl)urea
-
isozyme IMPDH II IC50: 43 nM
1-[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]-3-(3-methylphenyl)urea
-
isozyme IMPDH II IC50: 19 nM
1-[4-(4-methyl-1,3-oxazol-5-yl)phenyl]-3-(3-methylphenyl)urea
-
isozyme IMPDH II IC50: 500 nM
1-{5-O-[hydroxy({hydroxy[2-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)ethoxy]phosphoryl}methyl)phosphoryl]-beta-D-ribofuranosyl}-1H-benzimidazol-4-amine
-
2'-methylthiazole-4-carboxamide adenine dinucleotide
-
noncompetitive inhibition, less cytotoxic against K562 tumor cells
2,2,2-trichloroethyl (1-oxo-1,3-dihydro-2-benzofuran-5-yl)carbamate
-
2-(1,3-oxazol-5-yl)-5-[(5-phenyl-1,3-oxazol-2-yl)amino]phenol
-
isozyme IMPDH II IC50: 0.0016 mM
2-(1-benzothiophen-3-yl)-6-methoxy-5-(1,3-oxazol-2-yl)-1H-indole-3-carbaldehyde
-
2-(1-benzothiophen-3-yl)-6-methoxy-5-(1,3-oxazol-5-yl)-1H-indole-3-carbaldehyde
-
2-(dimethylamino)-7-methoxy-6-(1,3-oxazol-5-yl)quinolin-4(1H)-one
-
isozyme IMPDH II IC50: 200 nM
2-(methyl{2-[(2lambda~5~-triaza-1,2-dien-2-yl)acetyl]phenyl}amino)-2-oxoethyl acetate
-
2-([2-[2-(furan-2-yl)phenyl]-4-oxo-4H-1-benzopyran-3-yl]oxy)-N-(1-oxo-1,3-dihydro-2-benzofuran-5-yl)acetamide
0.1% inhibition at 0.01 mM
2-benzyl-7-methoxy-6-(1,3-oxazol-5-yl)quinolin-4(1H)-one
-
isozyme IMPDH II IC50: 180 nM
2-cyano-1-[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]-3-phenylguanidine
-
isozyme IMPDH II IC50: 240 nM
2-ethyl-5'-O-[hydroxy({hydroxy[2-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)ethoxy]phosphoryl}methyl)phosphoryl]adenosine
-
2-ethyl-9-[5-O-[hydroxy(2-[hydroxy[2-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)ethoxy]phosphoryl]ethyl)phosphoryl]-beta-L-ribofuranosyl]-9H-purin-6-amine
inhibition of leukemia K562 cells proliferation, IC50 of 4.0 microM
2-furan-3-yl-7-methoxy-6-(1,3-oxazol-5-yl)quinolin-4(1H)-one
-
isozyme IMPDH II IC50: 32 nM
2-hydroxy-N-[2-(2-[[3-methoxy-4-(1,3-oxazol-4-yl)phenyl]amino]-1,3-oxazol-5-yl)phenyl]-N-methylacetamide
-
isozyme IMPDH II IC50: 41 nM
2-tert-butyl-7-methoxy-6-(1,3-oxazol-5-yl)quinolin-4(1H)-one
-
isozyme IMPDH II IC50: 0.01 mM
2-[(2-{2-[3-methoxy-4-(1,3-oxazol-5-yl)anilino]-1,3-oxazol-5-yl}phenyl)(methyl)amino]-2-oxoethyl acetate
-
2-[(3-ethyl-4-oxo-3,4-dihydrothieno[3,2-d]pyrimidin-2-yl)sulfanyl]-N-(4-methoxyphenyl)acetamide
-
2-[4-([1-[(3,4-dichlorophenyl)methyl]-1H-1,2,3-triazol-4-yl]methoxy)phenyl]-5-methyl-1,3,4-oxadiazole
0.1% inhibition at 0.01 mM
2-[4-([1-[(3-chlorophenyl)methyl]-1H-1,2,3-triazol-4-yl]methoxy)phenyl]-5-methyl-1,3,4-oxadiazole
0.1% inhibition at 0.01 mM
2-[4-([1-[(3-methoxyphenyl)methyl]-1H-1,2,3-triazol-4-yl]methoxy)phenyl]-5-methyl-1,3,4-oxadiazole
0.1% inhibition at 0.01 mM
2-[methyl[2-(2-[[3-(1,3-oxazol-5-yl)-1H-indol-6-yl]amino]-1,3-oxazol-5-yl)phenyl]amino]-2-oxoethyl acetate
-
2-[[2-(2-chlorophenyl)-4-oxo-4H-1-benzopyran-3-yl]oxy]-N-(1-oxo-1,3-dihydro-2-benzofuran-5-yl)acetamide
0.1% inhibition at 0.01 mM
2-[[2-(3,4-dimethoxyphenyl)-4-oxo-4H-1-benzopyran-3-yl]oxy]-N-(1-oxo-1,3-dihydro-2-benzofuran-5-yl)acetamide
34.45% inhibition at 0.01 mM
2-[[2-(3,4-dimethoxyphenyl)-4-oxo-4H-1-benzopyran-3-yl]oxy]-N-(naphthalen-1-yl)acetamide
0.1% inhibition at 0.01 mM
2-[[2-(4-methoxyphenyl)-4-oxo-4H-1-benzopyran-3-yl]oxy]-N-(1-oxo-1,3-dihydro-2-benzofuran-5-yl)acetamide
56.81% inhibition at 0.01 mM
2-[[2-(4-methoxyphenyl)-4-oxo-4H-1-benzopyran-3-yl]oxy]-N-(naphthalen-1-yl)acetamide
2.1% inhibition at 0.01 mM
2-[[2-(4-methylphenyl)-4-oxo-4H-1-benzopyran-3-yl]oxy]-N-(1-oxo-1,3-dihydro-2-benzofuran-5-yl)acetamide
0.1% inhibition at 0.01 mM
3'-methylthiazole-4-carboxamide adenine dinucleotide
-
noncompetitive inhibition, less cytotoxic against K562 tumor cells
3'-[N''-cyano-N'-(4-cyano-3-methoxyphenyl)carbamimidamido][1,1'-biphenyl]-3-carboxylic acid
-
3-(2-{2-[3-methoxy-4-(1,3-oxazol-5-yl)anilino]-1,3-oxazol-5-yl}phenyl)-1-(morpholin-4-yl)butan-2-one
i.e. BMS-337197
3-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)propyl (4-chlorophenyl)carbamate
-
3-cyanoindole-based inhibitors
-
synthesis and initial structureactivity relationships of 3-cyanoindole-based inhibitors with isozyme IMPDH II, IC50: 33-420 nM, comparison to other inhibitor structural classes, overview
-
3-hydroxy-N-methyl-N-[2-(2-[[3-methyl-4-(1,3-oxazol-5-yl)phenyl]amino]-1,3-oxazol-5-yl)phenyl]propanamide
-
isozyme IMPDH II IC50: 100 nM
3-hydroxy-N-[2-(2-[[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]amino]-1,3-oxazol-5-yl)phenyl]-N-methylpropanamide
-
isozyme IMPDH II IC50: 21 nM
3-phenyl quinolone derivatives
-
several, isozyme IMPDH II IC50: 5-160 nM, overview
-
3-{3-[N''-cyano-N'-(4-cyano-3-methoxyphenyl)carbamimidamido]phenyl}propanoic acid
-
4-[[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]amino]-6-phenyl-1,3,5-triazin-2-ol
-
5'-deoxy-5'-[(3-{[(4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enoyl]amino}-2-oxopropyl)amino]adenosine
-
5'-O-({[2-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]sulfamoyl}methanesulfonyl)adenosine
-
5'-O-[hydroxy({hydroxy[2-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)ethoxy]phosphoryl}methyl)phosphoryl]adenosine
-
6-((E)-4-(((1-(50-deoxy-adenosin-50-yl)-1H-1,2,3-triazol-4-yl)-methyl)amino)-3-methylbut-2-en-1-yl)-7-hydroxy-5-methoxy-4-methylisobenzofuran-1(3H)-one
-
6-((E)-4-(4-(adenosin-50-yl)methyl-1H-1,2,3-triazol-1-yl)-3-methylbut-2-en-1-yl)-7-hydroxy-5-methoxy-4-methylisobenzofuran-1(3H)-one
-
6-thioguanosine
-
expression of isoform IMPDH2 increases modestly in response to 6-thioguanosine exposure. However, the basal enzyme activity decreases when the cells are exposed to a proliferation-blocking 6-thioguanosine concentration
6-{(2E)-4-[4-({[(2S,5R)-5-(6-amino-7,8-dihydro-9H-purin-9-yl)oxolan-2-yl]methoxy}methyl)-1H-1,2,3-triazol-1-yl]-3-methylbut-2-en-1-yl}-7-hydroxy-5-methoxy-4-methyl-2-benzofuran-1(3H)-one
-
7'-methoxy-3'-methyl-6'-(1,3-oxazol-5-yl)-1'H-spiro[cyclopentane-1,2'-quinazolin]-4'(3'H)-one
-
IC50: 328 nM, isozyme IMPDH II
7'-methoxy-3'-methyl-6'-(1,3-oxazol-5-yl)-1-(piperidin-1-ylcarbonyl)-1'H-spiro[pyrrolidine-3,2'-quinazolin]-4'(3'H)-one
-
IC50: 0.068 mM, isozyme IMPDH II
7'-methoxy-3'-methyl-6'-(1,3-oxazol-5-yl)-2,3,5,6-tetrahydro-1'H-spiro[pyran-4,2'-quinazolin]-4'(3'H)-one
-
IC50: 526 nM, isozyme IMPDH II
7'-methoxy-3'-methyl-6'-(1,3-oxazol-5-yl)-4'-oxo-N-phenyl-3',4'-dihydro-1H,1'H-spiro[pyrrolidine-3,2'-quinazoline]-1-carboxamide
-
IC50: 0.393 mM, isozyme IMPDH II
7'-methoxy-3'-methyl-6'-(1,3-oxazol-5-yl)-4,6-dihydro-1'H-spiro[cyclopenta[b]thiophene-5,2'-quinazolin]-4'(3'H)-one
-
IC50: 96 nM, isozyme IMPDH II
7'-methoxy-3'-methyl-N,N-bis(1-methylethyl)-6'-(1,3-oxazol-5-yl)-4'-oxo-3',4'-dihydro-1H,1'H-spiro[pyrrolidine-3,2'-quinazoline]-1-carboxamide
-
IC50: 0.071 mM, isozyme IMPDH II
7'-methoxy-N,3'-dimethyl-6'-(1,3-oxazol-5-yl)-4'-oxo-N-phenyl-3',4'-dihydro-1H,1'H-spiro[pyrrolidine-3,2'-quinazoline]-1-carboxamide
-
IC50: 0.064 mM, isozyme IMPDH II
7-hydroxy-5-methoxy-4-methyl-6-(3-methylbut-2-en-1-yl)-2-benzofuran-1(3H)-one
-
isozyme IMPDH II IC50: 254 nM
7-hydroxy-5-methoxy-4-methyl-6-[(2E)-3-methyl-4-(2lambda~5~-triaza-1,2-dien-2-yl)but-2-en-1-yl]-2-benzofuran-1(3H)-one
-
7-hydroxy-5-methoxy-4-methyl-6-{(2E)-3-methyl-6-[(2R)-oxiran-2-yl]-6-oxohex-2-en-1-yl}-2-benzofuran-1(3H)-one
-
7-hydroxy-5-methoxy-4-methyl-6-{(2E)-3-methyl-6-[(2S)-oxiran-2-yl]-6-oxohex-2-en-1-yl}-2-benzofuran-1(3H)-one
-
7-hydroxy-5-methoxy-6-[(2E)-4-methoxy-3-methylbut-2-en-1-yl]-4-methyl-2-benzofuran-1(3H)-one
-
isozyme IMPDH II IC50: 273 nM
7-hydroxy-6-[(2E)-6-hydroxy-3-methylocta-2,7-dien-1-yl]-5-methoxy-4-methyl-2-benzofuran-1(3H)-one
-
7-methoxy-2,2,3-trimethyl-6-(1,3-oxazol-5-yl)-2,3-dihydroquinazolin-4(1H)-one
-
IC50: 192 nM, isozyme IMPDH II
7-methoxy-2,2-dimethyl-6-(1,3-oxazol-5-yl)-3-(2-pyridin-4-ylethyl)-2,3-dihydroquinazolin-4(1H)-one
-
IC50: 300 nM, isozyme IMPDH II
7-methoxy-2,3-dimethyl-6-(1,3-oxazol-5-yl)-2-[(E)-2-phenylethenyl]-2,3-dihydroquinazolin-4(1H)-one
-
IC50: 49 nM, isozyme IMPDH II
7-methoxy-2-(3-methylphenyl)-6-(1,3-oxazol-5-yl)quinolin-4(1H)-one
-
7-methoxy-2-(methylamino)-6-(1,3-oxazol-5-yl)quinolin-4(1H)-one
-
isozyme IMPDH II IC50: 220 nM
7-methoxy-2-methyl-6-(1,3-oxazol-5-yl)quinolin-4(1H)-one
-
isozyme IMPDH II IC50: 110 nM
7-methoxy-3-methyl-6-(1,3-oxazol-5-yl)-2-phenylquinolin-4(1H)-one
-
isozyme IMPDH II IC50: 65 nM
7-methoxy-3-methyl-6-(1,3-oxazol-5-yl)quinazoline-2,4(1H,3H)-dione
-
IC50: 104 nM, isozyme IMPDH II
7-methoxy-6-(1,3-oxazol-4-yl)-2-phenylquinolin-4(1H)-one
-
isozyme IMPDH II IC50: 210 nM
7-methoxy-6-(1,3-oxazol-5-yl)-2-(1,3-thiazol-4-yl)quinolin-4(1H)-one
-
isozyme IMPDH II IC50: 34 nM
7-methoxy-6-(1,3-oxazol-5-yl)-2-phenoxyquinolin-4(1H)-one
-
isozyme IMPDH II IC50: 8 nM
7-methoxy-6-(1,3-oxazol-5-yl)-2-phenylquinolin-4(1H)-one
-
isozyme IMPDH II IC50: 8 nM
7-methoxy-6-(1,3-oxazol-5-yl)-2-pyridin-2-ylquinolin-4(1H)-one
-
isozyme IMPDH II IC50: 43 nM
7-methoxy-6-(1,3-oxazol-5-yl)-2-pyridin-3-ylquinolin-4(1H)-one
-
isozyme IMPDH II IC50: 70 nM
7-methoxy-6-(1,3-oxazol-5-yl)-2-pyridin-4-ylquinolin-4(1H)-one
-
isozyme IMPDH II IC50: 46 nM
7-methoxy-6-(1,3-oxazol-5-yl)-2-thiophen-2-ylquinolin-4(1H)-one
-
isozyme IMPDH II IC50: 63 nM
7-methoxy-6-(1,3-oxazol-5-yl)-2-thiophen-3-ylquinolin-4(1H)-one
-
isozyme IMPDH II IC50: 9 nM
7-methoxy-6-(1,3-oxazol-5-yl)-2-thioxo-2,3-dihydroquinazolin-4(1H)-one
-
IC50: 303 nM
7-methoxy-6-(1,3-oxazol-5-yl)-3-(2-pyridin-4-ylethyl)-2-thioxo-2,3-dihydroquinazolin-4(1H)-one
-
7-methoxy-6-(1,3-oxazol-5-yl)-3-[2-(pyridin-4-yl)ethyl]-2-sulfanylidene-2,3-dihydroquinazolin-4(1H)-one
-
9-(5-deoxy-5-([(([2-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)ethoxy]sulfonyl)methyl)sulfonyl]amino)-b-L-ribofuranosyl)-2-ethyl-9H-purin-6-amine
-
9-(5-deoxy-5-([(([2-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)ethoxy]sulfonyl)methyl)sulfonyl]amino)-b-L-ribofuranosyl)-2-ethynyl-9H-purin-6-amine
-
9-(5-deoxy-5-([(([2-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)ethoxy]sulfonyl)methyl)sulfonyl]amino)-b-L-ribofuranosyl)-2-phenyl-9H-purin-6-amine
-
9-(5-deoxy-5-([(([2-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)ethoxy]sulfonyl)methyl)sulfonyl]amino)-b-L-ribofuranosyl)-9H-purin-6-amine
-
9-(5-O-[hydroxy[([hydroxy[2-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)ethoxy]phosphoryl]oxy)methyl]phosphoryl]-beta-L-ribofuranosyl)-9H-purin-6-amine
AVN944
induces caspase-independent apoptosis in multiple myeloma cell lines and displays antiproliferative activity against both androgen-dependent and androgen-independent prostate cancer cell lines
beta-methylene thiazole 4-carboxamide adenine dinucleotide
-
i.e. beta-Me-TAD or CH2-TAD
C4-mycophenolic adenine dinucleotide
-
methylenephosphophosphonate analogue of mycophenolic adenine dinucleotide
curcumin
-
significantly reduces the level of GTP and reduces the rate of cell growth
dimethyl (2-[[(2E)-4-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-2-methylbut-2-en-1-yl]amino]ethyl)phosphonate
-
isozyme IMPDH II IC50: above 0.001 mM
dimethyl 1-{(2Z)-2-[3,4-bis(benzyloxy)-5-oxofuran-2(5H)-ylidene]ethyl}-4,5-dihydro-1H-imidazole-4,5-dicarboxylate
-
dimethyl [(2E)-4-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-2-methylbut-2-en-1-yl]phosphonate
-
isozyme IMPDH II IC50: 289 nM
ethyl (2E)-3-[3-methoxy-4-(1,3-oxazol-5-yl)anilino]-3-phenylprop-2-enoate
-
ethyl (2E)-3-[4-({[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]carbamoyl}amino)phenyl]prop-2-enoate
-
ethyl (4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enoyl carbonate
-
ethyl 7'-methoxy-3'-methyl-6'-(1,3-oxazol-5-yl)-4'-oxo-3',4'-dihydro-1H,1'H-spiro[pyrrolidine-3,2'-quinazoline]-1-carboxylate
-
IC50: 0.08 mM, isozyme IMPDH II
methyl (4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enoate
derivative of mycophenolic acid. IC50 value for K562 cells proliferation 0.73 microM
methyl N-[(4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enoyl]alaninate
-
mycophenolic 2-ethyladenosin-5'-yl-difluoromethylenebis(phosphonate)
potent, sub-micromolar inhibitor of leukemia K562 cells proliferation, IC50 of 0.45 microM
mycophenolic 2-ethyladenosin-5'-yl-methylenebis(phosphonate)
inhibition of leukemia K562 cells proliferation, IC50 of 1.0 microM
mycophenolic acid glucuronide
-
80% inhibition at 0.2 mM, human plasma or serum reduces the inhibition
mycophenolic hydroxamic acid
-
comparison with inhibition of histone deacetylase and K562 cell proliferation
N''-cyano-N-(3'-cyano[1,1'-biphenyl]-3-yl)-N'-(4-cyano-3-methoxyphenyl)guanidine
-
N''-cyano-N-(4'-cyano[1,1'-biphenyl]-3-yl)-N'-(4-cyano-3-methoxyphenyl)guanidine
-
N''-cyano-N-(4-cyano-3-methoxyphenyl)-N'-(2'-fluoro[1,1'-biphenyl]-3-yl)guanidine
-
N''-cyano-N-(4-cyano-3-methoxyphenyl)-N'-(3'-fluoro[1,1'-biphenyl]-3-yl)guanidine
-
N''-cyano-N-(4-cyano-3-methoxyphenyl)-N'-(4'-fluoro[1,1'-biphenyl]-3-yl)guanidine
-
N''-cyano-N-(4-cyano-3-methoxyphenyl)-N'-[3'-(trifluoromethyl)[1,1'-biphenyl]-3-yl]guanidine
-
N''-cyano-N-(4-cyano-3-methoxyphenyl)-N'-[3-(1-hydroxyethenyl)phenyl]guanidine
