Information on EC 1.1.1.205 - IMP dehydrogenase

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY
1.1.1.205
-
RECOMMENDED NAME
GeneOntology No.
IMP dehydrogenase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
IMP + NAD+ + H2O = XMP + NADH + H+
show the reaction diagram
enzyme acts on the hydroxyl group of the hydrated derivative of the substrate, ordered bi-bi mechanism; IMP binds first, followed by NAD+, NADH dissociates from the ternary complex first, then XMP is released
-
IMP + NAD+ + H2O = XMP + NADH + H+
show the reaction diagram
IMP and K+ can bind randomly to the free enzyme, while NAD+ does not react unless K+ or both K+ and IMP are present on the enzyme; mechanism is partially random
-
IMP + NAD+ + H2O = XMP + NADH + H+
show the reaction diagram
mechanism is partially random
-
IMP + NAD+ + H2O = XMP + NADH + H+
show the reaction diagram
enzyme acts on the hydroxyl group of the hydrated derivative of the substrate, ordered bi-bi mechanism
-
IMP + NAD+ + H2O = XMP + NADH + H+
show the reaction diagram
IMP binds first, XMP is released last; ordered sequential mechanism
-
IMP + NAD+ + H2O = XMP + NADH + H+
show the reaction diagram
ordered sequential mechanism
-
IMP + NAD+ + H2O = XMP + NADH + H+
show the reaction diagram
ordered sequential mechanism; sequential addition of IMP, NAD+ and K+
-
IMP + NAD+ + H2O = XMP + NADH + H+
show the reaction diagram
substrate binding and catalytic reaction mechanism, Cys319 is the catalytic residue, NAD+ promotes the nucleophilic attack of Cys319 on IMP
-
IMP + NAD+ + H2O = XMP + NADH + H+
show the reaction diagram
covalent enzyme reaction intermediate, hydrolysis of enzyme-XMP is rate-limiting and requires the adoption of the closed conformation, Arg418 is involved in the reaction mechanism as catalytic base, Thr321 is involved in both hydride transfer and hydrolysis
-
IMP + NAD+ + H2O = XMP + NADH + H+
show the reaction diagram
Arg418 is involved in the reaction mechanism as catalytic base
-
IMP + NAD+ + H2O = XMP + NADH + H+
show the reaction diagram
reaction and kinetic mechanism, an Arg residue is involved in catalysis as general base
-
IMP + NAD+ + H2O = XMP + NADH + H+
show the reaction diagram
reaction and kinetic mechanism, an Arg residue is involved in catalysis as general base, Cys319-linked covalent enzyme intermediate E-XMP
-
IMP + NAD+ + H2O = XMP + NADH + H+
show the reaction diagram
reaction mechanism
Q59Q46
IMP + NAD+ + H2O = XMP + NADH + H+
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
adenosine nucleotides degradation I
-
Biosynthesis of secondary metabolites
-
Drug metabolism - other enzymes
-
guanosine ribonucleotides de novo biosynthesis
-
Metabolic pathways
-
Purine metabolism
-
urate biosynthesis/inosine 5'-phosphate degradation
-
SYSTEMATIC NAME
IUBMB Comments
IMP:NAD+ oxidoreductase
The enzyme acts on the hydroxy group of the hydrated derivative of the substrate.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
dehydrogenase, inosinate
-
-
-
-
EC 1.2.1.14
-
-
formerly
-
IMP dehydrogenase
-
-
-
-
IMP oxidoreductase
-
-
-
-
IMP oxidoreductase
-
-
IMP:NAD+ oxidoreductase
-
-
IMPD
-
-
-
-
IMPDH
-
-
-
-
IMPDH
P49058
-
IMPDH
P12268, P20839
-
IMPDH
P21620
-
IMPDH
Q12658
-
IMPDH
P42851
-
IMPDH
Streptococcus suis 2
-
-
-
IMPDH
Q4VRV8
-
IMPDH
P50097
-
IMPDH
P50098
-
IMPDH II
-
-
IMPDH II
P12268
-
IMPDH-1
-
-
IMPDH-S
Q4VRV6
-
IMPDH1
-
-
IMPDH1
P20839
-
IMPDH2
P12268
-
inosinate dehydrogenase
-
-
-
-
inosinate dehydrogenase
-
-
inosine 5' monophosphate dehydrogenase
P12268
-
inosine 5'-monophosphate dehydrogenase
-
-
-
-
inosine 5'-monophosphate dehydrogenase
-
-
inosine 5'-monophosphate dehydrogenase
P49058
-
inosine 5'-monophosphate dehydrogenase
-
-
inosine 5'-monophosphate dehydrogenase
-
-
inosine 5'-monophosphate dehydrogenase
Q8T6T2
-
inosine 5'-monophosphate dehydrogenase
-
-
inosine 5'-monophosphate dehydrogenase
-
-
inosine 5'-monophosphate dehydrogenase
-
-
inosine 5'-monophosphate dehydrogenase
-
-
inosine 5'-monophosphate dehydrogenase
P12268, P20839
-
inosine 5'-monophosphate dehydrogenase
P21620
-
inosine 5'-monophosphate dehydrogenase
-
-
inosine 5'-monophosphate dehydrogenase
-
-
inosine 5'-monophosphate dehydrogenase
Q12658
-
inosine 5'-monophosphate dehydrogenase
-
-
inosine 5'-monophosphate dehydrogenase
-
-
inosine 5'-monophosphate dehydrogenase
-
-
inosine 5'-monophosphate dehydrogenase
-
-
inosine 5'-monophosphate dehydrogenase
P0C0H6
-
inosine 5'-monophosphate dehydrogenase
-
-
inosine 5'-monophosphate dehydrogenase
-
-
inosine 5'-monophosphate dehydrogenase
P50097
-
inosine 5'-monophosphate dehydrogenase
P50098
-
inosine 5'-monophosphate dehydrogenase 2
-
-
inosine 5'-phosphate dehydrogenase
-
-
inosine 5-monophosphate dehydrogenase
-
-
inosine 5-monophosphate dehydrogenase
-
-
inosine 5-monophosphate dehydrogenase
Streptococcus suis 2
-
-
-
inosine 5-monophosphate dehydrogenase type I
-
-
inosine 5 -monophosphate dehydrogenase
-
-
inosine monophosphate dehydrogenase
-
-
-
-
inosine monophosphate dehydrogenase
-
-
inosine monophosphate dehydrogenase
P12268, P20839
-
inosine monophosphate dehydrogenase
-
-
inosine monophosphate dehydrogenase
-
-
inosine monophosphate oxidoreductase
-
-
-
-
inosine monophosphate oxidoreductase
-
-
inosine-5'-monophosphate dehydrogenase
-
-
inosine-5'-phosphate dehydrogenase
-
-
-
-
inosinic acid 5-monophosphate dehydrogenase
-
-
inosinic acid dehydrogenase
-
-
-
-
Raspberry protein
-
-
-
-
SOI12
-
-
-
-
Superoxide-inducible protein 12
-
-
-
-
type 1 inosine monophosphate
-
-
type 2 inosine monophosphate dehydrogenase
-
-
CAS REGISTRY NUMBER
COMMENTARY
9028-93-7
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
JCM 2152 and ts-4
-
-
Manually annotated by BRENDA team
M strain
-
-
Manually annotated by BRENDA team
strain NA7821 and NA6128
-
-
Manually annotated by BRENDA team
Bacillus subtilis M
M strain
-
-
Manually annotated by BRENDA team
Bacillus subtilis NA7821
strain NA7821 and NA6128
-
-
Manually annotated by BRENDA team
strain CAI4, gene IMH3
Uniprot
Manually annotated by BRENDA team
Candida albicans CAI4
strain CAI4, gene IMH3
Uniprot
Manually annotated by BRENDA team
vero cell-line infected with vaccina virus and parainfluenza virus type 3 strain C243
-
-
Manually annotated by BRENDA team
chinese hamster
-
-
Manually annotated by BRENDA team
Chinese hamster type 2
-
-
Manually annotated by BRENDA team
chinese hamster, MPA resistant VM2 variant cells
-
-
Manually annotated by BRENDA team
hamster type 2
-
-
Manually annotated by BRENDA team
MMRL2651, subtype naturally resistant to inhibition by mycophenolic acid
UniProt
Manually annotated by BRENDA team
Cryptococcus neoformans H99
-
-
-
Manually annotated by BRENDA team
; wild type and guaA mutants
-
-
Manually annotated by BRENDA team
derepressed mutant
-
-
Manually annotated by BRENDA team
guaA strain PL 1068
-
-
Manually annotated by BRENDA team
chicken
-
-
Manually annotated by BRENDA team
IMPDH 1
UniProt
Manually annotated by BRENDA team
IMPDH 2
UniProt
Manually annotated by BRENDA team
IMPDH II
-
-
Manually annotated by BRENDA team
IMPDH type II
-
-
Manually annotated by BRENDA team
IMPDH1
UniProt
Manually annotated by BRENDA team
IMPDH2
UniProt
Manually annotated by BRENDA team
isoform IMPDH 1
UniProt
Manually annotated by BRENDA team
isoform IMPDH 2
UniProt
Manually annotated by BRENDA team
isoform IMPDH1
UniProt
Manually annotated by BRENDA team
isoform IMPDH2
UniProt
Manually annotated by BRENDA team
isoforms IMPDH1 and IMPDH2
-
-
Manually annotated by BRENDA team
isozyme IMPDH II
-
-
Manually annotated by BRENDA team
isozyme IMPDH2
-
-
Manually annotated by BRENDA team
mutants of type II; type II
-
-