-
N''-cyano-N-(4-cyano-3-methoxyphenyl)-N'-[3-(2-hydroxyprop-2-en-1-yl)phenyl]guanidine
-
N''-cyano-N-(4-cyano-3-methoxyphenyl)-N'-[3-(2-methyl-2H-tetrazol-5-yl)phenyl]guanidine
-
N''-cyano-N-(4-cyano-3-methoxyphenyl)-N'-{3-[(1-methyl-1H-tetrazol-5-yl)methyl]phenyl}guanidine
-
N''-cyano-N-(4-cyano-3-methoxyphenyl)-N'-{3-[(2-methyl-2H-tetrazol-5-yl)methyl]phenyl}guanidine
-
N,7'-dimethoxy-N,3'-dimethyl-6'-(1,3-oxazol-5-yl)-4'-oxo-3',4'-dihydro-1H,1'H-spiro[pyrrolidine-3,2'-quinazoline]-1-carboxamide
-
IC50: 0.079 mM, isozyme IMPDH II
N,N-diethyl-7'-methoxy-3'-methyl-6'-(1,3-oxazol-5-yl)-4'-oxo-3',4'-dihydro-1H,1'H-spiro[pyrrolidine-3,2'-quinazoline]-1-carboxamide
-
IC50: 0.045 mM, isozyme IMPDH II
N-(1-oxo-1,3-dihydro-2-benzofuran-5-yl)-2-([4-oxo-2-[2-(thiophen-2-yl)phenyl]-4H-1-benzopyran-3-yl]oxy)acetamide
0.1% inhibition at 0.01 mM
N-(1-oxo-1,3-dihydro-2-benzofuran-5-yl)-2-[[4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-1-benzopyran-3-yl]oxy]acetamide
0.1% inhibition at 0.01 mM
N-(2,4-difluorophenyl)-7'-methoxy-N,3'-dimethyl-6'-(1,3-oxazol-5-yl)-4'-oxo-3',4'-dihydro-1H,1'H-spiro[pyrrolidine-3,2'-quinazoline]-1-carboxamide
-
IC50: 0.051 mM, isozyme IMPDH II
N-(2-{2-[3-methoxy-4-(1,3-oxazol-5-yl)anilino]-1,3-oxazol-5-yl}phenyl)-N-methyl-2-(morpholin-4-yl)acetamide
-
N-(4-bromophenyl)-2-[[2-(4-methoxyphenyl)-4-oxo-4H-1-benzopyran-3-yl]oxy]acetamide
0.1% inhibition at 0.01 mM
N-(4-bromophenyl)-2-[[2-(4-methylphenyl)-4-oxo-4H-1-benzopyran-3-yl]oxy]acetamide
0.1% inhibition at 0.01 mM
N-(4-chlorophenyl)-2-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)acetamide
-
N-(4-chlorophenyl)-4-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)butanamide
-
N-(4-methoxyphenyl)-2-(3-methyl-4-oxo-3,4-dihydrophthalazin-1-yl)acetamide
-
N-(4-methoxyphenyl)-2-[2-(1,3-thiazol-4-yl)-1H-benzimidazol-1-yl]acetamide
-
N-(naphthalen-1-yl)-2-[(4-oxo-2-phenyl-4H-1-benzopyran-3-yl)oxy]acetamide
0.1% inhibition at 0.01 mM
N-(naphthalen-1-yl)-2-[[4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-1-benzopyran-3-yl]oxy]acetamide
16.54% inhibition at 0.01 mM
N-(naphthalen-2-yl)-2-[2-(pyridin-2-yl)-1H-benzimidazol-1-yl]acetamide
C91, 0.197% inhibition at 0.01 mM
N-ethyl-7'-methoxy-3'-methyl-6'-(1,3-oxazol-5-yl)-4'-oxo-3',4'-dihydro-1H,1'H-spiro[pyrrolidine-3,2'-quinazoline]-1-carboxamide
-
IC50: 0.119 mM, isozyme IMPDH II
N-hydroxy-N'-[3-methoxy-4-(1,3-oxazol-2-yl)phenyl]octanediamide
-
comparison with inhibition of histone deacetylase and K562 cell proliferation
N-methyl-N'-[4-(1,3-oxazol-5-yl)phenyl]-6-phenyl-1,3,5-triazine-2,4-diamine
-
isozyme IMPDH II IC50: 0.005 mM
N-methyl-N'-[4-(4-methyl-1,3-oxazol-5-yl)phenyl]-6-phenyl-1,3,5-triazine-2,4-diamine
-
isozyme IMPDH II IC50: 0.005 mM
N-methyl-N-[2-(2-[[3-methyl-4-(1,3-oxazol-5-yl)phenyl]amino]-1,3-oxazol-5-yl)phenyl]-3-morpholin-4-ylpropanamide
-
isozyme IMPDH II IC50: 45 nM
N-tert-butyl-N'-[3-chloro-4-(1,3-oxazol-5-yl)phenyl]ethanediamide
-
isozyme IMPDH II IC50: 55 nM
N-tert-butyl-N'-[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]ethanediamide
-
isozyme IMPDH II IC50: 10 nM
N-tert-butyl-N'-[4-(1,3-oxazol-5-yl)phenyl]ethanediamide
-
isozyme IMPDH II IC50: 0.005 mM
N-tert-butyl-N'-[4-(4-methyl-1,3-oxazol-5-yl)phenyl]ethanediamide
-
isozyme IMPDH II IC50: 0.005 mM
N-[(4-fluorophenyl)(1-methyl-1H-imidazol-2-yl)methyl]-2-methyl-3-(1,2,4-thiadiazol-5-yl)-1H-indole-6-carboxamide
-
N-[(4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enoyl]alanine
-
N-[1-[6-(4-ethylpiperazin-1-yl)pyridin-3-yl]-1-methylethyl]-2-fluoro-9-oxo-9,10-dihydroacridine-3-carboxamide
-
N-[2-(2-[[3-(chloromethyl)-4-(1,3-oxazol-5-yl)phenyl]amino]-1,3-oxazol-5-yl)phenyl]-N-methyl-3-morpholin-4-ylpropanamide
-
isozyme IMPDH II IC50: 47 nM
N-[2-(2-[[3-bromo-4-(1,3-oxazol-5-yl)phenyl]amino]-1,3-oxazol-5-yl)phenyl]-3-hydroxy-N-methylpropanamide
-
isozyme IMPDH II IC50: 28 nM
N-[2-(2-[[3-bromo-4-(1,3-oxazol-5-yl)phenyl]amino]-1,3-oxazol-5-yl)phenyl]-N-methyl-3-morpholin-4-ylpropanamide
-
isozyme IMPDH II IC50: 21 nM
N-[2-(2-[[3-chloro-4-(1,3-oxazol-5-yl)phenyl]amino]-1,3-oxazol-5-yl)phenyl]-3-hydroxy-N-methylpropanamide
-
isozyme IMPDH II IC50: 48 nM
N-[2-(2-[[3-ethyl-4-(1,3-oxazol-5-yl)phenyl]amino]-1,3-oxazol-5-yl)phenyl]-3-hydroxy-N-methylpropanamide
-
isozyme IMPDH II IC50: 310 nM
N-[2-(2-[[3-ethyl-4-(1,3-oxazol-5-yl)phenyl]amino]-1,3-oxazol-5-yl)phenyl]-N-methyl-3-morpholin-4-ylpropanamide
-
isozyme IMPDH II IC50: 21 nM
N-[2-(2-[[3-methoxy-4-(1,3-oxazol-4-yl)phenyl]amino]-1,3-oxazol-5-yl)phenyl]-N-methyl-2-morpholin-4-ylacetamide
-
isozyme IMPDH II IC50: 91 nM
N-[2-(2-[[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]amino]-1,3-oxazol-5-yl)phenyl]-N-methyl-2-morpholin-4-ylacetamide
-
N-[2-(2-[[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]amino]-1,3-oxazol-5-yl)phenyl]-N-methyl-3-morpholin-4-ylpropanamide
-
isozyme IMPDH II IC50: 16 nM
N-[2-(hydroxymethyl)cyclopentyl]-N'-[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]propanediamide
-
N-[2-chloro-3-methoxy-4-(1,3-oxazol-5-yl)phenyl]-5-phenyl-1,3-oxazol-2-amine
-
isozyme IMPDH II IC50: 0.005 mM
N-[2-chloro-5-methoxy-4-(1,3-oxazol-5-yl)phenyl]-5-phenyl-1,3-oxazol-2-amine
-
isozyme IMPDH II IC50: 0.0016 mM
N-[2-fluoro-5-methoxy-4-(1,3-oxazol-5-yl)phenyl]-5-phenyl-1,3-oxazol-2-amine
-
isozyme IMPDH II IC50: 0.005 mM
N-[3-bromo-4-(1,3-oxazol-5-yl)phenyl]-N'-tert-butylethanediamide
-
isozyme IMPDH II IC50: 50 nM
N-[3-chloro-4-(1,3-oxazol-4-yl)phenyl]-5-phenyl-1,3-oxazol-2-amine
-
isozyme IMPDH II IC50: 0.005 mM
N-[3-chloro-4-(1,3-oxazol-5-yl)phenyl]-5-phenyl-1,3-oxazol-2-amine
-
isozyme IMPDH II IC50: 88 nM
N-[3-chloro-4-(1,3-oxazol-5-yl)phenyl]-N'-methyl-6-phenyl-1,3,5-triazine-2,4-diamine
-
isozyme IMPDH II IC50: 340 nM
N-[3-ethoxy-4-(1,3-oxazol-5-yl)phenyl]-5-phenyl-1,3-oxazol-2-amine
-
isozyme IMPDH II IC50: 0.010 mM
N-[3-methoxy-4-(1,3-oxazol-2-yl)phenyl]-5-phenyl-1,3-oxazol-2-amine
-
isozyme IMPDH II IC50: 190 nM
N-[3-methoxy-4-(1,3-oxazol-4-yl)phenyl]-5-phenyl-1,3-oxazol-2-amine
-
isozyme IMPDH II IC50: 57 nM
N-[3-methoxy-4-(1,3-oxazol-4-yl)phenyl]-N'-methyl-6-phenyl-1,3,5-triazine-2,4-diamine
-
isozyme IMPDH II IC50: 0.0016 mM
N-[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]-5-phenyl-1,3-oxazol-2-amine
-
isozyme IMPDH II IC50: 20 nM
N-[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]-N'-methyl-6-phenyl-1,3,5-triazine-2,4-diamine
-
isozyme IMPDH II IC50: 76 nM
N-[3-methoxy-4-(1H-1,2,4-triazol-1-yl)phenyl]-5-phenyl-1,3-oxazol-2-amine
-
isozyme IMPDH II IC50: 410 nM
N-[3-methoxy-4-(2-methyl-1,3-oxazol-5-yl)phenyl]-5-phenyl-1,3-oxazol-2-amine
-
isozyme IMPDH II IC50: 0.002 mM
N-[3-methoxy-4-(4-methyl-1,3-oxazol-5-yl)phenyl]-5-phenyl-1,3-oxazol-2-amine
-
isozyme IMPDH II IC50: 0.005 mM
N-[3-methyl-4-(1,3-oxazol-4-yl)phenyl]-5-phenyl-1,3-oxazol-2-amine
-
isozyme IMPDH II IC50: 0.005 mM
N-[4-(1,3-oxazol-4-yl)phenyl]-5-phenyl-1,3-oxazol-2-amine
-
isozyme IMPDH II IC50: 0.005 mM
N-[4-(1,3-oxazol-5-yl)phenyl]-5-phenyl-1,3-oxazol-2-amine
-
isozyme IMPDH II IC50: 0.005 mM
N-[4-(2,4-dimethyl-1,3-oxazol-5-yl)phenyl]-5-phenyl-1,3-oxazol-2-amine
-
isozyme IMPDH II IC50: 0.002 mM
N-[4-(4-methyl-1,3-oxazol-5-yl)phenyl]-5-phenyl-1,3-oxazol-2-amine
-
isozyme IMPDH II IC50: 0.005 mM
N-[4-chloro-3-(trifluoromethyl)phenyl]-3-[(1R,2S)-2-[(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)methyl]-1-methylcyclopropyl]propanamide
-
N-[4-chloro-3-(trifluoromethyl)phenyl]-3-[(1S,2R)-2-[(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)methyl]-1-methylcyclopropyl]propanamide
-
N-[4-chloro-3-(trifluoromethyl)phenyl]-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhexanamide
-
N-{2-[6-(4-ethylpiperazin-1-yl)pyridin-3-yl]propan-2-yl}-2-fluoro-9-oxo-4a,9,9a,10-tetrahydroacridine-3-carboxamide
-
N-{2-[6-(4-ethylpiperazin-1-yl)pyridin-3-yl]propan-2-yl}-2-fluoro-9-oxo-9,10-dihydroacridine-3-carboxamide
-
N1-methyl-N~2~-(1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethanediamide
-
N~1~-hydroxy-N~8~-[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]octanediamide
-
oxolan-3-yl {[3-({[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]carbamoyl}amino)phenyl]methyl}carbamate
-
P1-(7-hydroxy-6-(ethyl-2-yl)-5-methoxy-4-methylphthalan-1-one)methylenephospho-P2-(adenosin-5'-yl)phosphonate
-
-
P1-(adenosine-5'-yl)methylenephospho-P2-(7-hydroxy-6-(ethyl-2-yl)-5-methoxy-4-methylphthalan-1-one)phosphonate
-
-
P1-(tiazofurin-5'-yl)-P2-(2-aminoadenosin-5'-yl) diphosphate
-
comparison with inhibition of alcohol dehydrogenase, malate dehydrogenase, lactate dehydrogenase and K562 cell proliferation
P1-(tiazofurin-5'-yl)-P2-(2-ethyladenosin-5'-yl) diphosphate
-
comparison with inhibition of alcohol dehydrogenase, malate dehydrogenase, lactate dehydrogenase and K562 cell proliferation
P1-(tiazofurin-5'-yl)-P2-(2-ethynyladenosin-5'-yl) diphosphate
-
comparison with inhibition of alcohol dehydrogenase, malate dehydrogenase, lactate dehydrogenase and K562 cell proliferation
P1-(tiazofurin-5'-yl)-P2-(2-iodoadenosin-5'-yl) diphosphate
-
comparison with inhibition of alcohol dehydrogenase, malate dehydrogenase, lactate dehydrogenase and K562 cell proliferation
P1-(tiazofurin-5'-yl)-P2-(2-phenyladenosin-5'-yl) diphosphate
-
comparison with inhibition of alcohol dehydrogenase, malate dehydrogenase, lactate dehydrogenase and K562 cell proliferation
P1-(tiazofurin-5'-yl)-P2-(adenosin-5'-yl) diphosphate
-
comparison with inhibition of alcohol dehydrogenase, malate dehydrogenase, lactate dehydrogenase and K562 cell proliferation
P1-[7-hydroxy-6-(hydroxyethyl)-5-methoxy-4-methylphthtalan-1-one-2-yl]-P2-(2-ethyladenosin-5'-yl)methylenebis(phosphonate)
P1-[7-hydroxy-6-(hydroxyethyl)-5-methoxy-4-methylphthtalan-1-one-2-yl]-P2-(2-phenyladenosin-5'-yl)methylenebis(phosphonate)
-
P1-[7-hydroxy-6-(hydroxyethyl)-5-methoxy-4-methylphthtalan-1-one-2-yl]-P2-(adenosin-5'-yl)methylenebis(phosphonate)
-
phenyl N'-cyano-N-(3-[cyano[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]carbamimidamido]benzyl)imidocarbamate
-
propan-2-yl {3-[N''-cyano-N'-(4-cyano-3-methoxyphenyl)carbamimidamido]phenoxy}acetate
-
quinazolinedione derivatives
-
several derivatives, synthesis and inhibitory values, overview
-
quinazolinethione derivatives
-
several derivatives, synthesis and inhibitory values, overview
-
S-[(4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-en-1-yl] ethanethioate
-
tert-butyl 7'-methoxy-3'-methyl-6'-(1,3-oxazol-5-yl)-4'-oxo-3',4'-dihydro-1H,1'H-spiro[pyrrolidine-3,2'-quinazoline]-1-carboxylate
-
IC50: 104 nM, isozyme IMPDH II
tert-butyl methyl (1S,4S)-7'-methoxy-3'-methyl-6'-(1,3-oxazol-5-yl)-4'-oxo-3',4'-dihydro-1'H-spiro[cyclopentane-1,2'-quinazoline]-3,4-dicarboxylate
-
thiazofurin-5'-yl-2-ethyladenosin-5'-yl-difluromethylene bis(phosphonate)
inhibition of leukemia K562 cells proliferation, IC50 of 4.7 microM
[(1E,3E)-5-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-3-methylpenta-1,3-dien-1-yl]phosphonic acid
-
isozyme IMPDH II IC50: 506 nM
[(2E)-4-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-2-methylbut-2-en-1-yl]phosphonic acid
-
isozyme IMPDH II IC50: 168 nM
[(2E)-4-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-2-methylbut-2-en-1-yl]phosphoramidic acid
-
isozyme IMPDH II IC50: above 0.001 mM
[(2S,5R)-5-(6-amino-7,8-dihydro-9H-purin-9-yl)oxolan-2-yl]methyl cyanate
-
[(3E)-5-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-3-methylpent-3-en-1-yl]phosphonic acid
-
isozyme IMPDH II IC50: 96 nM
[(3E)-5-(6-ethyl-4-hydroxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-3-methylpent-3-en-1-yl]phosphonic acid
-
isozyme IMPDH II IC50: 20 nM
[(4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-en-1-yl]phosphonic acid
-
isozyme IMPDH II IC50: 86 nM
{3-[N''-cyano-N'-(4-cyano-3-methoxyphenyl)carbamimidamido]phenoxy}acetic acid
-
(4E)-N-hydroxy-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
-
(4E)-N-hydroxy-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
derivative of mycophenolic acid. IC50 value for K562 cells proliferation 2.1 microM
benzamide riboside
displays skeletal muscle toxicity in preclinical trials, which limits its utility
benzamide riboside
inhibitory activity is higher than tiazofurin and lower than selenazofurin
Mycophenolic acid
is a uncompetitive inhibitor of IMPDH with respect to both inosine 5'-phosphate and NAD+, inhibits IMPDH by trapping the covalent intermediate. It it is easily converted to mycophenolic acid-7-O-glucuronide, which limits the inhibitory efficacy and higher doses are therefore needed in order to maintain appropriate therapeutic levels
Mycophenolic acid
inhibition of leukemia K562 cells proliferation, IC50 of 7.7 microM
ribavirin
1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide, a prodrug of corresponding 5-monophosphate, which as a competitive inhibitor interacts with the IMP domain of IMPDH
(2E)-3-furan-2-yl-N-[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]prop-2-enamide