Manually annotated by BRENDA team
patients with kidney transplantation
-
-
Manually annotated by BRENDA team
renal transplant patients
-
-
Manually annotated by BRENDA team
stable kidney transplant recipients
-
-
Manually annotated by BRENDA team
thiopurine-treated patients with inflammatory bowel disease
-
-
Manually annotated by BRENDA team
type 1 enzyme, retinal-specific isoforms IMPDH1(546) and IMPDH1(595) and canonical isoform IMPDH1(514)
-
-
Manually annotated by BRENDA team
type I and type II
-
-
Manually annotated by BRENDA team
type I and type II isozymes
-
-
Manually annotated by BRENDA team
type I isozyme
UniProt
Manually annotated by BRENDA team
type II
UniProt
Manually annotated by BRENDA team
type II IMPDH isozyme
-
-
Manually annotated by BRENDA team
type II isozyme
-
-
Manually annotated by BRENDA team
strain MPA100
-
-
Manually annotated by BRENDA team
Leishmania donovani MPA100
strain MPA100
-
-
Manually annotated by BRENDA team
IMPDH type II
-
-
Manually annotated by BRENDA team
IMPDH2
UniProt
Manually annotated by BRENDA team
strains CDC1551 and H37Rv
-
-
Manually annotated by BRENDA team
no activity in Giardia lamblia
-
-
-
Manually annotated by BRENDA team
no activity in Trichomonas vaginalis
-
-
-
Manually annotated by BRENDA team
Parainfluenza virus
type 3, strain C243, propagated in Vero cells
-
-
Manually annotated by BRENDA team
var. Canners' Perfection
-
-
Manually annotated by BRENDA team
; hepatoma 3924A
-
-
Manually annotated by BRENDA team
hepatoma
-
-
Manually annotated by BRENDA team
hepatoma 3924A
-
-
Manually annotated by BRENDA team
Yoshida sarcoma ascites cells
-
-
Manually annotated by BRENDA team
type 2 strain
-
-
Manually annotated by BRENDA team
Streptococcus suis 2
type 2 strain
-
-
Manually annotated by BRENDA team
large splicing variant IMPDH; strains RH and RHDELTATHX, opportunistic apicomplexan parasite, two splicing variants, a short and a large one
SwissProt
Manually annotated by BRENDA team
short splicing variant IMPDH-S; strains RH and RHDELTATHX, opportunistiuc apicomplexan parasite, two splicing variants, a short and a large one
Q4VRV6
SwissProt
Manually annotated by BRENDA team
wild type and mutants
-
-
Manually annotated by BRENDA team
strain Elstree, propagated in Vero cells
-
-
Manually annotated by BRENDA team
Vaccinia virus Elstree
strain Elstree, propagated in Vero cells
-
-
Manually annotated by BRENDA team
Walp., infected with Rhizobium strain CB756
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
malfunction
-
a guanine-prototrophic Escherichia coli strain, MP101, is constructed with the cystathionine beta-synthase subdomain deleted from the chromosomal gene for IMPDH. The ATP content is substantially elevated in mutant strain MP101 whereas the GTP content is slighty reduced. The activities of IMPDH, adenylosuccinate synthetase and GMP reductase are 2 to 3fold lower in MP101 crude extracts compared with wild-type strain. Results of a comparative analysis of the purine nucleotide pools, fluxes and turnover rates in the mutant and wild-type strains, indicate that the cystathionine beta-synthase subdomain of IMPDH plays an important role in the regulation of purine nucleotide metabolism
malfunction
-
mice that are homozygotic knockouts for the gene that encodes the type 2 isozyme die in early embryonic stages, despite presumptive expression of a functional type 1 isozyme and purine salvage enzymes
metabolism
P12268, P20839
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; 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
-
IMPDH activity is required for differentiation of preadipocytes into mature, lipid-laden adipocytes and maintenance of adipose tissue mass
physiological function
-
mutations in the CBS subdomain of IMPDH1 account for 2-3% of autosomal dominant retinitis pigmentosa
physiological function
-
the Bateman domain of IMPDH is a negative trans-regulator of adenylate nucleotide synthesis, whereby this role is independent of the catalytic function of IMPDH in the de novo GMP biosynthesis
physiological function
-
is a key enzyme in the biosynthesis of purine nucleotides
physiological function
-
is a key enzyme in the biosynthesis of purine nucleotides; 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
-
is a key enzyme in the biosynthesis of purine nucleotides
physiological function
-
is a key enzyme in the biosynthesis of purine nucleotides. Loss of both alleles of the type 2 gene results in very early embryonic lethality. Type I enzymatic activity appears not to be essential for normal mouse development or fertility
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
-
IMPDH is recruited to transcription complex through serine 2 phosphorylation of RNA polymerase II C-terminal domain. Subunit Imd2 genetically interacts with Ctk1 kinase. IMPDH is recruited to elongating RNA polymerase II only when serine 2 of the C-terminal domain is phosphorylated by Ctk1 kinase. Loss of Imd2 has little effect on the association of most elongation factors with RNA polymerase II. In cells lacking Imd2 or all the essential IMPDHs in the presence of minimal guanine, a defect in the association of Ctk1 kinase with the promoter region is seen
physiological function
F1DBB2
heterologous expression of IMP dehydrogenase gene mpaF dramatically increases mycophenolic acid resistance in Aspergillus nidulans, which does not produce mycophenolic acid.The growth of an Aspergillus nidulans strain expressing mpaF is only marginally affected by mycophenolic acid at concentrations as high as 200 microg/ml
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
5'-amino-5'-deoxyinosine 5'-N-phosphate + NAD+ + H2O
5'-amino-5'-deoxyxanthosine 5'-N-phosphate + NADH
show the reaction diagram
-
-
-
-
?
5'-mercapto-5'-deoxyinosine 5'-S-phosphate + NAD+ + H2O
5'-mercapto-5'-deoxyxanthosine 5'-phosphate + NADH
show the reaction diagram
-
-
-
-
?
6-thioinosine 5'-phosphate + NAD+ + H2O
6-thioxanthosine 5'-phosphate + NADH
show the reaction diagram
-
-
-
-
?
IMP + NAD+ + H2O
XMP + NADH + H+
show the reaction diagram
P42851, -
-
-
-
?
inosine + NAD+ + H2O
xanthosine + NADH
show the reaction diagram
-
8% of the rate with inosine 5'-phosphate
-
-
?
inosine 5'-diphosphate + NAD+ + H2O
xanthosine 5'-diphosphate + NADH
show the reaction diagram
-
-
-
-
?
inosine 5'-diphosphate + NAD+ + H2O
xanthosine 5'-diphosphate + NADH + H+
show the reaction diagram
-
-
-
-
?
inosine 5'-diphosphate + NAD+ + H2O
xanthosine 5'-diphosphate + NADH + H+
show the reaction diagram
-
-
-
-
?
inosine 5'-diphosphate + NAD+ + H2O
xanthosine 5'-diphosphate + NADH + H+
show the reaction diagram
-, Q81W29
-
-
-
?
inosine 5'-diphosphate + NAD+ + H2O
xanthosine 5'-diphosphate + NADH + H+
show the reaction diagram
-, I3WTS0
-
-
-
?
inosine 5'-diphosphate + NAD+ + H2O
xanthosine 5'-diphosphate + NADH + H+
show the reaction diagram
Q387Q3, -
-
xanthosine 5'-diphosphate is the only product
-
?
inosine 5'-phosphate + 3-acetylpyridine adenine dinucleotide + H2O
xanthosine 5'-phosphate + reduced 3-acetylpyridine adenine dinucleotide
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + acetylpyridine adenine dinucleotide + H2O
xanthosine 5'-phosphate + reduced acetylpyridine adenine dinucleotide
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + NAD+
xanthosine 5'-phosphate + NADH + H+
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + NAD+
xanthosine 5'-phosphate + NADH + H+
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + NAD+
xanthosine 5'-phosphate + NADH + H+
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + NAD+
xanthosine 5'-phosphate + NADH + H+
show the reaction diagram
P12268, P20839
-
-
-
?