-
(2E)-3-furan-2-yl-N-[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]prop-2-enamide
-
isozyme IMPDH II IC50: 28 nM
(3S)-oxolan-3-yl {[3-({[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]carbamoyl}amino)phenyl]methyl}carbamate
-
(3S)-oxolan-3-yl {[3-({[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]carbamoyl}amino)phenyl]methyl}carbamate
i.e. VX-148, structure-activity relationship analysis, overview
(4E)-N-hydroxy-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
-
(4E)-N-hydroxy-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
derivative of mycophenolic acid. IC50 value for K562 cells proliferation 2.1 microM
9-(5-O-[hydroxy[([hydroxy[2-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)ethoxy]phosphoryl]oxy)methyl]phosphoryl]-beta-L-ribofuranosyl)-9H-purin-6-amine
homology modeling
9-(5-O-[hydroxy[([hydroxy[2-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)ethoxy]phosphoryl]oxy)methyl]phosphoryl]-beta-L-ribofuranosyl)-9H-purin-6-amine
inhibition of leukemia K562 cells proliferation, IC50 of 71.3 microM
benzamide riboside
displays skeletal muscle toxicity in preclinical trials, which limits its utility
benzamide riboside
inhibitory activity is higher than tiazofurin and lower than selenazofurin
C2-mycophenolic adenine dinucleotide
-
methylenephosphophosphonate analogue of mycophenolic adenine dinucleotide
imidazo[4,5-e][1,4]diazapine
fat base nucleotide, inosine 5'-phosphate but not NAD+ protects against inhibition
Mycophenolic acid
-
-
Mycophenolic acid
-
50% inhibition at 0.00025 mM, human plasma or serum reduces the inhibition
Mycophenolic acid
-
enzyme inhibition by mycophenolic acid impairs maturation and function of dendritic cells
Mycophenolic acid
-
exerts immunosuppression through inhibition of the enzyme in lymphocytes, inhibitory potency in vivo, overview, prodrug is mycophenolate mofetil
Mycophenolic acid
-
IC50: 99.2 nM with umbilical vein endothelial cells, 128 nM with Jurkat cells, inhibits the enzyme in vivo and in vitro, mycophenolic acid inhibits tumor-associated angiogenesis and is used as clinical drug in immunosuppression
Mycophenolic acid
-
isozyme IMPDH II IC50: 11 nM, potent, uncompetitive inhibition, immunosuppressive drug, prodrug is mycophenolate mofetil
Mycophenolic acid
-
key binding interactions for the benzofuranone residue mycophenolic acid and the N-[3-methoxy-4-(5-oxazolyl)phenyl] fragment of VX-497, the benzofuranone ring mycophenolic acid binds in a spatially restricted region of the NAD+ binding site packing with the hypoxanthine ring xanthosine 5'-phosphate, the carbonyl oxygen and hydroxy residues are involved in a hydrogen bond array that involves Gly326, Thr333 and Gln441, the appending methyl substituent of the benzofuranone system, resides in a small hydrophobic pocket defined by the planes of Asn303 amide and Arg322 guanidine, the phenyl oxazole moiety of VX-497 binds in the same region as the benzofuranone ring of mycophenolic acid, forming hydrogen bonds between the oxazole nitrogen and oxygen with Gly326 and possibly Thr333, respectively, the methoxy residue binds in the same pocket as the benzofuranone methyl in mycophenolic acid
Mycophenolic acid
-
potent, uncompetitive, reversible, inhibits both isozymes, prodrug is mycophenolate mofetil
Mycophenolic acid
-
potent, uncompetitive, reversible, inhibits both isozymes, prodrug is mycophenolate mofetil, isozyme IMPDH II IC50: 14 nM
Mycophenolic acid
-
traps the reaction intermediate E-XMP, the human enzyme is sensitive to the inhibitor due to its open dehydrogenase conformation
Mycophenolic acid
-
uncompetitive inhibition, the interaction with the enzyme, inducing striking conformational changes and aggregation, is regulated by GTP, GTP reverses the enzyme aggregation by inhibitor mycophenolic acid, the inhibitor is part of an immunosuppressive drug
Mycophenolic acid
-
biphasic concentration-dependent influence on inosine 5'-phosphate dehydrogenase basal activity. At concentrations around or below IC50 value, mycophenolic acid increases the basal enzymic activity, associated with elevated expression of isoform IMPDH2. Despite increased expression, the basal enzyme activity decreases following exposure to high mycophenolic acid concentrations
Mycophenolic acid
-
comparison with inhibition of histone deacetylase and K562 cell proliferation
Mycophenolic acid
-
IMPDH activity in erythrocytes is inhibited at the peak plasma concentration of mycophenolic acid in initial kidney transplant recipients. Reduction does not coincide with the peak of the plasma concentration of phenolic and acyl glucuronides of mycophenolic acid
Mycophenolic acid
is a uncompetitive inhibitor of IMPDH with respect to both inosine 5'-phosphate and NAD+, inhibits IMPDH by trapping the covalent intermediate. It it is easily converted to mycophenolic acid-7-O-glucuronide, which limits the inhibitory efficacy and higher doses are therefore needed in order to maintain appropriate therapeutic levels
Mycophenolic acid
-
new enzymatic mycophenolic acid assay, cross-reactivity by mycophenolic acid-acyl-glucuronide is less than 5%, thus interference is expected to be clinically irrelevant
Mycophenolic acid
inhibition of leukemia K562 cells proliferation, IC50 of 7.7 microM
Mycophenolic acid
a natural product and a reversible, potent and uncompetitive inhibitor of IMPDH
Mycophenolic acid
reversible, potent, uncompetitive inhibitor, 99.9% inhibition at 0.01 mM
mycophenolic acid-acyl-glucuronide
-
cross-reactivity by mycophenolic acid is less than 5%, thus interference is expected to be clinically irrelevant
mycophenolic acid-acyl-glucuronide
-
uncompetitive inhibition, is a weaker inhibitor of IMPDH II than mycophenolic acid. When coincubated with mycophenolic acid, mycophenolic acid-acyl-glucuronide activity is negligible at pharmacological concentrations
NAD+
-
at high concentration, inhibition of canonical isoform. No inhibition of retinal-specific isoforms
P1-[7-hydroxy-6-(hydroxyethyl)-5-methoxy-4-methylphthtalan-1-one-2-yl]-P2-(2-ethyladenosin-5'-yl)methylenebis(phosphonate)
-
-
P1-[7-hydroxy-6-(hydroxyethyl)-5-methoxy-4-methylphthtalan-1-one-2-yl]-P2-(2-ethyladenosin-5'-yl)methylenebis(phosphonate)
-
ribavirin
1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide, a prodrug of corresponding 5-monophosphate, which as a competitive inhibitor interacts with the IMP domain of IMPDH
thiazole-4-carboxamide adenine dinucleotide
-
i.e. TAD, mixed inhibition type versus inosine 5'-phosphate and NAD+
thiazole-4-carboxamide adenine dinucleotide
-
i.e. TAD, synthesis, noncompetitive inhibition, conformational analysis, and biological activity of inhibitor analogues, overview, TAD binds to the NAD+ binding site with out isozyme specificity, mechanism and molecular modeling using the enzyme crystal structure, overview, cytotoxic against K562 tumor cells
thiazole-4-carboxamide adenine dinucleotide
inhibition of leukemia K562 cells proliferation, IC50 of 3.7 microM
tiazofurin
-
i.e. 2-beta-D-ribofuranosyl-thiazole-4-carboxamide, overview: clinical and molecular impact of inhibition
tiazofurin
-
the drug is tested in clinical use to treat acute myelocytic leukemia, AML, detailed overview, tiazofurin treatment may result in induced differentiation of leukemic leukocytes in patients, incubation of K-562 cells with tiazofurin produces inhibition of IMP DH and decreases GTP concentration, these biochemical alterations are followed by a decrease in the expression of as proto-oncogene which is followed by induced differentiation of these cells, biochemical mechanism, overview
VX-497
-
key binding interactions for the benzofuranone residue mycophenolic acid and the N-[3-methoxy-4-(5-oxazolyl)phenyl] fragment of VX-497, the benzofuranone ring mycophenolic acid binds in a spatially restricted region of the NAD+ binding site packing with the hypoxanthine ring xanthosine 5'-phosphate, the carbonyl oxygen and hydroxy residues are involved in a hydrogen bond array that involves Gly326, Thr333 and Gln441, the appending methyl substituent of the benzofuranone system, resides in a small hydrophobic pocket defined by the planes of Asn303 amide and Arg322 guanidine, the phenyl oxazole moiety of VX-497 binds in the same region as the benzofuranone ring of mycophenolic acid, forming hydrogen bonds between the oxazole nitrogen and oxygen with Gly326 and possibly Thr333, respectively, the methoxy residue binds in the same pocket as the benzofuranone methyl in mycophenolic acid
xanthosine 5'-phosphate
-
competitive versus inosine 5'-phosphate but noncompetitive versus NAD+
additional information
synthesis of mycophenolic acid derivatives as inhibitors. Functional groups at C5, C7, and C6' positions in mycophenolic acid are important for inhibitory activity against IMPDH. It is difficult to improve specificity against IMPDH II by modification of 5-, 7-, and 6'-group. Demethylation of 5-OMe results in increasing hydrophilicity, and lowering cell permeability. Ester bonds of protective groups at C7 and C6' positions are hydrolyzed to give mycophenolic acid in cultures, the effects of a tubulin-specific histone deacetylase inhibitor on proliferation and differentiation are weaker than its inhibitory activity against IMPDH
-
additional information
synthesis of mycophenolic acid derivatives as inhibitors. Functional groups at C5, C7, and C6' positions in mycophenolic acid are important for inhibitory activity against IMPDH. It is difficult to improve specificity against IMPDH II by modification of 5-, 7-, and 6'-group. Demethylation of 5-OMe results in increasing hydrophilicity, and lowering cell permeability. Ester bonds of protective groups at C7 and C6' positions are hydrolyzed to give mycophenolic acid in cultures, the effects of a tubulin-specific histone deacetylase inhibitor on proliferation and differentiation are weaker than its inhibitory activity against IMPDH
-
additional information
inhibitor synthesis, analysis and comparison of potencies against isozymes IMPDH1 and IMPDH2, overview
-
additional information
inhibitor synthesis, analysis and comparison of potencies against isozymes IMPDH1 and IMPDH2, overview
-
additional information
-
6-ethoxycarbonyl-3,3-disubstituted-1,5-diazabicyclo[3.1.0.]hexane-2,4-diones inhibit type II enzyme
-
additional information
-
determination and analysis of structure-activity relationships of the different inhibitor molecules, overview
-
additional information
-
development and synthesis of inhibitors, determination and analysis of structure-activity relationships of the different inhibitor molecules with isozyme IMPDH II, overview
-
additional information
-
inhibition of the enzyme in K562 cells sensitizes the before resistant cells to methotrexate
-
additional information
-
optimization of nitrile containing drugs, such as VX-148, by combining them with an oxazole moiety which is very reactive in inhibition, overview
-
additional information
-
synthesis, inhibitory potency, and structure-activity relationship of enzyme with phosphonic acid-containing analogues of mycophenolic acid inhibitors, IC50 values, overview
-
additional information
-
the enzyme is resistant to mizoribine 5'-phosphate due to its open dehydrogenase conformation in opposite to the bacterial enzyme which has a closed hydrolase conformation
-
additional information
-
retinal isoforms do not bind significant fractions of a random pool of oligonucleotides
-
additional information
-
IMPDH activity decreases more than 10% with increasing contamination by erythrocytes due to increasing AMP and protein content. Storage of lithium heparin blood samples at room temperature for 24 hours before peripheral blood mononuclear cell isolation does not lead to any significant changes in the IMPDH activity, when the activity is normalized to the AMP concentration
-
additional information
IMPDH2 interacts with protein kinase B/Akt via its plekstrin homology domain, the resulting phosphorylation reduces activity
-
additional information
IMPDH2 interacts with protein kinase B/Akt via its plekstrin homology domain, the resulting phosphorylation reduces activity
-
additional information
involvement of three conserved water molecules (W(L), W(M), and W(C)) in the recognition of catalytic residues (R 322, D 364, and N 303) to inhibitor
-
additional information
-
involvement of three conserved water molecules (W(L), W(M), and W(C)) in the recognition of catalytic residues (R 322, D 364, and N 303) to inhibitor
-
additional information
synthesis of mycophenolic acid derivatives as inhibitors. Functional groups at C5, C7, and C6' positions in mycophenolic acid are important for inhibitory activity against IMPDH. It is difficult to improve specificity against IMPDH II by modification of 5-, 7-, and 6'-group. Demethylation of 5-OMe results in increasing hydrophilicity, and lowering cell permeability. Ester bonds of protective groups at C7 and C6' positions are hydrolyzed to give mycophenolic acid in cultures, the effects of a tubulin-specific histone deacetylase inhibitor on proliferation and differentiation are weaker than its inhibitory activity against IMPDH