inosine 5'-phosphate + NAD+
xanthosine 5'-phosphate + NADH + H+
show the reaction diagram
P24547
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
-
-
-
ir
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
-
-
-
-
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
-
-
-
ir
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
-
-
-
-
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
-
-
-
ir
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
P12268
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
P20839
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
-
-
-
ir
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
-
-
-
r
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
-
-
-
-
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
-
-
-
ir
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
-
-
-
-
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
Q59Q46
-
-
-
r
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
-
-
-
r
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
Q4VRV6, Q4VRV8, -
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
Parainfluenza virus
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
enzyme linked to proliferation and malignancy
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
obligatory step in biosynthesis of nucleic acid guanine
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
subdomain of the enzyme is not required for catalytic activity
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
IMP oxidation is the predominant metabolic route leading to ureide synthesis
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
rate-limiting step of the de novo guanine nucleotide biosynthesis
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
rate-limiting step of the de novo guanine nucleotide biosynthesis
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
rate-limiting step of the de novo guanine nucleotide biosynthesis
-
-
ir
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
rate-limiting step of the de novo guanine nucleotide biosynthesis
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
rate-limiting step of the de novo guanine nucleotide biosynthesis
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
Vaccinia virus, Parainfluenza virus
-
rate-limiting step of the de novo guanine nucleotide biosynthesis, pathway overview
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
the enzyme is important for the synthesis of guanine nucleotides
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
P20839
the enzyme performs the rate-limiting step in guanine nucleotide biosynthesis
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
the reaction is irreversible over the range of pH 5.5 to pH 8.8, step in guanylic acid biosynthesis, the reaction is irreversible over the range of pH 5.5 to pH 8.8
-
-
ir
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
enzyme is highly specific for both inosine 5'-phosphate and NAD+
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
Vaccinia virus Elstree
-
-, rate-limiting step of the de novo guanine nucleotide biosynthesis, pathway overview
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
Bacillus subtilis M
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
Bacillus subtilis NA7821
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
Leishmania donovani MPA100
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH + H+
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH + H+
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH + H+
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH + H+
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH + H+
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH + H+
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH + H+
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH + H+
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH + H+
show the reaction diagram
P0C0H6, -
-
-
-
-
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH + H+
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH + H+
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH + H+
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH + H+
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH + H+
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH + H+
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH + H+
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH + H+
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH + H+
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH + H+
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH + H+
show the reaction diagram
P20839
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH + H+
show the reaction diagram
P50097
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH + H+
show the reaction diagram
Q8T6T2
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH + H+
show the reaction diagram
P21620
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH + H+
show the reaction diagram
P50098
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH + H+
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH + H+
show the reaction diagram
Q12658
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH + H+
show the reaction diagram
P49058
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH + H+
show the reaction diagram
-
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
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH + H+
show the reaction diagram
-
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
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH + H+
show the reaction diagram
Streptococcus suis 2
-
-
-
-
?
inosine 5'-phosphorothioate + NAD+ + H2O
xanthosine 5'-phosphorothioate + NADH
show the reaction diagram
-
-
-
-
?
inosine 5'-triphosphate + NAD+ + H2O
xanthosine 5'-triphosphate + NADH
show the reaction diagram
-
-
-
-
?
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
?
-
P20839
enzyme mutations are involved in autosomal dominant retinitis pigmentosa, pathological mechanism, overview
-
-
-
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
?
-
Q4VRV6, Q4VRV8, -
the parasite damages fetuses in utero and threatens immunocompromized individuals
-
-
-
additional information
?
-
P20839
ssDNA and RNA binding of wild-type and mutant IMPDH1s
-
-
-
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
?
-
-
the CBS subdomain of IMPDH coordinately regulates the adenine and guanine nucleotide pool
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
IMP + NAD+ + H2O
XMP + NADH + H+
show the reaction diagram
P42851, -
-
-
-
?
inosine 5'-diphosphate + NAD+ + H2O
xanthosine 5'-diphosphate + NADH + H+
show the reaction diagram
-, I3WTS0
-
-
-
?
inosine 5'-diphosphate + NAD+ + H2O
xanthosine 5'-diphosphate + NADH + H+
show the reaction diagram
Q387Q3, -
-
xanthosine 5'-diphosphate is the only product
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
-
-
-
ir
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
-
-
-
r
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
Q59Q46
-
-
-
r
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
-
-
-
r
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
Q4VRV6, Q4VRV8, -
-
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
enzyme linked to proliferation and malignancy
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
obligatory step in biosynthesis of nucleic acid guanine
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
subdomain of the enzyme is not required for catalytic activity
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
IMP oxidation is the predominant metabolic route leading to ureide synthesis
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
rate-limiting step of the de novo guanine nucleotide biosynthesis
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
rate-limiting step of the de novo guanine nucleotide biosynthesis
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
rate-limiting step of the de novo guanine nucleotide biosynthesis
-
-
ir
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
rate-limiting step of the de novo guanine nucleotide biosynthesis
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
rate-limiting step of the de novo guanine nucleotide biosynthesis
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
Vaccinia virus, Parainfluenza virus
-
rate-limiting step of the de novo guanine nucleotide biosynthesis, pathway overview
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
the enzyme is important for the synthesis of guanine nucleotides
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
P20839
the enzyme performs the rate-limiting step in guanine nucleotide biosynthesis
-
-
?
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
-
the reaction is irreversible over the range of pH 5.5 to pH 8.8, step in guanylic acid biosynthesis
-
-
ir
inosine 5'-phosphate + NAD+ + H2O
xanthosine 5'-phosphate + NADH
show the reaction diagram
Vaccinia virus Elstree
-
rate-limiting step of the de novo guanine nucleotide biosynthesis, pathway 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
?
-
P20839
enzyme mutations are involved in autosomal dominant retinitis pigmentosa, pathological mechanism, overview
-
-
-
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
?
-
Q4VRV6, Q4VRV8, -
the parasite damages fetuses in utero and threatens immunocompromized individuals
-
-
-
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
3-acetylpyridine adenine dinucleotide
-
-
NAD+
Chlorocebus aethiops, Parainfluenza virus
-
-
NAD+
-
B-sided stereospecificity: 2-3H of IMP is transferred to pro-S position of carbon atom C-4 of the nicotinamide ring in NAD+
NAD+
-
NAD+ can not be replaced by NADP+
NAD+
-
; preferred cofactor, NADP+ shows poor activity, less that 10% compared to NAD+
NAD+
Q4VRV6, Q4VRV8, -
;
NAD+
-
NAD+ promotes the nucleophilic attack of Cys319 on IMP, the NAD+ site may be an exploitable target for the design of antimicrobial drugs
NAD+
-
dependent on
NAD+
-
dependent on; dependent on
NAD+
P12268, P20839
comparison between the NAD+ binding sites of human IMPDHs and Mycobacterium tuberculosis IMPDH; comparison between the NAD+ binding sites of human IMPDHs and Mycobacterium tuberculosis IMPDH
NAD+
-
comparison between the NAD+ binding-sites of human IMPDHs and Mycobacterium tuberculosis IMPDH
NADP+
-
reduction less than 10% of that with NAD+
thiazole-4-carboxamide adenine dinucleotide
-
-
thionicotinamide-NAD+
-
5% as effective as NAD+
acetylpyridine-NAD+
-
60% as effective as NAD+
additional information
-
acetylpyridine adenine dinucleotide
-
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 ACCESSION NO.