-
additional information
synthesis of mycophenolic acid derivatives as inhibitors. Functional groups at C5, C7, and C6' positions in mycophenolic acid are important for inhibitory activity against IMPDH. It is difficult to improve specificity against IMPDH II by modification of 5-, 7-, and 6'-group. Demethylation of 5-OMe results in increasing hydrophilicity, and lowering cell permeability. Ester bonds of protective groups at C7 and C6' positions are hydrolyzed to give mycophenolic acid in cultures, the effects of a tubulin-specific histone deacetylase inhibitor on proliferation and differentiation are weaker than its inhibitory activity against IMPDH
-
additional information
-
tacrolimus, cyclosporine and prednisolone do not affect IMPDH activity
-
additional information
inhibitor synthesis, analysis and comparison of potencies against isozymes IMPDH1 and IMPDH2, overview
-
additional information
inhibitor synthesis, analysis and comparison of potencies against isozymes IMPDH1 and IMPDH2, overview
-
additional information
structure- and ligand-based IMPDH inhibitor development, molecular modeling studies, overview
-
additional information
-
structure- and ligand-based IMPDH inhibitor development, molecular modeling studies, overview
-
additional information
enzyme cytoophidia are catalytically active and resistant to GDP allosteric inhibition
-
additional information
-
enzyme cytoophidia are catalytically active and resistant to GDP allosteric inhibition
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
mycophenolate mofetil
-
median IMPDH activity in erythrocytes is 1.73times higher in mycophenolate mofetil positive than in mycophenolate mofetil negative kidney transplant recipients. Predose IMPDH activity in erythrocytes is induced slowly by mycophenolate mofetil therapy and is dependent on mycophenolic acid, phenolic and acyl glucuronides in stable kidney transplant recipients
additional information
ATP shows no significant effect on the catalytic activity of the enzyme
-
additional information
-
ATP shows no significant effect on the catalytic activity of the enzyme
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
ssDNA binding kinetics of wild-type and mutant IMPDH1s
-
additional information
additional information
-
wild type and mutants of type II
-
additional information
additional information
-
nucleic acid binding kinetics, recombinant full-length type I isozyme and subdomain
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000077
6-((E)-4-(((1-(50-deoxy-adenosin-50-yl)-1H-1,2,3-triazol-4-yl)-methyl)amino)-3-methylbut-2-en-1-yl)-7-hydroxy-5-methoxy-4-methylisobenzofuran-1(3H)-one
pH 8.0, 25°C
0.00007
6-((E)-4-(4-(adenosin-50-yl)methyl-1H-1,2,3-triazol-1-yl)-3-methylbut-2-en-1-yl)-7-hydroxy-5-methoxy-4-methylisobenzofuran-1(3H)-one
pH 8.0, 25°C
0.00055
(2E)-N-(4-chlorophenyl)-4-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)but-2-enamide
at pH 8.0 and 25°C
0.0004
(4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methyl-N-[4-(trifluoromethyl)phenyl]hex-4-enamide
at pH 8.0 and 25°C
0.00034
(4E)-N-(3,4-dichlorophenyl)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
at pH 8.0 and 25°C
0.00035
(4E)-N-(4-chloro-3-methoxyphenyl)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
at pH 8.0 and 25°C
0.00013
(4E)-N-(4-chlorophenyl)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
at pH 8.0 and 25°C
0.00035
(4E)-N-(4-cyanophenyl)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
at pH 8.0 and 25°C
0.00027
(4E)-N-(4-fluorophenyl)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
at pH 8.0 and 25°C
0.00023
(4E)-N-[4-chloro-3-(trifluoromethyl)phenyl]-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
at pH 8.0 and 25°C
0.0004 - 0.0011
(5E)-N-hydroxy-7-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-5-methylhept-5-enamide
0.00087
3-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)propyl (4-chlorophenyl)carbamate
at pH 8.0 and 25°C
0.000034
6-((E)-4-(((1-(50-deoxy-adenosin-50-yl)-1H-1,2,3-triazol-4-yl)-methyl)amino)-3-methylbut-2-en-1-yl)-7-hydroxy-5-methoxy-4-methylisobenzofuran-1(3H)-one
pH 8.0, 25°C
0.000044
6-((E)-4-(4-(adenosin-50-yl)methyl-1H-1,2,3-triazol-1-yl)-3-methylbut-2-en-1-yl)-7-hydroxy-5-methoxy-4-methylisobenzofuran-1(3H)-one
pH 8.0, 25°C
0.44 - 0.82
9-(5-deoxy-5-([(([2-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)ethoxy]sulfonyl)methyl)sulfonyl]amino)-b-L-ribofuranosyl)-2-ethyl-9H-purin-6-amine
0.18 - 0.52
9-(5-deoxy-5-([(([2-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)ethoxy]sulfonyl)methyl)sulfonyl]amino)-b-L-ribofuranosyl)-2-ethynyl-9H-purin-6-amine
0.31 - 0.66
9-(5-deoxy-5-([(([2-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)ethoxy]sulfonyl)methyl)sulfonyl]amino)-b-L-ribofuranosyl)-2-phenyl-9H-purin-6-amine
0.17 - 0.35
9-(5-deoxy-5-([(([2-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)ethoxy]sulfonyl)methyl)sulfonyl]amino)-b-L-ribofuranosyl)-9H-purin-6-amine
0.0008
N-(4-chlorophenyl)-2-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)acetamide
at pH 8.0 and 25°C
0.00029
N-(4-chlorophenyl)-4-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)butanamide
at pH 8.0 and 25°C
0.00046
N-[4-chloro-3-(trifluoromethyl)phenyl]-3-[(1R,2S)-2-[(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)methyl]-1-methylcyclopropyl]propanamide
at pH 8.0 and 25°C
0.0014
N-[4-chloro-3-(trifluoromethyl)phenyl]-3-[(1S,2R)-2-[(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)methyl]-1-methylcyclopropyl]propanamide
at pH 8.0 and 25°C
0.02 - 0.037
P1-(7-hydroxy-6-(ethyl-2-yl)-5-methoxy-4-methylphthalan-1-one)methylenephospho-P2-(adenosin-5'-yl)phosphonate
-
pH 8.0, 25°C
0.06 - 0.087
P1-(adenosine-5'-yl)methylenephospho-P2-(7-hydroxy-6-(ethyl-2-yl)-5-methoxy-4-methylphthalan-1-one)phosphonate
-
pH 8.0, 25°C
0.000095 - 0.00014
P1-(thiazofurin-5'-yl)-P2-(adenosyl-5'-yl)-alpha,beta-methylene diphosphate
0.02 - 0.04
P1-[7-hydroxy-6-(hydroxyethyl)-5-methoxy-4-methylphthtalan-1-one-2-yl]-P2-(2-ethyladenosin-5'-yl)methylenebis(phosphonate)
0.07 - 0.11
P1-[7-hydroxy-6-(hydroxyethyl)-5-methoxy-4-methylphthtalan-1-one-2-yl]-P2-(2-phenyladenosin-5'-yl)methylenebis(phosphonate)
0.25 - 0.33
P1-[7-hydroxy-6-(hydroxyethyl)-5-methoxy-4-methylphthtalan-1-one-2-yl]-P2-(adenosin-5'-yl)methylenebis(phosphonate)
0.0004
(5E)-N-hydroxy-7-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-5-methylhept-5-enamide
-
isoform IMPDH1, pH 8.0, 25°C
0.0011
(5E)-N-hydroxy-7-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-5-methylhept-5-enamide
-
isoform IMPDH2, pH 8.0, 25°C
0.44
9-(5-deoxy-5-([(([2-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)ethoxy]sulfonyl)methyl)sulfonyl]amino)-b-L-ribofuranosyl)-2-ethyl-9H-purin-6-amine
isoform IMPDH2, pH 8.0, 25°C
0.82
9-(5-deoxy-5-([(([2-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)ethoxy]sulfonyl)methyl)sulfonyl]amino)-b-L-ribofuranosyl)-2-ethyl-9H-purin-6-amine
isoform IMPDH1, pH 8.0, 25°C
0.18
9-(5-deoxy-5-([(([2-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)ethoxy]sulfonyl)methyl)sulfonyl]amino)-b-L-ribofuranosyl)-2-ethynyl-9H-purin-6-amine
isoform IMPDH2, pH 8.0, 25°C
0.52
9-(5-deoxy-5-([(([2-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)ethoxy]sulfonyl)methyl)sulfonyl]amino)-b-L-ribofuranosyl)-2-ethynyl-9H-purin-6-amine
isoform IMPDH1, pH 8.0, 25°C
0.31
9-(5-deoxy-5-([(([2-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)ethoxy]sulfonyl)methyl)sulfonyl]amino)-b-L-ribofuranosyl)-2-phenyl-9H-purin-6-amine
isoform IMPDH2, pH 8.0, 25°C
0.66
9-(5-deoxy-5-([(([2-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)ethoxy]sulfonyl)methyl)sulfonyl]amino)-b-L-ribofuranosyl)-2-phenyl-9H-purin-6-amine
isoform IMPDH1, pH 8.0, 25°C
0.17
9-(5-deoxy-5-([(([2-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)ethoxy]sulfonyl)methyl)sulfonyl]amino)-b-L-ribofuranosyl)-9H-purin-6-amine
isoform IMPDH2, pH 8.0, 25°C
0.35
9-(5-deoxy-5-([(([2-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)ethoxy]sulfonyl)methyl)sulfonyl]amino)-b-L-ribofuranosyl)-9H-purin-6-amine
isoform IMPDH1, pH 8.0, 25°C
0.000511
mycophenolic acid-acyl-glucuronide
-
in the presence of inosine 5'-phosphate
0.0017
N-hydroxy-N'-[3-methoxy-4-(1,3-oxazol-2-yl)phenyl]octanediamide
-
isoform IMPDH2, pH 8.0, 25°C
0.005
N-hydroxy-N'-[3-methoxy-4-(1,3-oxazol-2-yl)phenyl]octanediamide
-
isoform IMPDH1, pH 8.0, 25°C
0.000095
P1-(thiazofurin-5'-yl)-P2-(adenosyl-5'-yl)-alpha,beta-methylene diphosphate
-
type 1 isozyme
0.00014
P1-(thiazofurin-5'-yl)-P2-(adenosyl-5'-yl)-alpha,beta-methylene diphosphate
-
type 2 isozyme
0.000007
P1-(tiazofurin-5'-yl)-P2-(2-aminoadenosin-5'-yl) diphosphate
-
isoform IMPDH1, pH 8.0, 25°C
0.000027
P1-(tiazofurin-5'-yl)-P2-(2-aminoadenosin-5'-yl) diphosphate
-
isoform IMPDH2, pH 8.0, 25°C
0.000001
P1-(tiazofurin-5'-yl)-P2-(2-ethyladenosin-5'-yl) diphosphate
-
isoform IMPDH1, pH 8.0, 25°C
0.000014
P1-(tiazofurin-5'-yl)-P2-(2-ethyladenosin-5'-yl) diphosphate
-
isoform IMPDH2, pH 8.0, 25°C
0.00001
P1-(tiazofurin-5'-yl)-P2-(2-ethynyladenosin-5'-yl) diphosphate
-
isoform IMPDH1, pH 8.0, 25°C
0.000049
P1-(tiazofurin-5'-yl)-P2-(2-ethynyladenosin-5'-yl) diphosphate
-
isoform IMPDH2, pH 8.0, 25°C
0.000019
P1-(tiazofurin-5'-yl)-P2-(2-iodoadenosin-5'-yl) diphosphate
-
isoform IMPDH1, pH 8.0, 25°C
0.000084
P1-(tiazofurin-5'-yl)-P2-(2-iodoadenosin-5'-yl) diphosphate
-
isoform IMPDH2, pH 8.0, 25°C
0.00002
P1-(tiazofurin-5'-yl)-P2-(2-phenyladenosin-5'-yl) diphosphate
-
isoform IMPDH1, pH 8.0, 25°C
0.000143
P1-(tiazofurin-5'-yl)-P2-(2-phenyladenosin-5'-yl) diphosphate
-
isoform IMPDH2, pH 8.0, 25°C
0.00011
P1-(tiazofurin-5'-yl)-P2-(adenosin-5'-yl) diphosphate
-
isoform IMPDH1, pH 8.0, 25°C
0.00011
P1-(tiazofurin-5'-yl)-P2-(adenosin-5'-yl) diphosphate
-
isoform IMPDH2, pH 8.0, 25°C
0.02
P1-[7-hydroxy-6-(hydroxyethyl)-5-methoxy-4-methylphthtalan-1-one-2-yl]-P2-(2-ethyladenosin-5'-yl)methylenebis(phosphonate)
isoform IMPDH1, pH 8.0, 25°C
0.04
P1-[7-hydroxy-6-(hydroxyethyl)-5-methoxy-4-methylphthtalan-1-one-2-yl]-P2-(2-ethyladenosin-5'-yl)methylenebis(phosphonate)
-
isoform IMPDH2, pH 8.0, 25°C
0.04
P1-[7-hydroxy-6-(hydroxyethyl)-5-methoxy-4-methylphthtalan-1-one-2-yl]-P2-(2-ethyladenosin-5'-yl)methylenebis(phosphonate)
isoform IMPDH2, pH 8.0, 25°C
0.07
P1-[7-hydroxy-6-(hydroxyethyl)-5-methoxy-4-methylphthtalan-1-one-2-yl]-P2-(2-phenyladenosin-5'-yl)methylenebis(phosphonate)
isoform IMPDH1, pH 8.0, 25°C
0.11
P1-[7-hydroxy-6-(hydroxyethyl)-5-methoxy-4-methylphthtalan-1-one-2-yl]-P2-(2-phenyladenosin-5'-yl)methylenebis(phosphonate)
isoform IMPDH2, pH 8.0, 25°C
0.25
P1-[7-hydroxy-6-(hydroxyethyl)-5-methoxy-4-methylphthtalan-1-one-2-yl]-P2-(adenosin-5'-yl)methylenebis(phosphonate)
isoform IMPDH2, pH 8.0, 25°C
0.33
P1-[7-hydroxy-6-(hydroxyethyl)-5-methoxy-4-methylphthtalan-1-one-2-yl]-P2-(adenosin-5'-yl)methylenebis(phosphonate)
isoform IMPDH1, pH 8.0, 25°C
0.00029
thiazole-4-carboxamide adenine dinucleotide
-
versus inosine 5'-phosphate
additional information
additional information
-
inhibition patterns, isozymes I and II
-
additional information
additional information
-
mycophenolic acid inhibition kinetics
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00015
(4E)-6-(4,6-dihydroxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enoic acid
Homo sapiens
pH 7.4, 37°C
0.0041
(4E)-6-[4-(acetyloxy)-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl]-4-methylhex-4-enoic acid
Homo sapiens
pH 7.4, 37°C
0.00035
(4E)-N-hydroxy-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
Homo sapiens
pH 7.4, 37°C
0.00002
14,16-dihydroxy-3,8-dimethyl-3,4,5,6,9,10-hexahydro-1H-2-benzoxacyclotetradecine-1,7(8H)-dione
Homo sapiens
pH 8.0, 25°C
0.000099
2-ethyl-9-[5-O-[hydroxy(2-[hydroxy[2-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)ethoxy]phosphoryl]ethyl)phosphoryl]-beta-L-ribofuranosyl]-9H-purin-6-amine
Homo sapiens
pH 8.0, 25°C
0.0015
methyl (4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enoate
Homo sapiens
pH 7.4, 37°C
0.000005
mycophenolic 2-ethyladenosin-5'-yl-difluoromethylenebis(phosphonate)
Homo sapiens
pH 8.0, 25°C
0.000016
mycophenolic 2-ethyladenosin-5'-yl-methylenebis(phosphonate)
Homo sapiens
pH 8.0, 25°C
0.000013
thiazofurin-5'-yl-2-ethyladenosin-5'-yl-difluromethylene bis(phosphonate)
Homo sapiens
pH 8.0, 25°C
0.000001
thiazole-4-carboxamide 2-ethyladenine dinucleotide
Homo sapiens
pH 8.0, 25°C
0.000785
(2-[acetyl[(2E)-4-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-2-methylbut-2-en-1-yl]amino]ethyl)phosphonic acid
Homo sapiens
-
isozyme IMPDH II IC50: 785 nM
0.000749
(2-[formyl[(2E)-4-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-2-methylbut-2-en-1-yl]amino]ethyl)phosphonic acid
Homo sapiens
-