COMMENTARY
LITERATURE
Cs+
P49058
activates
Cs+
-
activates
K+
-
requirement of 0.1 M for maximal activity
K+
-
monovalent cation required for maximal activity
K+
-
activates, Km: 1.6 mM, the activation is competitively inhibited by Mg2+; activation; K+ activation is inhibited by Mg2+
K+
-
full activity in presence of K+
K+
-
activation; maximum activity at 33-66 mM KCl
K+
-
activation
K+
-
0.1 M; activation
K+
-
activation
K+
-
requirement, maximal activity at 20 mM
K+
-
strong activation, the K+ site is observed at the subunit interface, the activation is linked to NAD+
K+
-
enhances inosine 5'-phosphate bound at a stoichiometry of four sites per tetramer and the affinity of the type 2 isozyme by 2fold
K+
P49058
activates
K+
-
activates
Na+
-
can partially replace K+ in activation
Na+
-
can partially replace K+ in activation
Na+
-
no effect
Na+
-
activates type 2 isozyme
Na+
-
activates
Na+
P50097
activates
NH4+
-
required
NH4+
-
K+ can be partially replaced by NH4+
NH4+
-
no activation
NH4+
-
activation
NH4+
-
K+ can be partially replaced by NH4+
NH4+
-
activation
NH4+
-
activates type 2 isozyme
NH4+
P49058
activates
Rb+
-
activates type 2 isozyme
Rb+
-
activates
Tl+
-
activation, maximal activity at 5 mM
Tl+
-
activates
K+
P50097
activates
additional information
-
no activation by NH4+
additional information
-
influence of various metal ions on enzyme activity
additional information
-
influence of various metal ions on enzyme activity
additional information
-
100-800 mM K+ does not affect the R418A mutant activity
additional information
-
inosine 5'-phosphate binding is not altered by K+
additional information
-
Na+ has no effect on activity
additional information
-
Li+ has no effect on activity of IMPDH2
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(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-[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]prop-2-enamide
-
isozyme IMPDH II IC50: 28 nM
(2E)-3-furan-2-yl-N-[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]prop-2-enamide
-
;
(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
(2S)-2-[(1-naphthyl)amino]-N-[2-(pyridin-4-yl)-1,3-benzoxazol-5-yl]propanamide
-
competitive versus NAD+
(2S)-2-[(3,4-dichlorophenyl)amino]-N-[2-(pyridin-4-yl)-1,3-benzoxazol-5-yl]propanamide
-
competitive versus NAD+, displays excellent IMPDH inhibitory activity and moderate stability in mouse liver microsomes
(4E)-6-(4,6-dihydroxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enoic acid
P12268, P20839
derivative of mycophenolic acid. IC50 value for K562 cells proliferation 8.2 microM; derivative of mycophenolic acid. IC50 value for K562 cells proliferation 8.2 microM
(4E)-6-[4-(acetyloxy)-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl]-4-methylhex-4-enoic acid
P12268, P20839
derivative of mycophenolic acid. IC50 value for K562 cells proliferation 0.59 microM; 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
P12268, P20839
derivative of mycophenolic acid. IC50 value for K562 cells proliferation 2.1 microM; derivative of mycophenolic acid. IC50 value for K562 cells proliferation 2.1 microM
(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 inhibiton of histone deacetylase and K562 cell proliferation
([[(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
1,4-dimethyl-6-nitro-2H-cyclopenta[d]pyridazine
-
;
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-(2-[3-[(1E)-N-hydroxyethanimidoyl]phenyl]propan-2-yl)-3-quinolin-7-ylurea
-
displays high potency against Cryptosporidium parvum IMPDH, more than 1000fold selectivity versus human IMPDH type 2 and good stability in mouse liver microsomes
1-(3-methylphenyl)-3-[4-(1,3-oxazol-5-yl)phenyl]urea
-
isozyme IMPDH II IC50: 640 nM
1-(4-chloro-5-nitrocyclohexa-1,5-dien-1-yl)-3-(2-[3-[(1E)-N-hydroxyethanimidoyl]phenyl]propan-2-yl)urea
-
displays high potency against Cryptosporidium parvum IMPDH, more than 1000fold selectivity versus human IMPDH type 2 and good stability in mouse liver microsomes
-
1-(benzyloxy)-3-(3-pyridin-4-yl-1H-indol-6-yl)urea
-
;
1-methyl-6-[(5-phenyl-1,3-oxazol-2-yl)amino]-1H-indole-3-carbonitrile
-
;
1-phenylsulfonylindol-3-yl boronic acid
-
-
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-[2-[3-(prop-1-en-2-yl)phenyl]propan-2-yl]-3-quinolin-7-ylurea
-
displays high potency against Cryptosporidium parvum IMPDH, more than 1000fold selectivity versus human IMPDH type 2 and good stability in mouse liver microsomes
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
14,16-dihydroxy-3,8-dimethyl-3,4,5,6,9,10-hexahydro-1H-2-benzoxacyclotetradecine-1,7(8H)-dione
P12268, P20839
inhibition of leukemia K562 cells proliferation, IC50 of 71.3 microM
1H-naphtho[2,3-d]imidazol-2-ylmethyl 4-aminobenzoate
-
binds in the nicotinamide subsite and does not interact with ADP
1H-naphtho[2,3-d]imidazol-2-ylmethyl 4-aminobenzoate
-
-
1H-naphtho[2,3-d]imidazol-2-ylmethyl 4-aminobenzoate
-
not inhibitory to wild-type
1H-naphtho[2,3-d]imidazol-2-ylmethyl 4-aminobenzoate
-
-
2'-Deoxy-ATP
-
18% inhibition at 0.5 mM
2'-deoxy-GDP
-
12% inhibition at 0.5 mM
2'-deoxy-GTP
-
21% inhibition at 0.5 mM
2'-methylthiazole-4-carboxamide adenine dinucleotide
-
noncompetitive inhibition, less cytotoxic against K562 tumor cells
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-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-amino-oxazole-cyanoindoles
-
-
-
2-benzyl-7-methoxy-6-(1,3-oxazol-5-yl)quinolin-4(1H)-one
-
isozyme IMPDH II IC50: 180 nM
2-beta-D-ribofuranosylthiazole-4-carboxamide
-
NSC 286193, RTC
2-beta-D-ribofuranosylthiazole-4-carboxamide 5'-phosphate
-
RTC monophosphate
2-cyano-1-[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]-3-phenylguanidine
-
isozyme IMPDH II IC50: 240 nM
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
P12268, P20839
inhibition of leukemia K562 cells proliferation, IC50 of 4.0 microM; 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-mercaptoethanol
-
inhibits above 2 mM
2-methyl-3-(pyrid-4-yl)indole
-
IC50: 343 nM
2-tert-butyl-7-methoxy-6-(1,3-oxazol-5-yl)quinolin-4(1H)-one
-
isozyme IMPDH II IC50: 0.01 mM
2-[(3,4-dichlorophenyl)amino]-N-[2-(pyridin-4-yl)-1,3-benzoxazol-5-yl]propanamide
-
racemic variant, competitive versus NAD+. Compound displays good antiparasitic activity in a Toxoplasma gondii strain that relies on Cryptosporidium parvum IMPDH, EC50 20 nM. No toxicity is observed against four mammalian cells lines
-
2-[(3-ethyl-4-oxo-3,4-dihydrothieno[3,2-d]pyrimidin-2-yl)sulfanyl]-N-(4-methoxyphenyl)acetamide
-
antagonizes ADP binding
2-[(3-ethyl-4-oxo-3,4-dihydrothieno[3,2-d]pyrimidin-2-yl)sulfanyl]-N-(4-methoxyphenyl)acetamide
-
-
2-[(3-ethyl-4-oxo-3,4-dihydrothieno[3,2-d]pyrimidin-2-yl)sulfanyl]-N-(4-methoxyphenyl)acetamide
-
not inhibitory to wild-type
2-[(3-ethyl-4-oxo-3,4-dihydrothieno[3,2-d]pyrimidin-2-yl)sulfanyl]-N-(4-methoxyphenyl)acetamide
-
-
2-[2-(Z)-fluorovinyl]-inosine 5'-phosphate
-
is a time-dependent inactivator
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
-
;
2264A
-
inhibits lymphocyte proliferation; inhibits lymphocyte proliferation
2264B
-
inhibits lymphocyte proliferation; inhibits lymphocyte proliferation
3'-methylthiazole-4-carboxamide adenine dinucleotide
-
noncompetitive inhibition, less cytotoxic against K562 tumor cells
3-(1H-naphtho[2,3-d]imidazol-2-yl)propyl 4-aminobenzoate
-
-
3-(1H-naphtho[2,3-d]imidazol-2-yl)propyl 4-aminobenzoate
-
not inhibitory to wild-type
3-(1H-naphtho[2,3-d]imidazol-2-yl)propyl 4-aminobenzoate
-
-
3-(pyrid-4-yl)indole
-
-
3-carbamoylindole
-
-
3-cyanoindole
-
inhibits isozyme IMPDH II at 0.03 mM
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-formyl-1-methylindole
-
-
3-formylindole
-