isozyme IMPDH II IC50: 749 nM
0.001
(2-[[(2E)-4-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-2-methylbut-2-en-1-yl](methyl)amino]ethyl)phosphonic acid
Homo sapiens
-
isozyme IMPDH II IC50: above 0.001 mM
0.000498
(2-[[(2E)-4-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-2-methylbut-2-en-1-yl](methylsulfonyl)amino]ethyl)phosphonic acid
Homo sapiens
-
isozyme IMPDH II IC50: 498 nM
0.000093
(2-[[(2E)-4-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-2-methylbut-2-en-1-yl](sulfamoyl)amino]ethyl)phosphonic acid
Homo sapiens
-
isozyme IMPDH II IC50: 93 nM
0.000499
(2-[[(2E)-4-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-2-methylbut-2-en-1-yl]amino]ethyl)phosphonic acid
Homo sapiens
-
isozyme IMPDH II IC50: 499 nM
0.000132
(2-[[(2E)-4-(6-ethyl-4-hydroxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-2-methylbut-2-en-1-yl](methyl)amino]ethyl)phosphonic acid
Homo sapiens
-
isozyme IMPDH II IC50: 132 nM
0.000068
(2-[[(2E)-4-(6-ethyl-4-hydroxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-2-methylbut-2-en-1-yl](methylsulfonyl)amino]ethyl)phosphonic acid
Homo sapiens
-
isozyme IMPDH II IC50: 68 nM
0.000024
(2-[[(2E)-4-(6-ethyl-4-hydroxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-2-methylbut-2-en-1-yl](sulfamoyl)amino]ethyl)phosphonic acid
Homo sapiens
-
isozyme IMPDH II IC50: 24 nM
0.000013
(2-[[(2E)-4-(6-ethyl-4-hydroxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-2-methylbut-2-en-1-yl]amino]ethyl)phosphonic acid
Homo sapiens
-
isozyme IMPDH II IC50: 13 nM
0.002
(2E)-3-furan-2-yl-N-[4-(4-methyl-1,3-oxazol-5-yl)phenyl]prop-2-enamide
Homo sapiens
-
isozyme IMPDH II IC50: 0.002 mM
0.00017
(4E)-6-(4,6-dihydroxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enoic acid
Homo sapiens
pH 7.4, 37°C
0.00082
(4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methyl-N-[(2R)-2-phenylpropyl]hex-4-enamide
Homo sapiens
isoform IMPDH2, at pH 8.6 and 37°C
0.0005
(4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methyl-N-[2-(2-methylphenyl)ethyl]hex-4-enamide
Homo sapiens
isoform IMPDH2, at pH 8.6 and 37°C
0.0006
(4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methyl-N-[2-(4-methylphenyl)ethyl]hex-4-enamide
Homo sapiens
isoform IMPDH2, at pH 8.6 and 37°C
0.00033
(4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-N-[2-(4-methoxyphenyl)ethyl]-4-methylhex-4-enamide
Homo sapiens
isoform IMPDH2, at pH 8.6 and 37°C
0.0041
(4E)-6-[4-(acetyloxy)-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl]-4-methylhex-4-enoic acid
Homo sapiens
pH 7.4, 37°C
0.00042
(4E)-N-hydroxy-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
Homo sapiens
pH 7.4, 37°C
0.00048
(4E)-N-[(4-butylphenyl)methyl]-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
Homo sapiens
isoform IMPDH2, at pH 8.6 and 37°C
0.00073
(4E)-N-[2-(2-chlorophenyl)ethyl]-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
Homo sapiens
isoform IMPDH2, at pH 8.6 and 37°C
0.00051
(4E)-N-[2-(2H-1,3-benzodioxol-5-yl)ethyl]-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
Homo sapiens
isoform IMPDH2, at pH 8.6 and 37°C
0.00057
(4E)-N-[2-(4-chlorophenyl)ethyl]-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enamide
Homo sapiens
isoform IMPDH2, at pH 8.6 and 37°C
0.000246
([[(2E)-4-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-2-methylbut-2-en-1-yl]oxy]methyl)phosphonic acid
Homo sapiens
-
isozyme IMPDH II IC50: 246 nM
0.000023
([[(2E)-4-(6-ethyl-4-hydroxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-2-methylbut-2-en-1-yl]oxy]methyl)phosphonic acid
Homo sapiens
-
isozyme IMPDH II IC50: 23 nM
0.094
1-(2,2-dimethylpropanoyl)-7'-methoxy-3'-methyl-6'-(1,3-oxazol-5-yl)-1'H-spiro[pyrrolidine-3,2'-quinazolin]-4'(3'H)-one
Homo sapiens
-
IC50: 0.094 mM, isozyme IMPDH II
0.00064
1-(3-methylphenyl)-3-[4-(1,3-oxazol-5-yl)phenyl]urea
Homo sapiens
-
isozyme IMPDH II IC50: 640 nM
0.000033
1-methyl-6-[(5-phenyl-1,3-oxazol-2-yl)amino]-1H-indole-3-carbonitrile
Homo sapiens
-
0.000035
1-tert-butyl 5-methyl (3R,5R)-7'-methoxy-3'-methyl-6'-(1,3-oxazol-5-yl)-4'-oxo-3',4'-dihydro-1H,1'H-spiro[pyrrolidine-3,2'-quinazoline]-1,5-dicarboxylate
Homo sapiens
-
IC50: 35 nM, isozyme IMPDH II
0.000948
1-tert-butyl 5-methyl (3R,5S)-7'-methoxy-3'-methyl-6'-(1,3-oxazol-5-yl)-4'-oxo-3',4'-dihydro-1H,1'H-spiro[pyrrolidine-3,2'-quinazoline]-1,5-dicarboxylate
Homo sapiens
-
IC50: 948 nM, isozyme IMPDH II
0.000035
1-tert-butyl 5-methyl (3S,5R)-7'-methoxy-3'-methyl-6'-(1,3-oxazol-5-yl)-4'-oxo-3',4'-dihydro-1H,1'H-spiro[pyrrolidine-3,2'-quinazoline]-1,5-dicarboxylate
Homo sapiens
-
IC50: 35 nM, isozyme IMPDH II
0.000043
1-[3-chloro-4-(1,3-oxazol-5-yl)phenyl]-3-(3-methylphenyl)urea
Homo sapiens
-
isozyme IMPDH II IC50: 43 nM
0.000019
1-[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]-3-(3-methylphenyl)urea
Homo sapiens
-
isozyme IMPDH II IC50: 19 nM
0.0005
1-[4-(4-methyl-1,3-oxazol-5-yl)phenyl]-3-(3-methylphenyl)urea
Homo sapiens
-
isozyme IMPDH II IC50: 500 nM
0.0016
2-(1,3-oxazol-5-yl)-5-[(5-phenyl-1,3-oxazol-2-yl)amino]phenol
Homo sapiens
-
isozyme IMPDH II IC50: 0.0016 mM
0.00003
2-(1-benzothiophen-3-yl)-6-methoxy-5-(1,3-oxazol-5-yl)-1H-indole-3-carbaldehyde
Homo sapiens
-
0.0002
2-(dimethylamino)-7-methoxy-6-(1,3-oxazol-5-yl)quinolin-4(1H)-one
Homo sapiens
-
isozyme IMPDH II IC50: 200 nM
0.00018
2-benzyl-7-methoxy-6-(1,3-oxazol-5-yl)quinolin-4(1H)-one
Homo sapiens
-
isozyme IMPDH II IC50: 180 nM
0.00024
2-cyano-1-[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]-3-phenylguanidine
Homo sapiens
-
isozyme IMPDH II IC50: 240 nM
0.000073
2-ethyl-9-[5-O-[hydroxy(2-[hydroxy[2-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)ethoxy]phosphoryl]ethyl)phosphoryl]-beta-L-ribofuranosyl]-9H-purin-6-amine
Homo sapiens
pH 8.0, 25°C
0.000032
2-furan-3-yl-7-methoxy-6-(1,3-oxazol-5-yl)quinolin-4(1H)-one
Homo sapiens
-
isozyme IMPDH II IC50: 32 nM
0.000041
2-hydroxy-N-[2-(2-[[3-methoxy-4-(1,3-oxazol-4-yl)phenyl]amino]-1,3-oxazol-5-yl)phenyl]-N-methylacetamide
Homo sapiens
-
isozyme IMPDH II IC50: 41 nM
0.01
2-tert-butyl-7-methoxy-6-(1,3-oxazol-5-yl)quinolin-4(1H)-one
Homo sapiens
-
isozyme IMPDH II IC50: 0.01 mM
0.000007
2-[methyl[2-(2-[[3-(1,3-oxazol-5-yl)-1H-indol-6-yl]amino]-1,3-oxazol-5-yl)phenyl]amino]-2-oxoethyl acetate
Homo sapiens
-
0.000033 - 0.00042
3-cyanoindole-based inhibitors
Homo sapiens
-
synthesis and initial structureactivity relationships of 3-cyanoindole-based inhibitors with isozyme IMPDH II, IC50: 33-420 nM, comparison to other inhibitor structural classes, overview
-
0.0001
3-hydroxy-N-methyl-N-[2-(2-[[3-methyl-4-(1,3-oxazol-5-yl)phenyl]amino]-1,3-oxazol-5-yl)phenyl]propanamide
Homo sapiens
-
isozyme IMPDH II IC50: 100 nM
0.000021
3-hydroxy-N-[2-(2-[[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]amino]-1,3-oxazol-5-yl)phenyl]-N-methylpropanamide
Homo sapiens
-
isozyme IMPDH II IC50: 21 nM
0.000005 - 0.00016
3-phenyl quinolone derivatives
Homo sapiens
-
several, isozyme IMPDH II IC50: 5-160 nM, overview
-
0.000018
4-[[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]amino]-6-phenyl-1,3,5-triazin-2-ol
Homo sapiens
-
0.00076
5-chloro-1,4-dimethyl-2H-cyclopenta[d]pyridazine-6-carbonitrile
Homo sapiens
-
0.000328
7'-methoxy-3'-methyl-6'-(1,3-oxazol-5-yl)-1'H-spiro[cyclopentane-1,2'-quinazolin]-4'(3'H)-one
Homo sapiens
-
IC50: 328 nM, isozyme IMPDH II
0.068
7'-methoxy-3'-methyl-6'-(1,3-oxazol-5-yl)-1-(piperidin-1-ylcarbonyl)-1'H-spiro[pyrrolidine-3,2'-quinazolin]-4'(3'H)-one
Homo sapiens
-
IC50: 0.068 mM, isozyme IMPDH II
0.000526
7'-methoxy-3'-methyl-6'-(1,3-oxazol-5-yl)-2,3,5,6-tetrahydro-1'H-spiro[pyran-4,2'-quinazolin]-4'(3'H)-one
Homo sapiens
-
IC50: 526 nM, isozyme IMPDH II
0.393
7'-methoxy-3'-methyl-6'-(1,3-oxazol-5-yl)-4'-oxo-N-phenyl-3',4'-dihydro-1H,1'H-spiro[pyrrolidine-3,2'-quinazoline]-1-carboxamide
Homo sapiens
-
IC50: 0.393 mM, isozyme IMPDH II
0.000096
7'-methoxy-3'-methyl-6'-(1,3-oxazol-5-yl)-4,6-dihydro-1'H-spiro[cyclopenta[b]thiophene-5,2'-quinazolin]-4'(3'H)-one
Homo sapiens
-
IC50: 96 nM, isozyme IMPDH II
0.071
7'-methoxy-3'-methyl-N,N-bis(1-methylethyl)-6'-(1,3-oxazol-5-yl)-4'-oxo-3',4'-dihydro-1H,1'H-spiro[pyrrolidine-3,2'-quinazoline]-1-carboxamide
Homo sapiens
-
IC50: 0.071 mM, isozyme IMPDH II
0.064
7'-methoxy-N,3'-dimethyl-6'-(1,3-oxazol-5-yl)-4'-oxo-N-phenyl-3',4'-dihydro-1H,1'H-spiro[pyrrolidine-3,2'-quinazoline]-1-carboxamide
Homo sapiens
-
IC50: 0.064 mM, isozyme IMPDH II
0.000254
7-hydroxy-5-methoxy-4-methyl-6-(3-methylbut-2-en-1-yl)-2-benzofuran-1(3H)-one
Homo sapiens
-
isozyme IMPDH II IC50: 254 nM
0.000273
7-hydroxy-5-methoxy-6-[(2E)-4-methoxy-3-methylbut-2-en-1-yl]-4-methyl-2-benzofuran-1(3H)-one
Homo sapiens
-
isozyme IMPDH II IC50: 273 nM
0.000192
7-methoxy-2,2,3-trimethyl-6-(1,3-oxazol-5-yl)-2,3-dihydroquinazolin-4(1H)-one
Homo sapiens
-
IC50: 192 nM, isozyme IMPDH II
0.0003
7-methoxy-2,2-dimethyl-6-(1,3-oxazol-5-yl)-3-(2-pyridin-4-ylethyl)-2,3-dihydroquinazolin-4(1H)-one
Homo sapiens
-
IC50: 300 nM, isozyme IMPDH II
0.000049
7-methoxy-2,3-dimethyl-6-(1,3-oxazol-5-yl)-2-[(E)-2-phenylethenyl]-2,3-dihydroquinazolin-4(1H)-one
Homo sapiens
-
IC50: 49 nM, isozyme IMPDH II
0.000005
7-methoxy-2-(3-methylphenyl)-6-(1,3-oxazol-5-yl)quinolin-4(1H)-one
Homo sapiens
-
0.00022
7-methoxy-2-(methylamino)-6-(1,3-oxazol-5-yl)quinolin-4(1H)-one
Homo sapiens
-
isozyme IMPDH II IC50: 220 nM
0.00011
7-methoxy-2-methyl-6-(1,3-oxazol-5-yl)quinolin-4(1H)-one
Homo sapiens
-
isozyme IMPDH II IC50: 110 nM
0.000065
7-methoxy-3-methyl-6-(1,3-oxazol-5-yl)-2-phenylquinolin-4(1H)-one
Homo sapiens
-
isozyme IMPDH II IC50: 65 nM
0.000104
7-methoxy-3-methyl-6-(1,3-oxazol-5-yl)quinazoline-2,4(1H,3H)-dione
Homo sapiens
-
IC50: 104 nM, isozyme IMPDH II
0.00021
7-methoxy-6-(1,3-oxazol-4-yl)-2-phenylquinolin-4(1H)-one
Homo sapiens
-
isozyme IMPDH II IC50: 210 nM
0.000034
7-methoxy-6-(1,3-oxazol-5-yl)-2-(1,3-thiazol-4-yl)quinolin-4(1H)-one
Homo sapiens
-
isozyme IMPDH II IC50: 34 nM
0.000008
7-methoxy-6-(1,3-oxazol-5-yl)-2-phenoxyquinolin-4(1H)-one
Homo sapiens
-
isozyme IMPDH II IC50: 8 nM
0.000008
7-methoxy-6-(1,3-oxazol-5-yl)-2-phenylquinolin-4(1H)-one
Homo sapiens
-
isozyme IMPDH II IC50: 8 nM
0.000043
7-methoxy-6-(1,3-oxazol-5-yl)-2-pyridin-2-ylquinolin-4(1H)-one
Homo sapiens
-
isozyme IMPDH II IC50: 43 nM
0.00007
7-methoxy-6-(1,3-oxazol-5-yl)-2-pyridin-3-ylquinolin-4(1H)-one
Homo sapiens
-
isozyme IMPDH II IC50: 70 nM
0.000046
7-methoxy-6-(1,3-oxazol-5-yl)-2-pyridin-4-ylquinolin-4(1H)-one
Homo sapiens
-
isozyme IMPDH II IC50: 46 nM
0.000063
7-methoxy-6-(1,3-oxazol-5-yl)-2-thiophen-2-ylquinolin-4(1H)-one
Homo sapiens
-
isozyme IMPDH II IC50: 63 nM
0.000009
7-methoxy-6-(1,3-oxazol-5-yl)-2-thiophen-3-ylquinolin-4(1H)-one
Homo sapiens
-
isozyme IMPDH II IC50: 9 nM
0.000303
7-methoxy-6-(1,3-oxazol-5-yl)-2-thioxo-2,3-dihydroquinazolin-4(1H)-one
Homo sapiens
-
IC50: 303 nM
0.000013
7-methoxy-6-(1,3-oxazol-5-yl)-3-(2-pyridin-4-ylethyl)-2-thioxo-2,3-dihydroquinazolin-4(1H)-one
Homo sapiens
-
0.0003
7-methoxy-6-(1,3-oxazol-5-yl)quinolin-4(1H)-one
Homo sapiens
-
isozyme IMPDH II IC50: 300 nM
0.000037
9-(5-O-[hydroxy[([hydroxy[2-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)ethoxy]phosphoryl]oxy)methyl]phosphoryl]-beta-L-ribofuranosyl)-9H-purin-6-amine
Homo sapiens
pH 8.0, 25°C
0.001
dimethyl (2-[[(2E)-4-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-2-methylbut-2-en-1-yl]amino]ethyl)phosphonate
Homo sapiens
-
isozyme IMPDH II IC50: above 0.001 mM
0.000289
dimethyl [(2E)-4-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-2-methylbut-2-en-1-yl]phosphonate
Homo sapiens
-
isozyme IMPDH II IC50: 289 nM
0.08
ethyl 7'-methoxy-3'-methyl-6'-(1,3-oxazol-5-yl)-4'-oxo-3',4'-dihydro-1H,1'H-spiro[pyrrolidine-3,2'-quinazoline]-1-carboxylate
Homo sapiens
-
IC50: 0.08 mM, isozyme IMPDH II
0.0014
methyl (4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enoate
Homo sapiens
pH 7.4, 37°C
0.000024
mycophenolic 2-ethyladenosin-5'-yl-difluoromethylenebis(phosphonate)
Homo sapiens
pH 8.0, 25°C
0.000038
mycophenolic 2-ethyladenosin-5'-yl-methylenebis(phosphonate)
Homo sapiens
pH 8.0, 25°C
0.079
N,7'-dimethoxy-N,3'-dimethyl-6'-(1,3-oxazol-5-yl)-4'-oxo-3',4'-dihydro-1H,1'H-spiro[pyrrolidine-3,2'-quinazoline]-1-carboxamide
Homo sapiens
-
IC50: 0.079 mM, isozyme IMPDH II
0.045
N,N-diethyl-7'-methoxy-3'-methyl-6'-(1,3-oxazol-5-yl)-4'-oxo-3',4'-dihydro-1H,1'H-spiro[pyrrolidine-3,2'-quinazoline]-1-carboxamide
Homo sapiens
-
IC50: 0.045 mM, isozyme IMPDH II
0.051
N-(2,4-difluorophenyl)-7'-methoxy-N,3'-dimethyl-6'-(1,3-oxazol-5-yl)-4'-oxo-3',4'-dihydro-1H,1'H-spiro[pyrrolidine-3,2'-quinazoline]-1-carboxamide
Homo sapiens
-
IC50: 0.051 mM, isozyme IMPDH II
0.119
N-ethyl-7'-methoxy-3'-methyl-6'-(1,3-oxazol-5-yl)-4'-oxo-3',4'-dihydro-1H,1'H-spiro[pyrrolidine-3,2'-quinazoline]-1-carboxamide
Homo sapiens
-
IC50: 0.119 mM, isozyme IMPDH II
0.005
N-methyl-N'-[4-(1,3-oxazol-5-yl)phenyl]-6-phenyl-1,3,5-triazine-2,4-diamine
Homo sapiens
-
isozyme IMPDH II IC50: 0.005 mM
0.005
N-methyl-N'-[4-(4-methyl-1,3-oxazol-5-yl)phenyl]-6-phenyl-1,3,5-triazine-2,4-diamine
Homo sapiens
-
isozyme IMPDH II IC50: 0.005 mM
0.000045
N-methyl-N-[2-(2-[[3-methyl-4-(1,3-oxazol-5-yl)phenyl]amino]-1,3-oxazol-5-yl)phenyl]-3-morpholin-4-ylpropanamide
Homo sapiens
-
isozyme IMPDH II IC50: 45 nM
0.000055
N-tert-butyl-N'-[3-chloro-4-(1,3-oxazol-5-yl)phenyl]ethanediamide
Homo sapiens
-
isozyme IMPDH II IC50: 55 nM
0.00001
N-tert-butyl-N'-[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]ethanediamide
Homo sapiens
-
isozyme IMPDH II IC50: 10 nM
0.005
N-tert-butyl-N'-[4-(1,3-oxazol-5-yl)phenyl]ethanediamide
Homo sapiens
-
isozyme IMPDH II IC50: 0.005 mM
0.005
N-tert-butyl-N'-[4-(4-methyl-1,3-oxazol-5-yl)phenyl]ethanediamide
Homo sapiens
-
isozyme IMPDH II IC50: 0.005 mM
0.000017
N-[1-[6-(4-ethylpiperazin-1-yl)pyridin-3-yl]-1-methylethyl]-2-fluoro-9-oxo-9,10-dihydroacridine-3-carboxamide
Homo sapiens
-
0.000047
N-[2-(2-[[3-(chloromethyl)-4-(1,3-oxazol-5-yl)phenyl]amino]-1,3-oxazol-5-yl)phenyl]-N-methyl-3-morpholin-4-ylpropanamide
Homo sapiens
-
isozyme IMPDH II IC50: 47 nM
0.000028
N-[2-(2-[[3-bromo-4-(1,3-oxazol-5-yl)phenyl]amino]-1,3-oxazol-5-yl)phenyl]-3-hydroxy-N-methylpropanamide
Homo sapiens
-
isozyme IMPDH II IC50: 28 nM
0.000021
N-[2-(2-[[3-bromo-4-(1,3-oxazol-5-yl)phenyl]amino]-1,3-oxazol-5-yl)phenyl]-N-methyl-3-morpholin-4-ylpropanamide
Homo sapiens
-
isozyme IMPDH II IC50: 21 nM
0.000048
N-[2-(2-[[3-chloro-4-(1,3-oxazol-5-yl)phenyl]amino]-1,3-oxazol-5-yl)phenyl]-3-hydroxy-N-methylpropanamide
Homo sapiens
-
isozyme IMPDH II IC50: 48 nM
0.00031
N-[2-(2-[[3-ethyl-4-(1,3-oxazol-5-yl)phenyl]amino]-1,3-oxazol-5-yl)phenyl]-3-hydroxy-N-methylpropanamide
Homo sapiens
-
isozyme IMPDH II IC50: 310 nM
0.000021
N-[2-(2-[[3-ethyl-4-(1,3-oxazol-5-yl)phenyl]amino]-1,3-oxazol-5-yl)phenyl]-N-methyl-3-morpholin-4-ylpropanamide
Homo sapiens
-
isozyme IMPDH II IC50: 21 nM
0.000091
N-[2-(2-[[3-methoxy-4-(1,3-oxazol-4-yl)phenyl]amino]-1,3-oxazol-5-yl)phenyl]-N-methyl-2-morpholin-4-ylacetamide
Homo sapiens
-
isozyme IMPDH II IC50: 91 nM
0.000012
N-[2-(2-[[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]amino]-1,3-oxazol-5-yl)phenyl]-N-methyl-2-morpholin-4-ylacetamide
Homo sapiens
-
0.000016
N-[2-(2-[[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]amino]-1,3-oxazol-5-yl)phenyl]-N-methyl-3-morpholin-4-ylpropanamide
Homo sapiens
-
isozyme IMPDH II IC50: 16 nM
0.000018
N-[2-(hydroxymethyl)cyclopentyl]-N'-[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]propanediamide
Homo sapiens
-
0.005
N-[2-chloro-3-methoxy-4-(1,3-oxazol-5-yl)phenyl]-5-phenyl-1,3-oxazol-2-amine
Homo sapiens
-
isozyme IMPDH II IC50: 0.005 mM
0.0016
N-[2-chloro-5-methoxy-4-(1,3-oxazol-5-yl)phenyl]-5-phenyl-1,3-oxazol-2-amine
Homo sapiens
-
isozyme IMPDH II IC50: 0.0016 mM
0.005
N-[2-fluoro-5-methoxy-4-(1,3-oxazol-5-yl)phenyl]-5-phenyl-1,3-oxazol-2-amine
Homo sapiens
-
isozyme IMPDH II IC50: 0.005 mM
0.00005
N-[3-bromo-4-(1,3-oxazol-5-yl)phenyl]-N'-tert-butylethanediamide
Homo sapiens
-
isozyme IMPDH II IC50: 50 nM
0.005
N-[3-chloro-4-(1,3-oxazol-4-yl)phenyl]-5-phenyl-1,3-oxazol-2-amine
Homo sapiens
-
isozyme IMPDH II IC50: 0.005 mM
0.000088
N-[3-chloro-4-(1,3-oxazol-5-yl)phenyl]-5-phenyl-1,3-oxazol-2-amine
Homo sapiens
-
isozyme IMPDH II IC50: 88 nM
0.00034
N-[3-chloro-4-(1,3-oxazol-5-yl)phenyl]-N'-methyl-6-phenyl-1,3,5-triazine-2,4-diamine
Homo sapiens
-
isozyme IMPDH II IC50: 340 nM
0.01
N-[3-ethoxy-4-(1,3-oxazol-5-yl)phenyl]-5-phenyl-1,3-oxazol-2-amine
Homo sapiens
-
isozyme IMPDH II IC50: 0.010 mM
0.00019
N-[3-methoxy-4-(1,3-oxazol-2-yl)phenyl]-5-phenyl-1,3-oxazol-2-amine
Homo sapiens
-
isozyme IMPDH II IC50: 190 nM
0.000057
N-[3-methoxy-4-(1,3-oxazol-4-yl)phenyl]-5-phenyl-1,3-oxazol-2-amine
Homo sapiens
-
isozyme IMPDH II IC50: 57 nM
0.0016
N-[3-methoxy-4-(1,3-oxazol-4-yl)phenyl]-N'-methyl-6-phenyl-1,3,5-triazine-2,4-diamine
Homo sapiens
-
isozyme IMPDH II IC50: 0.0016 mM
0.00002
N-[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]-5-phenyl-1,3-oxazol-2-amine
Homo sapiens
-
isozyme IMPDH II IC50: 20 nM
0.000076
N-[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]-N'-methyl-6-phenyl-1,3,5-triazine-2,4-diamine
Homo sapiens
-
isozyme IMPDH II IC50: 76 nM
0.00041
N-[3-methoxy-4-(1H-1,2,4-triazol-1-yl)phenyl]-5-phenyl-1,3-oxazol-2-amine
Homo sapiens
-
isozyme IMPDH II IC50: 410 nM
0.002
N-[3-methoxy-4-(2-methyl-1,3-oxazol-5-yl)phenyl]-5-phenyl-1,3-oxazol-2-amine
Homo sapiens
-
isozyme IMPDH II IC50: 0.002 mM
0.005
N-[3-methoxy-4-(4-methyl-1,3-oxazol-5-yl)phenyl]-5-phenyl-1,3-oxazol-2-amine
Homo sapiens
-
isozyme IMPDH II IC50: 0.005 mM
0.005
N-[3-methyl-4-(1,3-oxazol-4-yl)phenyl]-5-phenyl-1,3-oxazol-2-amine
Homo sapiens
-
isozyme IMPDH II IC50: 0.005 mM
0.005
N-[4-(1,3-oxazol-4-yl)phenyl]-5-phenyl-1,3-oxazol-2-amine
Homo sapiens
-
isozyme IMPDH II IC50: 0.005 mM
0.005
N-[4-(1,3-oxazol-5-yl)phenyl]-5-phenyl-1,3-oxazol-2-amine
Homo sapiens
-
isozyme IMPDH II IC50: 0.005 mM
0.002
N-[4-(2,4-dimethyl-1,3-oxazol-5-yl)phenyl]-5-phenyl-1,3-oxazol-2-amine
Homo sapiens
-
isozyme IMPDH II IC50: 0.002 mM
0.005
N-[4-(4-methyl-1,3-oxazol-5-yl)phenyl]-5-phenyl-1,3-oxazol-2-amine
Homo sapiens
-
isozyme IMPDH II IC50: 0.005 mM
0.000016
phenyl N'-cyano-N-(3-[cyano[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]carbamimidamido]benzyl)imidocarbamate
Homo sapiens
-
0.000104
tert-butyl 7'-methoxy-3'-methyl-6'-(1,3-oxazol-5-yl)-4'-oxo-3',4'-dihydro-1H,1'H-spiro[pyrrolidine-3,2'-quinazoline]-1-carboxylate
Homo sapiens
-
IC50: 104 nM, isozyme IMPDH II
0.000035
tert-butyl methyl (1S,4S)-7'-methoxy-3'-methyl-6'-(1,3-oxazol-5-yl)-4'-oxo-3',4'-dihydro-1'H-spiro[cyclopentane-1,2'-quinazoline]-3,4-dicarboxylate
Homo sapiens
-
0.00003
thiazofurin-5'-yl-2-ethyladenosin-5'-yl-difluromethylene bis(phosphonate)
Homo sapiens
pH 8.0, 25°C
0.000014
thiazole-4-carboxamide 2-ethyladenine dinucleotide
Homo sapiens
pH 8.0, 25°C
0.000506
[(1E,3E)-5-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-3-methylpenta-1,3-dien-1-yl]phosphonic acid
Homo sapiens
-
isozyme IMPDH II IC50: 506 nM
0.000168
[(2E)-4-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-2-methylbut-2-en-1-yl]phosphonic acid
Homo sapiens
-
isozyme IMPDH II IC50: 168 nM
0.001
[(2E)-4-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-2-methylbut-2-en-1-yl]phosphoramidic acid
Homo sapiens
-
isozyme IMPDH II IC50: above 0.001 mM
0.000096
[(3E)-5-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-3-methylpent-3-en-1-yl]phosphonic acid
Homo sapiens
-
isozyme IMPDH II IC50: 96 nM
0.00002
[(3E)-5-(6-ethyl-4-hydroxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-3-methylpent-3-en-1-yl]phosphonic acid
Homo sapiens
-
isozyme IMPDH II IC50: 20 nM
0.000086
[(4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-en-1-yl]phosphonic acid
Homo sapiens
-
isozyme IMPDH II IC50: 86 nM
0.000028
(2E)-3-furan-2-yl-N-[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]prop-2-enamide
Homo sapiens
-
0.000028
(2E)-3-furan-2-yl-N-[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]prop-2-enamide
Homo sapiens
-
isozyme IMPDH II IC50: 28 nM
0.000011
Mycophenolic acid
Homo sapiens
-
isozyme IMPDH II IC50: 11 nM, potent, uncompetitive inhibition, immunosuppressive drug, prodrug is mycophenolate mofetil
0.000014
Mycophenolic acid
Homo sapiens
-
potent, uncompetitive, reversible, inhibits both isozymes, prodrug is mycophenolate mofetil, isozyme IMPDH II IC50: 14 nM
0.0000992
Mycophenolic acid
Homo sapiens
-
IC50: 99.2 nM with umbilical vein endothelial cells, 128 nM with Jurkat cells, inhibits the enzyme in vivo and in vitro, mycophenolic acid inhibits tumor-associated angiogenesis and is used as clinical drug in immunosuppression
0.000128
Mycophenolic acid
Homo sapiens
-
IC50: 99.2 nM with umbilical vein endothelial cells, 128 nM with Jurkat cells, inhibits the enzyme in vivo and in vitro, mycophenolic acid inhibits tumor-associated angiogenesis and is used as clinical drug in immunosuppression
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
activity is higher in erythrocytes than in mononuclear cells
additional information
-
activity in whole blood cells after application of prodrug mycophenolate mofetil
additional information
-
the bacterial enzyme shows low activity due to its open dehydrogenase conformation in opposite to the bacterial enzyme which has a closed hydrolase conformation
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
37
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
from healthy adults and paediatric patients on thiopurine therapy
additional information
from healthy adults and paediatric patients on thiopurine therapy
-
isoform IMPDH1 undergoes alternate splicing to produce at least two retinal isoforms. The abundance of isoforms differs between the species
additional information
type II isoform predominates in proliferating cells and is upregulated in neoplastic cells
additional information
type II isoform predominates in proliferating cells and is upregulated in neoplastic cells
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
isoform IMPDH1 undergoes time-dependent proteolysis with the protease-sensitive region mapping within the catalytic domain. Both IMPDH1 and IMPDH2 proteins show reduced proteolysis with pre-incubation of IMP. The presence of ATP results in significant protection of IMPDH1, via a mechanism involving conformational changes upon nucleotide binding to the Bateman domain without affecting catalytic activity. Mutation R224P, responsible for retinitis pigmentosa, abolishes ATP binding and nucleotide protection and this correlates with an altered propensity to cluster
physiological function
metabolism
physiological function
additional information
siRNA knockdown of serine hydroxymethyltransferase-2, SHMT2, or dihydrofolate reductase, DHFR, leads to increased rod and ring (RR) formation. IMPDH-containing RR structures can form in mammalian cells
physiological function
is a key enzyme in the biosynthesis of purine nucleotides. Mutations in the type I gene cause the RP10 form of autosomal dominant retinitis pigmentosa
physiological function
mutations in the CBS subdomain of IMPDH1 account for 2-3% of autosomal dominant retinitis pigmentosa
physiological function
the enzyme selectively inhibits cell and tumor growth of ASCL1Low small cell lung cancer cells
metabolism
isiform IMPDH2 undergoes time-dependent proteolysis with the protease-sensitive region mapping within the catalytic domain. Both IMPDH1 and IMPDH2 proteins show reduced proteolysis with pre-incubation of IMP. The presence of AMP results in significant protection of IMPDH2, via a mechanism involving conformational changes upon nucleotide binding to the Bateman domain without affecting catalytic activity
physiological function
is a key enzyme in the biosynthesis of purine nucleotides
physiological function
-
presence of rs11706052 polymorphism reduces the antiproliferative effect of mycophenolic acid on lymphocytes by approximately 50% compared with the IMPDH2 wild-type form at therapeutic relevant concentrations of 10 microM/l and 25 microM/l
physiological function
inosine monophosphate dehydrogenase (IMPDH), a key enzyme leading to GMP and GTP biosynthesis. Rod and ring (RR) formation from IMP dehydrogenase is regulated through the one-carbon metabolic pathway. RR formation is induced by IMPDH inhibitors as well as glutamine deprivation. Because RR assembly occurs when guanine nucleotide biosynthesis is inhibited, and because RRs rapidly disassemble after the addition of guanine nucleotide precursors, RR formation might be an adaptive homeostatic mechanism, allowing IMPDH to sense changes in the one-carbon folate pathway, detailed overview
physiological function
the enzyme catalyzes a crucial step in the de novo synthesis of guanine nucleotides. It oxidizes inosine 5'-monophosphate (IMP) to xanthosine 5'-monophosphate (XMP) in a nicotinamide adenine dinucleotide (NAD+)-dependent manner. The enzyme has a critical position in the purine biosynthesis pathway
physiological function
increased isoform IMPDH2 enhances RNA polymerase I and III transcription directly linking GTP metabolism to both anabolic capacity as well as nucleolar enlargement historically observed as associated with cancer. Isoform IMPDH2 has the essential function in embryogenesis that cannot be compensated by isoform IMPDH1
physiological function
the enzyme selectively inhibits cell and tumor growth of ASCL1Low small cell lung cancer cells
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). IMDH1_HUMAN
514
0
55406
Swiss-Prot
other Location (Reliability: 2)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
56000
65000
-
x * 56000, canonical isoforms of IMPDH1 and smaller retinal isoform, x * 65000, large retinal isoform, calculated
56000
-
x * 56000, canonical isoforms of IMPDH1 and smaller retinal isoform, x * 65000, large retinal isoform, calculated
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
tetramer
?