-
3-hydrogenkwadaphnin
-
;
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-methoxy-4-(oxazol-5-yl)aniline
-
-
3-phenyl quinolone derivatives
-
several, isozyme IMPDH II IC50: 5-160 nM, overview
-
4-pyridylindole
-
IC50: 0.00115 mM
4-[(1R)-1-[1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl]ethoxy]quinoline 1-oxide
-, Q81W29
-
4-[(1R)-1-[1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl]ethoxy]quinoline 1-oxide
-
-
4-[[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]amino]-6-phenyl-1,3,5-triazin-2-ol
-
;
5'-thio-IMP
-
competitive inhibitor
5,5'-dithiobis(2-nitrobenzoate)
-
-
5-bromoisoquinolin-6-amine
-
;
5-chloro-1,4-dimethyl-2H-cyclopenta[d]pyridazine-6-carbonitrile
-
;
6,6'-oxydi(1,4-dihydroquinoxaline-2,3-dione)
-
binds in the nicotinamide subsite and does not interact with ADP
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
P12268, P20839
;
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
P12268, P20839
;
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
-
uncompetitive versus IMP
6-Chloro-9-beta-D-ribofuranosylpurine 5 '-phosphate
-
50% inactivation after 90 min at 0.00012 mM Cl-IMP
6-Chloro-9-beta-D-ribofuranosylpurine 5 '-phosphate
-
covalent modification of the enzyme, total inactivation after 15 min at 0.01 mg/ml Cl-IMP, activity can be restored with 2-mercaptoethanol
6-Chloro-9-beta-D-ribofuranosylpurine 5 '-phosphate
-
-
6-Chloro-9-beta-D-ribofuranosylpurine 5 '-phosphate
-
acts at the IMP binding site
6-chloroinosine 5'-phosphate
-
-
6-chloroinosine 5'-phosphate
-
;
6-Chloropurine
-
irreversible inhibitor
6-Chloropurine ribonucleoside 5'-phosphate
-
inosine 5'-phosphate and guanosine 5'-phosphate retard inactivation
6-Chloropurine ribonucleoside 5'-phosphate
-
-
6-mercaptopurine ribonucleotide
-
-
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-thioinosine 5'-phosphate
-
complete inactivation after 10 min preincubation at a concentration of 0.001 mM; in absence of glutathione
6-thioinosine 5'-phosphate
-
in absence of glutathione
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-6-[(2E)-4-methoxy-3-methylbut-2-en-1-yl]-4-methyl-2-benzofuran-1(3H)-one
-
isozyme IMPDH II IC50: 273 nM
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)quinolin-4(1H)-one
-
isozyme IMPDH II IC50: 300 nM
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
P12268, P20839
inhibition of leukemia K562 cells proliferation, IC50 of 71.3 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
P12268, P20839
homology modeling; homology modeling
ADP
Q59Q46
multiple inhibition with tiazofurin, competitive versus NAD+
ADP
P50097
binds in the adenosine portion, tiazofurin and ADP are strongly synergistic inhibitors, a conformational change occurs upon the binding of one inhibitor that increases the affinity of the second inhibitor
allopurinol ribonucleotide
-
-
AMP
-
; competitive
AMP
-
20% inhibition at high concentrations
ATP
-
at high concentration of IMP and KCl
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; induces caspase-independent apoptosis in multiple myeloma cell lines and displays antiproliferative activity against both androgen-dependent and androgen-independent prostate cancer cell lines
benzamide riboside
-
NAD+ binding site inhibitor
benzamide riboside
-
-
benzamide riboside
-
displays skeletal muscle toxicity in preclinical trials, which limits its utility; displays skeletal muscle toxicity in preclinical trials, which limits its utility
benzamide riboside
-
inhibitory activity is higher than tiazofurin and lower than selenazofurin; inhibitory activity is higher than tiazofurin and lower than selenazofurin
beta-difluoromethylene-tiazofurin
-
;
beta-methylene thiazole 4-carboxamide adenine dinucleotide
-
i.e. beta-Me-TAD or CH2-TAD
beta-methylene thiazole 4-carboxamide adenine dinucleotide
-
i.e. beta-Me-TAD
beta-methylene-TAD
-
noncompetitive inhibition
beta-methylene-thiazole-4-carboxamide adenine dinucleotide
-
i.e. beta-Me-TAD, enzyme binding structure analysis, the enzyme active site loop is ordered in this complex, and the catalytic Cys319 is 3.6 A from IMP, in the same plane as the hypoxanthine ring, the active site loop forms hydrogen bonds to the carboxamide of beta-Me-TAD, overview
beta-methylene-thiazole-4-carboxyamide-adenine dinucleotide
-
-
beta-methylene-tiazofurin
-
;
blastadin 11
-
;
BMS-337197
-
isozyme IMPDH II IC50: 16 nM
BMS-337197
-
i.e. BMS-337197
BMS-337197
-
-
BMS-337197
-
IC50: 0.0082 mM
BMS-337197
-
is a potent IMPDH inhibitor, shows in vivo activity for inhibition of antibody production in mice
BMS-337197
-
is a potent IMPDH inhibitor, shows in vivo activity for inhibition of antibody production in the adjuvant-induced arthritis model in rats
C2-mycophenolic adenine dinucleotide
-
methylenephosphophosphonate analogue of mycophenolic adenine dinucleotide
C2-mycophenolic adenine dinucleotide
-
-
C4-mycophenolic adenine dinucleotide
-
methylenephosphophosphonate analogue of mycophenolic adenine dinucleotide
Ca2+
-
29% inactivation in the presence of 0.1M K+
Ca2+
-
competitive inhibition with respect to both K+ and NAD+
CH2-SAD
Q4VRV6, Q4VRV8, -
i.e. 4-carboxamido-2-beta-D-ribofuranosylselenazolyl adenosine methylenediphosphonic acid, an adenine dinucleotide analogue nonhydrolyzable beta-methylene derivative
CH2-TAD
Q4VRV6, Q4VRV8, -
i.e. 4-carboxamido-2-beta-D-ribofuranosylthiazolyl adenosine methylenediphosphonic acid, an adenine dinucleotide analogue nonhydrolyzable beta-methylene derivative
chlorogenic acid
P24547
0.1 mM, 30% inhibition
CMP
-
25% inhibition at 0.6 mM
curcumin
-
significantly reduces the level of GTP and reduces the rate of cell growth
curcumin
P24547
0.1 mM, 68% inhibition, both competitive and uncompetitive
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 [(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
dithioerythrol
-
inhibits above 1 mM
eicosadienoic acid
-
competitive to inosine 5'-phosphate
eicosadienoic acid
-
competitive inhibitor versus IMPDH; competitive inhibitor versus IMPDH
Ellagic acid
P24547
0.1 mM, 27% inhibition
epigallocatechin gallate
P24547
0.1 mM, 47% inhibition
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
ethyl 9-oxo-9,10-dihydroacridine-1-carboxylate
-
;
Fe3+
-
11% inhibition at 1 nM
-
GDP
-
45% inhibition at 0.6 mM
glutathione
-
above 4 mM
GMP
-
competitive with respect to IMP
GMP
-
competitive with respect to IMP and non competitive with respect to NAD+
GMP
-
feedback inhibitor; feed-back inhibitor eliciting 'allosteric' kinetics of the enzyme, determination of the GMP binding site
GMP
-
competitive, 58% inhibition at 0.5 mM
GMP
-
competitive with respect to IMP, non competitive with respect to NAD+ and K+
GMP
-
55% inhibition at 0.6 mM
GMP
-
; competitive
GMP
-
competitive with respect to IMP
GMP
-
competitive with respect to IMP
GMP
-
; weak and competitive inhibition, strong binding, dissociation by 3 M urea
GMP
-
competitive with respect to IMP
GTP
-
45% inhibition at 0.6 mM
halicyclamine A
-
;
helenalin
-
;
HgCl2
-
complete inactivation at 0.5 mM
imidazo[4,5-e][1,4]diazapine
-
-
imidazo[4,5-e][1,4]diazapine
-
fat base nucleotide, inosine 5'-phosphate but not NAD+ protects against inhibition
imidazo[4,5-e][1,4]diazapine
-
fat base nucleotide, inosine 5'-phosphate but not NAD+ protects against inhibition; fat base nucleotide, inosine 5'-phosphate but not NAD+ protects against inhibition
Inosine
-
very weak, non-competitive
Inosine 5'-methylphosphonate
-
very weak, non-competitive
inosine 5'-phosphate
Q4VRV6, Q4VRV8, -
-
Inosine 5'-phosphite
-
very weak, non-competitive
Inosine 5'-phosphofluoridate
-
very weak, non-competitive
iodoacetamide
-
-
iodoacetate
-
-
iodoacetate
-
98% inhibition at 10 mM
Li+
-
competitive to K+
Li+
-
inhibits stimulatory effect of K+
Li+
-
competitive inhibition with respect to both K+ and NAD+
linoleic acid
-
-
linoleic acid
-
;
merimepodib
-
has immunosuppressive activity; has immunosuppressive activity
methyl (4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enoate
P12268, P20839
derivative of mycophenolic acid. IC50 value for K562 cells proliferation 0.73 microM; derivative of mycophenolic acid. IC50 value for K562 cells proliferation 0.73 microM
methyl 3-methyl-2-oxo-1,2-dihydroquinoline-4-carboxylate
-
antagonizes ADP binding
methyl 3-methyl-2-oxo-1,2-dihydroquinoline-4-carboxylate
-
-
methyl 3-methyl-2-oxo-1,2-dihydroquinoline-4-carboxylate
-
not inhibitory to wild-type
methyl 3-methyl-2-oxo-1,2-dihydroquinoline-4-carboxylate
-
-
methyl methanethiosulfonate
-
-
Mg2+
-
inhibits K+ activation
Mg2+
-
inhibits K+ activation
Mg2+
-
inhibits K+ activation
Mg2+
-
competitive inhibition with respect to both K+ and NAD+
mizobirine 5'-monophosphate
-
-
mizoribine
-
-
mizoribine
-
;
mizoribine
P21620
-
mizoribine
P50097
-
mizoribine
P50098
-
mizoribine 5'-monophosphate
Q387Q3, -
-
mizoribine 5'-phosphate
-
complexes the enzyme
mizoribine 5'-phosphate
Q59Q46
competitive versus NAD+, slow tight-binding, the mutant A251T is 20fold more sesitive
mycophenolate mofetil
-
NAD+ binding site inhibitor
mycophenolate mofetil
-
prodrug of mycophenolic acid, treatment of diet-induced obese mice with mycophenolate mofetil for 28 days does not affect food intake or lean body mass but reduces body fat content (by 36%), adipocyte size and number and the appearance of hepatic steatosis
mycophenolate mofetil
-
-
mycophenolic 2-ethyladenosin-5'-yl-difluoromethylenebis(phosphonate)
P12268, P20839
potent, sub-micromolar inhibitor of leukemia K562 cells proliferation, IC50 of 0.45 microM; potent, sub-micromolar inhibitor of leukemia K562 cells proliferation, IC50 of 0.45 microM
mycophenolic 2-ethyladenosin-5'-yl-methylenebis(phosphonate)
P12268, P20839
inhibition of leukemia K562 cells proliferation, IC50 of 1.0 microM; inhibition of leukemia K562 cells proliferation, IC50 of 1.0 microM
Mycophenolic acid
-
50% inhibition at 0.0003 mM, reversible by guanine
Mycophenolic acid
-
mixed type inhibition
Mycophenolic acid
-
-
Mycophenolic acid
-
50% inhibition at 0.00025 mM, human plasma or serum reduces the inhibition
Mycophenolic acid
-
mutants have increased Ki for MPA
Mycophenolic acid
-
uncompetitive
Mycophenolic acid
-
uncompetitive with respect to IMP and NAD+
Mycophenolic acid
-
type II enzme is 4.8fold more sensitive than type I
Mycophenolic acid
-
50% inhibition at 0.024 mM
Mycophenolic acid
Q4VRV6, Q4VRV8, -
uncompetitive to NAD+
Mycophenolic acid
-
i.e. MPA, slight inhibition, microbial IMPDHs differ from mammalian enzymes in their lower affinity for inhibitors such as mycophenolic acid and thiazole-4-carboxamide adenine dinucleotide, part of this resistance is determined by the coupling between nicotinamide and adenosine subsites in the NAD+ binding site that is postulated to involve an active site flap
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
-
isozyme IMPDH II IC50: 15 nM
Mycophenolic acid
-
potent, uncompetitive, reversible, inhibits both isozymes, prodrug is mycophenolate mofetil, isozyme IMPDH II IC50: 14 nM
Mycophenolic acid
-
potent, uncompetitive, reversible, inhibits both isozymes, prodrug is mycophenolate mofetil
Mycophenolic acid
-
isozyme IMPDH II IC50: 11 nM, potent, uncompetitive inhibition, immunosuppressive drug, prodrug is mycophenolate mofetil
Mycophenolic acid
-
enzyme inhibition by mycophenolic acid impairs maturation and function of dendritic cells
Mycophenolic acid
-
traps the reaction intermediate E-XMP, the human enzyme is sensitive to the inhibtior due to its open dehydrogenase conformation
Mycophenolic acid
Q59Q46
inhibition of the wild-type enzyme uncompetitively versus NAD+, the mutant A251T enzyme is 4fold more resistant to mycophenolic acid
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
-
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
-
exerts immunosuppression through inhibition of the enzyme in lymphocytes, inhibitory potency in vivo, overview, prodrug is mycophenolate mofetil
Mycophenolic acid
-
comparison with inhibiton of histone deacetylase and K562 cell proliferation
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
-
IMD2 imparts mycophenolic acid resistance due to A253S as a critical amino acid substitution
Mycophenolic acid
-
in 3T3-L1 preadipocytes inhibition of IMPDH with mycophenolic acid reduces intracellular GTP levels by 60% (p <0.05) and blocks adipogenesis. Co-treatment with guanosine restores GTP levels and adipogenesis
Mycophenolic acid
-
-
Mycophenolic acid
-
uncompetitive inhibition
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
-
-
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; 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
E3P6S3
subtype MMRL2651 of Cryptococcus gattii is naturally resistant to inhibition by mycophenolic acid
Mycophenolic acid
-
-
Mycophenolic acid
-
;
Mycophenolic acid
P12268, P20839
inhibition of leukemia K562 cells proliferation, IC50 of 7.7 microM; inhibition of leukemia K562 cells proliferation, IC50 of 7.7 microM
Mycophenolic acid
-, Q81W29
noncompetitive with regard to inosine monophosphate and NAD+
Mycophenolic acid
-, I3WTS0
inhibitory to enzyme, also inhibits growth of Babesia gibsoni cells. The treated parasite cultures have predominantly single Babesia cells as opposed to untreated cells that have both single and dividing forms as observed on day two
Mycophenolic acid
-
-
mycophenolic acid glucuronide
-
80% inhibition at 0.2 mM, human plasma or serum reduces the inhibition
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
mycophenolic acid-acyl-glucuronide
-
cross-reactivity by mycophenolic acid is less than 5%, thus interference is expected to be clinically irrelevant
mycophenolic adenine dinucleotide
-
-
mycophenolic hydroxamic acid
-
comparison with inhibiton of histone deacetylase and K562 cell proliferation
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-(2,3-dichlorophenyl)-2-[2-(1,3-thiazol-2-yl)-1H-benzimidazol-1-yl]acetamide
-
poor inhibition of human IMPDH2
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-(4-bromophenyl)-2-[2-(1,3-thiazol-2-yl)-1H-benzimidazol-1-yl]acetamide
-
crystallization data. Poor inhibition of human IMPDH2
N-(4-chlorophenyl)-2-phenoxypropanamide
-
antagonizes ADP binding
N-(4-methoxyphenyl)-2-(3-methyl-4-oxo-3,4-dihydrophthalazin-1-yl)acetamide
-
binds in the nicotinamide subsite and does not interact with ADP
N-(4-methoxyphenyl)-2-(3-methyl-4-oxo-3,4-dihydrophthalazin-1-yl)acetamide
-
-
N-(4-methoxyphenyl)-2-(3-methyl-4-oxo-3,4-dihydrophthalazin-1-yl)acetamide
-
not inhibitory to wild-type
N-(4-methoxyphenyl)-2-(3-methyl-4-oxo-3,4-dihydrophthalazin-1-yl)acetamide
-
-
N-(4-methoxyphenyl)-2-naphthalen-1-ylacetamide
-
binds in the nicotinamide subsite and does not interact with ADP
N-(4-methoxyphenyl)-2-[2-(1,3-thiazol-4-yl)-1H-benzimidazol-1-yl]acetamide
-
binds in the nicotinamide subsite and does not interact with ADP
N-(4-methoxyphenyl)-2-[2-(1,3-thiazol-4-yl)-1H-benzimidazol-1-yl]acetamide
-
-
N-(4-methoxyphenyl)-2-[2-(1,3-thiazol-4-yl)-1H-benzimidazol-1-yl]acetamide
-
not inhibitory to wild-type
N-(4-methoxyphenyl)-2-[2-(1,3-thiazol-4-yl)-1H-benzimidazol-1-yl]acetamide
-
-
N-(5-phenyl-1,3-oxazol-2-yl)isoquinolin-6-amine
-
;
N-(naphthalen-2-yl)-2-[2-(1,3-thiazol-2-yl)-1H-benzimidazol-1-yl]acetamide
-
poor inhibition of human IMPDH2
N-(naphthalen-2-yl)-2-[2-(1,3-thiazol-4-yl)-1H-benzimidazol-1-yl]acetamide
-