-
x * 56000, canonical isoforms of IMPDH1 and smaller retinal isoform, x * 65000, large retinal isoform, calculated
tetramer
additional information
-
the C-terminal extension unique to the retinal isoforms of IMPDH blocks the nucleic acid binding site
tetramer
-
the enzyme forms a homotetramer with four active sites and an open dehydrogenase conformation
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
modeling of complex with inhibitor 9-(5-O-[hydroxy[([hydroxy[2-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)ethoxy]phosphoryl]oxy)methyl]phosphoryl]-b-L-ribofuranosyl)-9H-purin-6-amine
type I isoform, in complex with 6-chloropurine riboside 5'-monophosphate at 2.5 A resolution
enzyme type II complexed with 6-Cl-IMP and selenazole-4-carboxamide adenine dinucleotide, no method mentioned
isoform IMPDH2 in complex with GTP, hanging drop vapor diffusion method, using 25% PEG-1500 and 0.1 M buffer MIB (malonic acid, imidazole and boric acid) at pH 9.0. Isoform IMPDH2 in complex with GDP, hanging drop vapor diffusion method, using 25% PEG-1500 and 0.1 M sodium citrate at pH 5.5, 0.2 M lithium sulfate and 15% (v/v) ethanol
modeling of complex with inhibitor 9-(5-O-[hydroxy[([hydroxy[2-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)ethoxy]phosphoryl]oxy)methyl]phosphoryl]-b-L-ribofuranosyl)-9H-purin-6-amine
type 1 in complex with inhibitor 6-Cl-inosine 5'-phosphate, at 2.6 A resolution, type 2 in complex with inhibitor 6-Cl-inosine 5'-phosphate and SAD or NAD, at 2.9 A resolution, and with inhibitors ribavirin-monophosphate and C2-mycophenolic adenine nucleotide, at 2.65 A resolution
-
type II isoform, in complex with 6-chloropurine riboside 5'-monophosphate and selenazole-4-carboxyamide-adenine dinucleotide at 2.9 A resolution, in complex with ribavirin monophosphate and phosphonic acidmono-[2-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-ethyl] ester at 2.65 resolution, in complex with with 6-chloropurine riboside 5'-monophosphate and NAD+ at 2.9 A resolution
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A285T
site-directed mutagenesis of IMPDH1, similar activity and protein stability compared to the wild-type enzyme
D226N
H372P
IMPDH1 polymorphism, which is associated with retinal degeneration
N198K
IMPDH1 polymorphism, which is associated with retinal degeneration and with Leber congenital amaurosis
R105W
IMPDH1 polymorphism, which is associated with retinal degeneration and with Leber congenital amaurosis
R224P
R231P
IMPDH1 polymorphism, which causes autosomal dominant retinitis pigmentosa
T116M
IMPDH1 polymorphism, which is associated with retinal degeneration
V268I
C331A
-
mutated type 2 isozyme in the inosine 5'-phosphate binding site, which results in less than 0.1% activity
D226N
D364A
-
mutated type 2 isozyme in the inosine 5'-phosphate binding site, which results in less than 0.1% activity
G326A
-
mutated type 2 isozyme in the inosine 5'-phosphate binding site, which results in less than 0.1% activity
K238E
the mutant enzyme cannot be allosterically inhibited in vitro neither by GTP/GDP
L227P
the mutant enzyme cannot be allosterically inhibited in vitro neither by GTP/GDP
L263F
N198K
the mutant enzyme cannot be allosterically inhibited in vitro neither by GTP/GDP
Q441E
-
less than 0.045% of wild type activity, therefore no further characterization possible
R224P
the mutant enzyme cannot be allosterically inhibited in vitro neither by GTP/GDP
R231P
the mutant enzyme cannot be allosterically inhibited in vitro neither by GTP/GDP
R322K
-
less than 0.045% of wild type activity, therefore no further characterization possible
R322K/Q441E
-
less than 0.045% of wild type activity, therefore no further characterization possible
S329A
-
mutated type 2 isozyme, increases the Km for both inosine 5'-phosphate and NAD without altering kcat
Y12A
the mutation abrogates polymerization of the enzyme. Mutant enzymes remain as monodisperse tetramers in solution
additional information
D226N
naturally occuring mutation causing autosomal dominant retinitis pigmentosa, site-directed mutagenesis of IMPDH1, similar activity and protein stability compared to the wild-type enzyme
D226N
IMPDH1 polymorphism, which is associated with retinal degeneration
R224P
naturally occuring mutation causing autosomal dominant retinitis pigmentosa, site-directed mutagenesis of IMPDH1, the mutant shows altered subcellular localization compared to the wild-type enzyme, similar activity and protein stability compared to the wild-type enzyme
R224P
IMPDH1 polymorphism, which is associated with retinal degeneration
V268I
site-directed mutagenesis of IMPDH1, pathogenic mutation, the mutant shows altered subcellular localization compared to the wild-type enzyme, similar activity and protein stability compared to the wild-type enzyme
V268I
IMPDH1 polymorphism, which is associated with retinal degeneration
D226N
-
mutant of isoform IMPDH1(546), and mutant of isoform IMPDH1(595), both are localized to cytosol and exhibit kinetic parameters identical to wild-type
D226N
the mutant enzyme cannot be allosterically inhibited in vitro neither by GTP/GDP
L263F
IMPDH2 polymorphism, which decreases the value of kcat by a factor of 10
additional information
-
construction of umbilical vein endothelial cell IMPDH-1 knockout lines
additional information
-
identification of nine genetic variants in type II enzyme
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant wild-type and mutant IMPDH1s from Escherichia coli strain H712 by two steps of affinity chromatography, and gel filtration, to over 95% purity
native enzyme from MCF7 cells partially by gel filtration, recombinant His-tagged type II IMPDH from Escherichia coli strain BL21(DE3) by nickel affinity chromatography
-
recombinant full-length type I isozyme from Escherichia coli by two steps of affinity chromatography, recombinant His-tagged type I isozyme subdomain from Escherichia coli by metal affinity chromatography and ammonium sulfate fractionation
-
recombinant isoyzmes IMPDH I and IMPDH II from Escherichia coli strain BL21(DE3) by two steps of ion exchange chromatography
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of wild-type and mutant IMPDH1s in enzyme-deficient Escherichia coli strain H712 and in HeLa cells, in the latter as GFP-fusion proteins
expressed in Escherichia coli BL21(DE3) cells
expression as fusion protein with green fluorescence protein, in HEK-293 cell, HeLa cell and COS cell, and expression in Escherichia coli
-
expression of full-length type I isozyme and of the His-tagged type I isozyme subdomain in Escherichia coli
-
expression of isoyzmes IMPDH I and IMPDH II in Escherichia coli strain BL21(DE3)
-
gene IMPDH2, recombinant expression in Escherichia coli strain BL21(DE3), subcloning in Escherichia coli strain DH5alpha
overexpression of IMPDH2 in human erythroleukemia K562 cells, expression analysis, the enzyme expression affects the cytotoxicity of methotrexate, overview
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
enhanced expression of the type 2 isozyme in leukemias and other proliferating human cells
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
diagnostics
IMPDH activity is measured in adults without thiopurine treatment as well as in adult and paediatric patients treated with thiopurines. A wide interindividual variability in IMPDH activity in erythrocytes is observed. No difference in IMPDH activity is found between untreated subjects and adult and paediatric patients on thiopurine therapy. The method described is useful in the determination of IMPDH phenotype from patients on thiopurine therapy and in the investigation of the potential relationship between IMPDH activity in erythrocytes and the occurrence of adverse events and drug response variability
drug development
type I IMPDH is identified as an antiangiogenic drug target. Inhibition may cause endothelial cell cycle arrest
analysis
-
real-time reverse-transcription PCR assay for mRNA quantification of isoforms IMPDH1 and IMPDH2 in blood samples and cultured cells. Limits of detection and quantification are 10 and 1000 copies of cDNA per reaction, respectively
diagnostics
IMPDH activity is measured in adults without thiopurine treatment as well as in adult and paediatric patients treated with thiopurines. A wide interindividual variability in IMPDH activity in erythrocytes is observed. No difference in IMPDH activity is found between untreated subjects and adult and paediatric patients on thiopurine therapy. The method described is useful in the determination of IMPDH phenotype from patients on thiopurine therapy and in the investigation of the potential relationship between IMPDH activity in erythrocytes and the occurrence of adverse events and drug response variability
drug development
medicine
pharmacology
-
the enzyme is a potential target as modulators in MTX chemotherapy of resistant cells, overview
drug development
-
the enzyme is a target for drug development in treatment of structural schizophrenia
drug development
-
the enzyme is a target in enzyme-pattern-targeted chemotherapy in acuet leukemia, AML, treatment
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
drug development
IMPDH2 is the major target for cancer chemotherapy
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
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
medicine
-
the enzyme is a target for immunosuppression therapy suing mycophenolic acid, prodrug is mycophenolate mofetil
medicine
-
changes in expression of IMPDH1 and IMPDH2 in patient samples after initiation of an immunosuppressive regimen that includes calcineurin inhibitors, mycophenolate mofetil, and stroids
medicine
-
in patients with kidney transplantation, type I IMPDH activity and gene expression increases during the first three months following transplantation and reaches its maximal level during acute rejection episodes, whereas type II mRNA is stable. Patients with a prolonged mycophenolate mofetil treatment exhibit an increase in the induction potency of both IMPDH activity and gene expression. Measurement of IMPDH mRNAs may provide reliable information to predict acute rejection
medicine
-
in renal transplant patients, transplantation and initiation of immunosuppressive therapy is associated with increased isoform IMPDH1 and decreased IMPDH2 expression. In CD4+ cells, however, IMPDH2 expression increases. Two weeks posttransplant, mycophenolic acid-treated patients display elevated IMPDH1 and IMPDH2 expression in reticulocyte. Patients with acute rejection during follow-up demonstrate higher IMPDH2 expression in Cd4+ cells pretransplant than nonrejecting patients
medicine
-
in stable kidney transplant recipients, inosine 5'-phosphate dehydrogenase activity is 17.5 versus 46.6 nmol XMP/h/microgramm protein in diabetic and nondiabetic patients, respectively. Activity in diabetic patients is significantly lower irrespective of concomitant therapy with cyclosporine or tacrolimus and independent of the bound or unbound mycophenolic acid
medicine
-
study on inosine 5'-phosphate activity in thiopurine-treated patients with inflammatory bowel disease. Negative correlation between inosine 5'-phosphate dehydrogenase activity and dose-normalized 6-methylthioinosine concentrations, no evident correlation to 6-thioguanine nucleotide or the 6-methylthioinosine/6-thioguanine nucleotide ratio
medicine
-
a poorer response to mycophenolic acid therapy in some individuals may be due to the presence of the rs11706052 polymorphism
medicine
-
IMPDH activity in erythrocytes may be useful indicator of short-term immunosuppression and long-term exposure of the immunosuppressant mycophenolic acid
medicine
-
modified method for the measurement of IMPDH activity, that is less labor-intensive, more robust in general, and capable of yielding a better reproducibility, which can be used reliably in multicenter trials and in longitudinal studies to evaluate the additional value of any pharmacodynamic monitoring among a diversity of patients treated with mycophenolic acid
medicine
-
study on a target range for inosine 5'-monophosphate dehydrogenase activity in maintenance therapy with tacrolimus, on patients with renal transplants and healthy volunteers. Inosine 5'-monophosphate dehydrogenase activity in cell lysates can be reliably determined indirectly by measuring xanthosine 5'-monophophate in cell lysates supplemented with IMP and beta-nicotine adenine dinucleotide using an HPLC method. Cell lysates show a 5-6 nmol /l IC50 mycophenolic acid concentration. Tacrolimus, cyclosporine and prednisolone do not affect IMPDH activity. The peak mycophenolic acid concentration is achieved at 1 h after dosing. IMPDH activity decreases to 75% and 67% at 1 and 2 h after dosing respectively
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Collart, F.R.; Huberman, E.
Cloning and sequence analysis of the human and Chinese hamster inosine-5-monophosphate dehydrogenase cDNAs
J. Biol. Chem.
263
15769-15772
1988
Cricetulus griseus, Homo sapiens
Lui, M.S.; Faderan, M.A.; Liepnieks, J.J.; Natsumeda, Y.; Olah, E.; Jayaram, H.N.; Weber, G.
Modulation of IMP dehydrogenase activity and guanylate metabolism by tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide)
J. Biol. Chem.
259
5078-5082
1984
Homo sapiens
Weber, G.; Yamaji, Y.; Olah, E.; Natsumeda, Y.; Jayaram, H.N.; Lapis, E.; Zhen, W.; Prajda, N.; Hoffman, R.; Tricot, G.J.
Clinical and molecular impact of inhibition of IMP dehydrogenase activity by tiazofurin
Adv. Enzyme Regul.
28
335-356
1989
Homo sapiens, Rattus norvegicus
Yamada, Y.; Goto, H.; Yoshino, M.; Ogasawara, N.
IMP dehydrogenase and action of antimetabolites in human cultured blast cells
Biochim. Biophys. Acta
1051
209-214
1990
Homo sapiens
Holmes, E.W.; Pehlke, D.M.; Kelley, W.N.
Human IMP dehydrogenase. Kinetics and regulatory properties
Biochim. Biophys. Acta
364
209-217
1974
Homo sapiens
Hager, P.W.; Collafrt, F.R.; Huberman, E.; Bitchell, B.S.
Recombinant human inosine monophosphate dehydrogenase type I and type II proteins
Biochem. Pharmacol.
49
1323-1329
1995
Homo sapiens
Nelson, P.H.; Carr, S.F.; Devens, B.H.; Eugui, E.M.; Franco, F.; Gonzalez, C.; Hawley, R.C.; Loughhead, D.G.; Milan, D.J.; Papp, E.; Patterson, J.W.; Rouhafza, S.; Sjogren, E.B.; Smith, D.B.; Stephenson, R.A.; Talamas, F.X.; Wastos, A.M.; Weikert, R.J.;
Structure-activity relationships for inhibition of inosine monophosphate dehydrogenase by nuclear variants of mycophenolic acid
J. Med. Chem.
39
4181-4196
1996
Homo sapiens
Xiang,B.; Taylor, J.C.; Markham, G.D.
Monovalent cation activation and kinetic mechanism of inosine 5'-monophosphate dehydrogenase
J. Biol. Chem.
271
1435-1440
1996
Homo sapiens
Griesmacher, A.; Weigel, G.; Seebacher, G.; Muller, M.M.
IMP-dehydrogenase inhibition in human lymphocytes and lymphoblasts by mycophenolic acid and mycophenolic acid glucuronide
Clin. Chem.
43
2312-2317
1997
Homo sapiens
Farazi, t.; Leichman, J.; Harris, T.; Cahoon, M.; Hedstrom, L.
Isolation and characterization onf mycophenolic acid-resistant mutants of inosine-5'-monophosphate dehydrogenase
J. Biol. Chem.
272
961-965
1997
Homo sapiens
Carr, S.F.; Papp, E.; Wu, J.C.; Natsumeda, Y.
Characterization of human type I and type II IMP dehydrogenases
J. Biol. Chem.
36
27286-27290
1993
Homo sapiens
Goldstein, B.M.; Colby, T.D.
IMP dehydrogenase: Structural aspects of inhibitor binding
Curr. Med. Chem.
6
519-536
1999
Borreliella burgdorferi, Cricetulus griseus, Homo sapiens, Streptococcus pyogenes, Tritrichomonas suis
Hedstrom, L.
IMP dehydrogenase: Mechanism of action and inhibition
Curr. Med. Chem.
6
545-560
1999
Borreliella burgdorferi, Escherichia coli, Eimeria tenella, Homo sapiens, Rattus norvegicus, Tritrichomonas suis
Digits J.A.; Hedstrom L.
Species-specific inhibition of inosine 5'-monophosphate dehydrogenase by mycophenolic acid
Biochemistry
38
15388-15397
1999
Homo sapiens, Tritrichomonas suis
Barnes, B.J.; Eakin, A.E.; Izydore, R.A.; Hall, I.H.
Implications of selective type II IMP dehydrogenase (IPDH) inhibition by the 6-ethoxycarbonyl-3,3-disubstituted-1,5-diazabicyclo[3.1.0.]hexane-2,4-diones on tumor cell death
Biochem. Pharmacol.
62
91-100
2001
Homo sapiens
Albrecht,W.; Storck, M.; Pretsch, E.; Martin, W.; Abendroth, D.
Development and application of a hight-performance liquid chromatography-based assay for determination of the activity of inosine 5'-monophosphate dehydrogenase in whole blood and isolated mononuclear cells
Ther. Drug Monit.
22
283-294
2000
Homo sapiens
Colby, T.D.; Vanderveen, K.; Strickler, M.D.; Markham, G.D.; Goldstein, B.M.
Crystal structure of human type II inosine monophosphate dehydrogenase: Implications for ligand binding and drug design
Proc. Natl. Acad. Sci. USA
30
3531-3536
1999
Homo sapiens (P12268), Homo sapiens
McLean, J.E.; Hamaguchi, N.; Belenky, P.; Mortimer, S.E.; Stanton, M.; Hedstrom, L.
Inosine 5'-monophosphate dehydrogenase binds nucleic acids in vitro and in vivo
Biochem. J.
379
243-251
2004
Escherichia coli, Homo sapiens, Tritrichomonas suis
Mortimer, S.E.; Hedstrom, L.
Autosomal dominant retinitis pigmentosa mutations in inosine 5-monophosphate dehydrogenase type I disrupt nucleic acid binding
Biochem. J.
390
41-47
2005
Homo sapiens (P20839)
Franchetti, P.; Cappellacci, L.; Pasqualini, M.; Petrelli, R.; Jayaprakasan, V.; Jayaram, H.N.; Boyd, D.B.; Jain, M.D.; Grifantini, M.
Synthesis, conformational analysis, and biological activity of new analogues of thiazole-4-carboxamide adenine dinucleotide (TAD) as IMP dehydrogenase inhibitors
Bioorg. Med. Chem.
13
2045-2053
2005
Homo sapiens
Iwanowicz, E.J.; Watterson, S.H.; Guo, J.; Pitts, W.J.; Dhar, T.G.M.; Shen, Z.; Chen, P.; Gu, H.H.; Fleener, C.A.; Rouleau, K.A.; Cheney, D.L.; Townsend, R.M.; Hollenbaugh, D.M.
Inhibitors of inosine monophosphate dehydrogenase: SARs about the N-[3-methoxy-4-(5-oxazolyl)phenyl] moiety
Bioorg. Med. Chem. Lett.
13
2059-2063
2003
Homo sapiens
Dhar, T.G.M.; Shen, Z.; Gu, H.H.; Chen, P.; Norris, D.; Watterson, S.H.; Ballentine, S.K.; Fleener, C.A.; Rouleau, K.A.; Barrish, J.C.; Townsend, R.; Hollenbaugh, D.L.; Iwanowicz, E.J.
3-Cyanoindole-based inhibitors of inosine monophosphate dehydrogenase: synthesis and initial structureactivity relationships
Bioorg. Med. Chem. Lett.
13
3557-3560
2003
Homo sapiens
Watterson,S.H.; Carlsen, M.; Dhar, T.G.M.; Shen, Z.; Pitts, W.J.; Guo, J.; Gu, H.H.; Norris, D.; Chorba, J.; Chen, P.; Cheney, D.; Witmer, M.; Fleener, C.A.; Rouleau, K.; Townsend, R.; Hollenbaugh D.L.; Iwanowicz, E.J.
Novel inhibitors of IMPDH: a highly potent and selective quinolone-based series
Bioorg. Med. Chem. Lett.
13
543-546
2003
Homo sapiens
Birch, H.L.; Buckley, G.M.; Davies, N.; Dyke, H.J.; Frost, E.J.; Gilbert, P.J.; Hannah, D.R.; Haughan, A.F.; Madigan, M.J.; Morgan, T.; Pitt, W.R.; Ratcliffe, A.J.; Ray, N.C.; Richard, M.D.; Sharpe, A.; Taylor, A.J.; Whitworth, J.M.; Williams, S.C.
Novel 7-methoxy-6-oxazol-5-yl-2,3-dihydro-1H-quinazolin-4-ones as IMPDH inhibitors
Bioorg. Med. Chem. Lett.
15
5335-5339
2005
Homo sapiens
Buckley, G.M.; Davies, N.; Dyke, H.J.; Gilbert, P.J.; Hannah, D.R.; Haughan, A.F.; Hunt, C.A.; Pitt, W.R.; Profit, R.H.; Ray, N.C.; Richard, M.D.; Sharpe, A.; Taylor, A.J.; Whitworth, J.M.; Williams, S.C.
Quinazolinethiones and quinazolinediones, novel inhibitors of inosine monophosphate dehydrogenase: synthesis and initial structure-activity relationships
Bioorg. Med. Chem. Lett.
15
751-754
2005
Homo sapiens
Beevers, R.E.; Buckley, G.M.; Davies, N.; Fraser, J.L.; Galvin, F.C.; Hannah, D.R.; Haughan, A.F.; Jenkins, K.; Mack, S.R.; Pitt, W.R.; Ratcliffe, A.J.; Richard, M.D.; Sabin, V.; Sharpe, A.; Williams, S.C.