poor inhibition of human IMPDH2
N-(naphthalen-2-yl)-2-[2-(pyridin-2-yl)-1H-benzimidazol-1-yl]acetamide
-, Q81W29
-
N-(naphthalen-2-yl)-2-[2-(pyridin-2-yl)-1H-benzimidazol-1-yl]acetamide
-
-
N-(naphthalen-2-yl)-2-[2-(pyridin-2-yl)-5,6-dihydro-1H-benzimidazol-1-yl]acetamide
-
-
N-(naphthalen-2-yl)-2-[2-(pyridin-2-yl)-5,6-dihydro-1H-benzimidazol-1-yl]acetamide
-
not inhibitory to wild-type
N-(naphthalen-2-yl)-2-[2-(pyridin-2-yl)-5,6-dihydro-1H-benzimidazol-1-yl]acetamide
-
-
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-ethylmaleimide
-
100% inhibition at 1 mM
N-hydroxy-N'-[3-methoxy-4-(1,3-oxazol-2-yl)phenyl]octanediamide
-
comparison with inhibiton 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-[(Z)-(pyridin-3-ylimino)methyl]-2,3-dihydro-1,4-benzodioxine-2-carboxamide
-
-
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]-2-(3-methyl-4-oxo-3,4-dihydrophthalazin-1-yl)acetamide
-
noncompetitive with respect to NAD+, displays submicromolar activity in a Toxoplasma gondii model of Cryptosporidium parvum infection and displays good stability in mouse liver microsome. No antiparasitic activity is observed in mouse with once per day oral dosing of 250 mg/kg for 7 days
Na+
-
competitive inhibition with respect to both K+ and NAD+
NAD+
-
substrate inhibition at high concentration
NAD+
-
50% inhibition at 0.62 mM
NAD+
-
substrate inhibition at high concentration
NAD+
-
44% inhibition at 1.5 M
NAD+
-
substrate inhibition at high concentration
NAD+
Q4VRV6, Q4VRV8, -
-
NAD+
-
at high concentration, inhibition of canonical isoform. No inhibition of retinal-specific isoforms
NAD+
P12268, P20839
;
NAD+
Q387Q3, -
substrate inhibition
NADH
-
; mixed inhibition type versus inosine 5'-phosphate and NAD+
NADH
-
; uncompetitive versus inosine 5'-phosphate and mixed inhibition type versus NAD+
NADH
-
non competitive
NADH
-
poor inhibitor, product inhibition, non competitive
NADH
-
non competitive with respect to NAD+
NADH
-
non competitive with respect to K+, IMP and NAD
NADPH
-
50% inhibition at 0.14 mM
NH4+
-
25% inhibition at 2.12 M
nicotinic acid
-
inhibitory analog of NAD+, non-competitive with respect to IMP and K+
p-chloromercuribenzoate
-
inhibition can be restored by addition of DTT
p-chloromercuribenzoate
-
100% inhibition at 0.021 mM
p-chloromercuribenzoate
-
-
p-hydroxymercuribenzoate
-
97% inactivation at 1 mM
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-(thiazofurin-5'-yl)-P2-(adenosyl-5'-yl)-alpha,beta-methylene diphosphate
-
-
P1-(tiazofurin-5'-yl)-P2-(2-aminoadenosin-5'-yl) diphosphate
-
comparison with inhibiton of alcohol dehydrogenase, malate dehydrogenase, lactate dehydrogenase and K562 cell proliferation
P1-(tiazofurin-5'-yl)-P2-(2-ethyladenosin-5'-yl) diphosphate
-
comparison with inhibiton of alcohol dehydrogenase, malate dehydrogenase, lactate dehydrogenase and K562 cell proliferation
P1-(tiazofurin-5'-yl)-P2-(2-ethynyladenosin-5'-yl) diphosphate
-
comparison with inhibiton of alcohol dehydrogenase, malate dehydrogenase, lactate dehydrogenase and K562 cell proliferation
P1-(tiazofurin-5'-yl)-P2-(2-iodoadenosin-5'-yl) diphosphate
-
comparison with inhibiton of alcohol dehydrogenase, malate dehydrogenase, lactate dehydrogenase and K562 cell proliferation
P1-(tiazofurin-5'-yl)-P2-(2-phenyladenosin-5'-yl) diphosphate
-
comparison with inhibiton of alcohol dehydrogenase, malate dehydrogenase, lactate dehydrogenase and K562 cell proliferation
P1-(tiazofurin-5'-yl)-P2-(adenosin-5'-yl) diphosphate
-
comparison with inhibiton 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)
-
-
pellynic acid
-
;
phenyl N'-cyano-N-(3-[cyano[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]carbamimidamido]benzyl)imidocarbamate
-
;
phosphate
-
mixed inhibition kinetics
quinazolinedione derivatives
-
several derivatives, synthesis and inhibitory values, overview
-
quinazolinethione derivatives
-
several derivatives, synthesis and inhibitory values, overview
-
ribavirin
Parainfluenza virus, Vaccinia virus
-
potent competitive inhibition, shows anti-viral activity in vivo, detailed overview
ribavirin
-
-
ribavirin
-
;
ribavirin
P50097
-
ribavirin 5'-monophosphate
-
-
ribavirin 5'-monophosphate
-
-
ribavirin 5'-monophosphate
-
competitive with respect to IMP
ribavirin 5'-monophosphate
-
-
ribavirin 5'-monophosphate
Q387Q3, -
-
ribavirin 5'-phosphate
-
-
ribavirin monophosphate
-
;
ribavirin monophosphate
-
-
ribose 5-phosphate
-
non-competitive
SAD
Q4VRV6, Q4VRV8, -
i.e. selenazole-4-carboxamido adenine diphosphonic acid, an adenine dinucleotide analogue
Selenazofurin
-
inhibition (in vivo) by the NAD analog formed intracellularly
Selenazofurin
Parainfluenza virus
-
potent competitive inhibition, shows anti-viral activity in vivo, detailed overview, a complete reversal of the antiviral activity of selenazofurin was obtained by addition of guanosine and selenazofurin at varying concentrations
Selenazofurin
-
potent competitive inhibition, shows anti-viral activity in vivo, detailed overview
Selenazofurin
P20839
;
selenazole adenine dinucleotide
-
-
selenazole-4-carboxyamide-adenine dinucleotide
-
;
Sesquiterpene lactones
-
a class of anti-neoplastic drugs, overview
-
TAD
Q4VRV6, Q4VRV8, -
i.e. thiazole-4-carboxamide adenine dinucleotide, an adenine dinucleotide analogue
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)
P12268, P20839
inhibition of leukemia K562 cells proliferation, IC50 of 4.7 microM; inhibition of leukemia K562 cells proliferation, IC50 of 4.7 microM
thiazole-4-carboxamide 2-ethyladenine dinucleotide
P12268, P20839
;
thiazole-4-carboxamide adenine dinucleotide
-
inhibition is strong and not reversible by NAD+; thiazole-4-carboxamide adenine dinucleotide acts non competitive
thiazole-4-carboxamide adenine dinucleotide
-
reversible inhibition
thiazole-4-carboxamide adenine dinucleotide
-
-
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, uncompetitive versus inosine 5'-phosphate and mixed inhibition type versus NAD+
thiazole-4-carboxamide adenine dinucleotide
-
-
thiazole-4-carboxamide adenine dinucleotide
-
inhibitory mechanism
thiazole-4-carboxamide adenine dinucleotide
-
uncompetitive with respect to IMP and NAD
thiazole-4-carboxamide adenine dinucleotide
-
i.e. TAD, slight inhibition, microbial IMPDHs differ from mammalian enzymes in their lower affinity for inhibitors such as mycophenolic acid and thiazole-4-carboxamide adenine dinucleotide, part of this resistance is determined by the coupling between nicotinamide and adenosine subsites in the NAD+ binding site that is postulated to involve an active site flap
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
P12268, P20839
inhibition of leukemia K562 cells proliferation, IC50 of 3.7 microM; inhibition of leukemia K562 cells proliferation, IC50 of 3.7 microM
tiazofurin
-
decrease of cell growth
tiazofurin
-
i.e. 2-beta-D-ribofuranosyl-thiazole-4-carboxamide, overview: clinical and molecular impact of inhibition; 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
tiazofurin
-
inhibits cell proliferation of hepatoma cells, overview
tiazofurin
Chlorocebus aethiops, Parainfluenza virus, Vaccinia virus
-
-
tiazofurin
-
noncompetitive inhibition, cytotoxic against K562 tumor cells
tiazofurin
Q59Q46
multiple inhibition with ADP, noncompetitive versus NAD+
tiazofurin
P50097
binds in the nicotinamide portion of the dinucleotide site, tiazofurin and ADP are strongly synergistic inhibitors, a conformational change occurs upon the binding of one inhibitor that increases the affinity of the second inhibitor
tiazofurin
P20839
;
TMP
-
25% inhibition at 0.6 mM
UMP
-
25% inhibition at 0.6 mM
Urea
-
inactive at 3 M but regains activity after dialysis
VX-148
-