Low molecular weight indole fragments as IMPDH inhibitors
Bioorg. Med. Chem. Lett.
16
2535-2538
2006
Homo sapiens
Watkins, W.J.; Chen, J.M.; Cho, A.; Chong, L.; Collins, N.; Fardis, M.; Huang, W.; Hung, M.; Kirschberg, T.; Lee, W.A.; Liu, X.; Thomas, W.; Xu, J.; Zeynalzadegan, A.; Zhang, J.
Phosphonic acid-containing analogues of mycophenolic acid as inhibitors of IMPDH
Bioorg. Med. Chem. Lett.
16
3479-3483
2006
Homo sapiens
Dubsky, P.C.; Friedl, J.; Stift, A.; Bachleitner-Hofmann, T.; Jakesz, R.; Gnant, M.F.; Weigel, G.
Inosine 5-monophosphate dehydrogenase inhibition by mycophenolic acid impairs maturation and function of dendritic cells
Clin. Chim. Acta
364
139-147
2006
Homo sapiens
Hedstrom, L.; Gan, L.
IMP dehydrogenase: structural schizophrenia and an unusual base
Curr. Opin. Chem. Biol.
10
520-525
2006
Homo sapiens, Tritrichomonas suis
Ji, Y.; Gu, J.; Makhov, A.M.; Griffith, J.D.; Mitchell, B.S.
Regulation of the interaction of inosine monophosphate dehydrogenase with mycophenolic acid by GTP
J. Biol. Chem.
281
206-212
2006
Homo sapiens
Chong, C.R.; Qian, D.Z.; Pan, F.; Wei, Y.; Pili, R.; Sullivan, D.J.; Liu, J.O.
Identification of type 1 inosine monophosphate dehydrogenase as an antiangiogenic drug target
J. Med. Chem.
49
2677-2680
2006
Homo sapiens
Rejman, D.; Olesiak, M.; Chen, L.; Patterson, S.E.; Wilson, D.; Jayaram, H.N.; Hedstrom, L.; Pankiewicz, K.W.
Novel methylenephosphophosphonate analogues of mycophenolic adenine dinucleotide. Inhibition of inosine monophosphate dehydrogenase
J. Med. Chem.
49
5018-5022
2006
Homo sapiens
Penuelas, S.; Noe, V.; Morales, R.; Ciudad, C.J.
Sensitization of human erythroleukemia K562 cells resistant to methotrexate by inhibiting IMPDH
Med. Sci. Monit.
11
BR6-BR12
2005
Homo sapiens
Vethe, N.T.; Mandla, R.; Line, P.D.; Midtvedt, K.; Hartmann, A.; Bergan, S.
Inosine monophosphate dehydrogenase activity in renal allograft recipients during mycophenolate treatment
Scand. J. Clin. Lab. Invest.
66
31-44
2006
Homo sapiens
Xu, D.; Cobb, G.; Spellicy, C.J.; Bowne, S.J.; Daiger, S.P.; Hedstrom, L.
Retinal isoforms of inosine 5-monophosphate dehydrogenase type 1 are poor nucleic acid binding proteins
Arch. Biochem. Biophys.
472
100-104
2008
Homo sapiens
Chen, L.; Petrelli, R.; Olesiak, M.; Wilson, D.J.; Labello, N.P.; Pankiewicz, K.W.
Bis(sulfonamide) isosters of mycophenolic adenine dinucleotide analogues: Inhibition of inosine monophosphate dehydrogenase
Bioorg. Med. Chem.
16
7462-7469
2008
Homo sapiens (P12268), Homo sapiens
Haglund, S.; Taipalensuu, J.; Peterson, C.; Almer, S.
IMPDH activity in thiopurine-treated patients with inflammatory bowel disease - relation to TPMT activity and metabolite concentrations
Br. J. Clin. Pharmacol.
65
69-77
2008
Homo sapiens
Bremer, S.; Rootwelt, H.; Bergan, S.
Real-time PCR determination of IMPDH1 and IMPDH2 expression in blood cells
Clin. Chem.
53
1023-1029
2007
Homo sapiens
Sanquer, S.; Maison, P.; Tomkiewicz, C.; Macquin-Mavier, I.; Legendre, C.; Barouki, R.; Lang, P.
Expression of inosine monophosphate dehydrogenase type I and type II after mycophenolate mofetil treatment: a 2-year follow-up in kidney transplantation
Clin. Pharmacol. Ther.
83
328-335
2008
Homo sapiens
Chen, L.; Gao, G.; Felczak, K.; Bonnac, L.; Patterson, S.E.; Wilson, D.; Bennett, E.M.; Jayaram, H.N.; Hedstrom, L.; Pankiewicz, K.W.
Probing binding requirements of type I and type II isoforms of inosine monophosphate dehydrogenase with adenine-modified nicotinamide adenine dinucleotide analogues
J. Med. Chem.
50
5743-5751
2007
Homo sapiens
Chen, L.; Wilson, D.; Jayaram, H.N.; Pankiewicz, K.W.
Dual inhibitors of inosine monophosphate dehydrogenase and histone deacetylases for cancer treatment
J. Med. Chem.
50
6685-6691
2007
Homo sapiens
Spellicy, C.J.; Daiger, S.P.; Sullivan, L.S.; Zhu, J.; Liu, Q.; Pierce, E.A.; Bowne, S.J.
Characterization of retinal inosine monophosphate dehydrogenase 1 in several mammalian species
Mol. Vis.
13
1866-1872
2007
Canis lupus familiaris, Ovis aries, Homo sapiens, Mus musculus, Rattus norvegicus
Wang, J.; Zeevi, A.; Webber, S.; Girnita, D.M.; Addonizio, L.; Selby, R.; Hutchinson, I.V.; Burckart, G.J.
A novel variant L263F in human inosine 5-monophosphate dehydrogenase 2 is associated with diminished enzyme activity
Pharmacogenet. Genomics
17
283-290
2007
Homo sapiens
Vethe, N.T.; Bremer, S.; Bergan, S.
IMP dehydrogenase basal activity in MOLT-4 human leukaemia cells is altered by mycophenolic acid and 6-thioguanosine
Scand. J. Clin. Lab. Invest.
68
277-285
2007
Homo sapiens
Patel, C.G.; Richman, K.; Yang, D.; Yan, B.; Gohh, R.Y.; Akhlaghi, F.
Effect of Diabetes mellitus on mycophenolate sodium pharmacokinetics and inosine monophosphate dehydrogenase activity in stable kidney transplant recipients
Ther. Drug Monit.
29
735-742
2007
Homo sapiens
Bremer, S.; Mandla, R.; Vethe, N.T.; Rasmussen, I.; Rootwelt, H.; Line, P.D.; Midtvedt, K.; Bergan, S.
Expression of IMPDH1 and IMPDH2 after transplantation and initiation of immunosuppression
Transplantation
85
55-61
2008
Homo sapiens
Pimkin, M.; Markham, G.
Inosine 5-monophosphate dehydrogenase
Adv. Enzymol. Relat. Areas Mol. Biol.
76
1-53
2009
Klebsiella aerogenes, Borreliella burgdorferi, Saccharomyces cerevisiae, Candida albicans, Cricetulus griseus, Cryptosporidium parvum, Escherichia coli, Homo sapiens, Mus musculus, Streptococcus pyogenes, Tritrichomonas suis
Riera, T.V.; Wang, W.; Josephine, H.R.; Hedstrom, L.
A kinetic alignment of orthologous inosine-5-monophosphate dehydrogenases
Biochemistry
47
8689-8696
2008
Cryptosporidium parvum, Homo sapiens
Hedstrom, L.
IMP dehydrogenase: Structure, mechanism, and inhibition
Chem. Rev.
109
2903-2928
2009
Klebsiella aerogenes, Candida albicans, Cricetulus griseus, Escherichia coli, Eimeria tenella, Staphylococcus aureus, Plasmodium falciparum, Pyrococcus horikoshii, Toxoplasma gondii, no activity in Giardia lamblia, no activity in Trichomonas vaginalis, Streptococcus pyogenes (P0C0H6), Homo sapiens (P12268), Homo sapiens (P20839), Leishmania donovani (P21620), Borreliella burgdorferi (P49058), Tritrichomonas suis (P50097), Trypanosoma brucei (P50098), Pneumocystis carinii (Q12658), Cryptosporidium parvum (Q8T6T2)
Gensburger, O.; Picard, N.; Marquet, P.
Effect of mycophenolate acyl-glucuronide on human recombinant type 2 inosine monophosphate dehydrogenase
Clin. Chem.
55
986-993
2009
Homo sapiens
Mino, Y.; Naito, T.; Otsuka, A.; Ozono, S.; Kagawa, Y.; Kawakami, J.
Inosine monophosphate dehydrogenase activity depends on plasma concentrations of mycophenolic acid and its glucuronides in kidney transplant recipients
Clin. Chim. Acta
409
56-61
2009
Homo sapiens
Bairagya, H.R.; Mukhopadhyay, B.P.; Sekar, K.
An insight to the dynamics of conserved water molecular triad in IMPDH II (human): recognition of cofactor and substrate to catalytic Arg 322
J. Biomol. Struct. Dyn.
27
149-158
2009
Homo sapiens (P12268), Homo sapiens
Shu, Q.; Nair, V.
Inosine monophosphate dehydrogenase (IMPDH) as a target in drug discovery
Med. Res. Rev.
28
219-232
2008
Borreliella burgdorferi, Cricetulus griseus, Escherichia coli, Leishmania donovani, Mycobacterium tuberculosis, Mus musculus, Rattus norvegicus, Streptococcus pyogenes, Thermotoga maritima, Tritrichomonas suis, Pyrococcus horikoshii OT3, Homo sapiens (P12268), Homo sapiens (P20839)
Winnicki, W.; Weigel, G.; Sunder-Plassmann, G.; Bajari, T.; Winter, B.; Herkner, H.; Sengoelge, G.
An inosine 5-monophosphate dehydrogenase 2 single-nucleotide polymorphism impairs the effect of mycophenolic acid
Pharmacogenomics J.
10
70-76
2010
Homo sapiens
Brandhorst, G.; Marquet, P.; Shaw, L.M.; Liebisch, G.; Schmitz, G.; Coffing, M.J.; Domke, I.; Streit, F.; Luthe, H.; Oellerich, M.
Multicenter evaluation of a new inosine monophosphate dehydrogenase inhibition assay for quantification of total mycophenolic acid in plasma
Ther. Drug Monit.
30
428-433
2008
Homo sapiens
Glander, P.; Sombogaard, F.; Budde, K.; van Gelder, T.; Hambach, P.; Liefeldt, L.; Lorkowski, C.; Mai, M.; Neumayer, H.H.; Vulto, A.G.; Mathot, R.A.
Improved assay for the nonradioactive determination of inosine 5-monophosphate dehydrogenase activity in peripheral blood mononuclear cells
Ther. Drug Monit.
31
351-359
2009
Homo sapiens
Mitsuhashi, S.; Takenaka, J.; Iwamori, K.; Nakajima, N.; Ubukata, M.
Structure-activity relationships for inhibition of inosine monophosphate dehydrogenase and differentiation induction of K562 cells among the mycophenolic acid derivatives
Bioorg. Med. Chem.
18
8106-8111
2010
Homo sapiens (P12268), Homo sapiens (P20839)
Felczak, K.; Chen, L.; Wilson, D.; Williams, J.; Vince, R.; Petrelli, R.; Jayaram, H.N.; Kusumanchi, P.; Kumar, M.; Pankiewicz, K.W.
Cofactor-type inhibitors of inosine monophosphate dehydrogenase via modular approach: Targeting the pyrophosphate binding sub-domain
Bioorg. Med. Chem.
19
1594-1605
2011
Homo sapiens (P12268), Homo sapiens (P20839), Homo sapiens
Dairaku, I.; Han, Y.; Yanaka, N.; Kato, N.
Inhibitory effect of curcumin on IMP dehydrogenase, the target for anticancer and antiviral chemotherapy agents
Biosci. Biotechnol. Biochem.
74
185-187
2010
Homo sapiens, Mus musculus (P24547)
Maiguma, T.; Yosida, T.; Otsubo, K.; Okabe, Y.; Sugitani, A.; Tanaka, M.; Oishi, R.; Teshima, D.
Evaluation of inosin-5-monophosphate dehydrogenase activity during maintenance therapy with tacrolimus
J. Clin. Pharm. Ther.
35
79-85
2010
Homo sapiens
Chen, L.; Wilson, D.J.; Xu, Y.; Aldrich, C.C.; Felczak, K.; Sham, Y.Y.; Pankiewicz, K.W.
Triazole-linked inhibitors of inosine monophosphate dehydrogenase from human and Mycobacterium tuberculosis
J. Med. Chem.
53
4768-4778
2010
Homo sapiens (P12268), Homo sapiens (P20839), Homo sapiens, Mycobacterium tuberculosis, Mycobacterium tuberculosis H37Rv
Thomas, E.C.; Gunter, J.H.; Webster, J.A.; Schieber, N.L.; Oorschot, V.; Parton, R.G.; Whitehead, J.P.
Different characteristics and nucleotide binding properties of inosine monophosphate dehydrogenase (IMPDH) isoforms
PLoS ONE
7
e51096
2012
Homo sapiens (P12268), Homo sapiens (P20839), Homo sapiens
Calise, S.J.; Purich, D.L.; Nguyen, T.; Saleem, D.A.; Krueger, C.; Yin, J.D.; Chan, E.K.
Rod and ring formation from IMP dehydrogenase is regulated through the one-carbon metabolic pathway
J. Cell Sci.
129
3042-3052
2016
Homo sapiens (P12268)
Beringer, A.; Citterio-Quentin, A.; Otero, R.O.; Gustin, C.; Clarke, R.; Salvi, J.P.; Boulieu, R.
Determination of inosine 5-monophosphate dehydrogenase activity in red blood cells of thiopurine-treated patients using HPLC
J. Chromatogr. B
1044-1045
194-199
2017
Homo sapiens (P12268), Homo sapiens (P20839), Homo sapiens
Dunkern, T.; Chavan, S.; Bankar, D.; Patil, A.; Kulkarni, P.; Kharkar, P.S.; Prabhu, A.; Goebel, H.; Rolser, E.; Burckhard-Boer, W.; Arumugam, P.; Makhija, M.T.
Design, synthesis and biological evaluation of novel inosine 5-monophosphate dehydrogenase (IMPDH) inhibitors
J. Enzyme Inhib. Med. Chem.
29
408-419
2014
Homo sapiens (P12268), Homo sapiens
Cholewinski, G.; Iwaszkiewicz-Grzes, D.; Prejs, M.; Glowacka, A.; Dzierzbicka, K.
Synthesis of the inosine 5'-monophosphate dehydrogenase (IMPDH) inhibitors
J. Enzyme Inhib. Med. Chem.
30
550-563
2015
Homo sapiens (P12268), Homo sapiens (P20839)
Lee, S.; Ku, A.F.; Vippila, M.R.; Wang, Y.; Zhang, M.; Wang, X.; Hedstrom, L.; Cuny, G.D.
Mycophenolic anilides as broad specificity inosine-5-monophosphate dehydrogenase (IMPDH) inhibitors
Bioorg. Med. Chem. Lett.
30
127543
2020
Cryptosporidium parvum, Homo sapiens (P12268), Homo sapiens
Huang, F.; Ni, M.; Chalishazar, M.D.; Huffman, K.E.; Kim, J.; Cai, L.; Shi, X.; Cai, F.; Zacharias, L.G.; Ireland, A.S.; Li, K.; Gu, W.; Kaushik, A.K.; Liu, X.; Gazdar, A.F.; Oliver, T.G.; Minna, J.D.; Hu, Z.; DeBerardinis, R.J.
Inosine monophosphate dehydrogenase dependence in a subset of small cell lung cancers
Cell Metab.
28
369-382.e5
2018
Homo sapiens (P12268), Homo sapiens (P20839)
Yu, R.; Kim, Y.; Maltseva, N.; Braunstein, P.; Joachimiak, A.; Hedstrom, L.
Oxanosine monophosphate is a covalent inhibitor of inosine 5'-monophosphate dehydrogenase
Chem. Res. Toxicol.
32
456-466
2019
Cryptosporidium parvum, Tritrichomonas foetus, Campylobacter jejuni (A0A2R4D3F6), Bacillus anthracis (A0A6L8P2U9), Homo sapiens (P12268)
Sahu, N.U.; Purushothaman, G.; Thiruvenkatam, V.; Kharkar, P.S.
Design, synthesis, and biological evaluation of Helicobacter pylori inosine 5'-monophosphate dehydrogenase (HpIMPDH) inhibitors
Drug Dev. Res.
80
125-132
2019
Helicobacter pylori, Homo sapiens (P12268), Homo sapiens
Johnson, M.C.; Kollman, J.M.
Cryo-EM structures demonstrate human IMPDH2 filament assembly tunes allosteric regulation
eLife
9
e53243
2020
Homo sapiens (P12268), Homo sapiens
Kofuji, S.; Sasaki, A.T.
GTP metabolic reprogramming by IMPDH2 unlocking cancer cells fuelling mechanism
J. Biochem.
168
319-328
2020
Homo sapiens (P12268)
Shah, C.P.; Kharkar, P.S.
Newer human inosine 5-monophosphate dehydrogenase 2 (hIMPDH2) inhibitors as potential anticancer agents
J. Enzyme Inhib. Med. Chem.
33
972-977
2018
Homo sapiens (P12268), Homo sapiens
Fernandez-Justel, D.; Nunez, R.; Martin-Benito, J.; Jimeno, D.; Gonzalez-Lopez, A.; Soriano, E.M.; Revuelta, J.L.; Buey, R.M.
A nucleotide-dependent conformational switch controls the polymerization of human IMP dehydrogenases to modulate their catalytic activity
J. Mol. Biol.
431
956-969
2019
Homo sapiens (P12268), Homo sapiens
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