isozyme IMPDH II IC50: 6 nM
VX-148
-
has immunosuppressive activity; has immunosuppressive activity
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
VX-497
-
isozyme IMPDH II IC50: 11 nM
xanthosine 5'-phosphate
-
competitive inhibition
xanthosine 5'-phosphate
-
competitive inhibition
xanthosine 5'-phosphate
-
; competitive versus inosine 5'-phosphate but noncompetitive versus NAD+
xanthosine 5'-phosphate
-
39% competitive, inhibition at 0.5 mM
xanthosine 5'-phosphate
-
non-competitive with respect to NAD
xanthosine 5'-phosphate
-
competitive with respect to IMP, non competitive with respect to NAD and K+
xanthosine 5'-phosphate
-
product inhibitor
xanthosine 5'-phosphate
-
-
xanthosine 5'-phosphate
-
competitive with respect to IMP
xanthosine 5'-phosphate
-
-
xanthosine 5'-phosphate
-
-
xanthosine 5'-phosphate
-
competitive with respect to IMP
xanthosine 5'-phosphate
-
competitive with respect to IMP
xanthosine 5'-phosphate
-
-
xanthosine 5'-phosphate
-, Q81W29
competitive with regard to inosine monophosphate
Zn2+
-
complete inhibition at 1 nM
[(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
[(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
additional information
-
dinucleotide analogs of NAD
-
additional information
-
inhibition by products and antimetabolites
-
additional information
-
-
-
additional information
-
-
-
additional information
-
inhibition by purine and pyrimidine compounds
-
additional information
-
the enzyme is not affected by allantoin, allantoic acid, uric acid, inosine, xanthosine, and xanthosine 5'-phosphate
-
additional information
-
-
-
additional information
-
mycophenolic acid and it's nuclear variants
-
additional information
-
-
-
additional information
-
6-ethoxycarbonyl-3,3-disubstituted-1,5-diazabicyclo[3.1.0.]hexane-2,4-diones inhibit type II enzyme
-
additional information
Q4VRV6, Q4VRV8, -
no inhibition by tiazofurin and seleno-thiazofurin
-
additional information
-
no enzyme inhibition by nucleic acids
-
additional information
-
structural basis of the drug selectivity, overview
-
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
-
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
-
inhibitor development and synthesis, overview
-
additional information
-
inhibition of the enzyme in K562 cells sensitizes the before resistant cells to methotrexate
-
additional information
-
retinal isoforms do not bind significant fractions of a random pool of oligonucleotides
-
additional information
-
not inhibitory: linoelaidic acid, methyl linoleate, cis-9-octadecen-1-ol
-
additional information
-
IMPDH2 interacts with protein kinase B/Akt via its plekstrin homology domain, the resulting phosphorylation reduces activity
-
additional information
P50097
becomes resistant to IMPDH inhibitors by rearranging its purine salvage pathways to rely on xanthine instead of hypoxanthine
-
additional information
-
mycophenolic acid-phenyl-glucuronide has no effect
-
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
-
1,2,3-triazole containing ether IMPDH inhibitors, small alkyl group on the alpha-position of the ether is required, with the (R)-enantiomer significantly more active than the (S)-enantiomer. Electron-withdrawing groups in the 3- and/or 4-positions of the pendent phenyl ring are best, and conversion of the quinoline containing inhibitors to quinoline-N-oxides retains inhibitory activity both in the presence and absence of bovine serum albumin
-
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
P12268, P20839
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; 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
P24547
not inhibitory: resveratrol, genistein, eugenol, gingerol, naringenin, naringin, caffeic acid, morin, kaempferol, hesperidin, rosmarinic acid
-
additional information
-
compounds are not inhibitory to Escherichia coli, Tritrichomonas foetus, and Leishmania donovani IMPDH. Susceptible enzymes are defined by structural motif A165/Y358, Cryptosporidium parvum numbering
-
additional information
-
tacrolimus, cyclosporine and prednisolone do not affect IMPDH activity
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
ATP
-
30% activation at 0.8 mM
ATP
-
allosteric activator of the enzyme
Bovine serum albumin
-
final concentration of 0.05% stimulates 50%
-
Cs+
-, Q81W29
36% of the activity with K+
cysteine
-
cysteine or glutathione required
dimethyl sulfoxide
-, Q81W29
up to 15-20% increase IMP dehydrogenase activity
glutathione
-
level for maximum activity: 2-4 mM
glutathione
-
removal of glutathione from the reaction mixture causes 35% loss of acitivity
glutathione
-
cysteine or glutathione required
K+
-
the K+ dependence of kcat value derives from the rate of flap closure, which increases by more than 65fold in the presence of K+. When K+ is replaced with a dummy ion, the residues of the K+ binding site relax into ordered secondary structure, creating a barrier to conformational exchange. K+ mobilizes these residues by providing alternate interactions for the main chain carbonyls. So K+ changes the shape of the energy well, shrinking the reaction coordinate by shifting the closed conformation toward the open state
K+
-, Q81W29
optimal activation at 100-150 mM K+
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
Na+
-, Q81W29
less than 1% of the activity with K+
NH4+
-, Q81W29
77% of the activity with K+
Reducing agent
-
effectiveness decreases in the order: dithiothreitol, mercaptoethanol, cyanide, ascorbate
-
Sulfhydryl-reducing agents
-
required for maximal activity
-
Li+
-, Q81W29
less than 1% of the activity with K+
additional information
-
the enzyme is not affected by allantoin, allantoic acid, uric acid, inosine, xanthosine, and xanthosine 5'-phosphate
-
additional information
-
genes IMD2, IMD3 and IMD4 support growth in the absence of guanine
-
additional information
-, Q81W29
strict requirement for a monovalent cation
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.19
-
3-acetylpyridine adenine dinucleotide
-
presence of 100 mM K+, pH 8.0, 25C
0.22
-
3-acetylpyridine adenine dinucleotide
-
absence of K+, pH 8.0, 25C
0.038
-
5'-Amino-5'-deoxyinosine 5'-N-phosphate
-
-
0.013
-
5'-mercapto-5'-deoxyinosine 5'-S-phosphate
-
-
0.02
-
6-thio-IMP
-
pH 8.1
0.19
-
Acetylpyridine adenine dinucleotide
-
-
0.007
-
IMP
-
-
0.012
-
IMP
-
-
0.013
-
IMP
-
-
0.014
-
IMP
-
-
0.0256
-
IMP
-
-
0.0082
-
Inosine 5'-diphosphate
-, I3WTS0
pH 8.0, 25C
0.018
-
Inosine 5'-diphosphate
-, Q81W29
pH 8.0, 22C
0.03
-
Inosine 5'-diphosphate
Q387Q3, -
pH 8.0, 25C
0.0017
-
inosine 5'-phosphate
-
pH 8.0, 25C, recombinant full-length enzyme, in presence of 100 mM KCl
0.0017
-
inosine 5'-phosphate
-
in the presence of 12 mM K+
0.0024
-
inosine 5'-phosphate
-
pH 8.0, 25C, recombinant alphabeta core domain, in absence of 100 mM KCl
0.0026
-
inosine 5'-phosphate
-
pH 8.0, 25C, recombinant full-length enzyme, in absence of 100 mM KCl
0.003
-
inosine 5'-phosphate
-
pH 8.0, 25C, recombinant alphabeta core domain, in presence of 100 mM KCl
0.004
-
inosine 5'-phosphate
-
isoform IMPDH1(514), pH 8.0, 25C
0.00455
-
inosine 5'-phosphate
-
-
0.007
-
inosine 5'-phosphate
P20839
pH 8.0, 37C, recombinant mutant R224P
0.0091
-
inosine 5'-phosphate
-
pH 8.8, 30C
0.0092
-
inosine 5'-phosphate
-
type 2 isozyme, in the presence of 0.39 mM K+
0.01
-
inosine 5'-phosphate
-
mutant D226N of isoform IMPDH1(595), pH 8.0, 25C
0.011
-
inosine 5'-phosphate
P20839
pH 8.0, 37C, recombinant mutant V268I
0.011
-
inosine 5'-phosphate
-
isoform IMPDH1(595), pH 8.0, 25C; mutant D226N of isoform IMPDH1(546), pH 8.0, 25C
0.012
-
inosine 5'-phosphate
P20839
pH 8.0, 37C, recombinant mutant D226N
0.0132
-
inosine 5'-phosphate
-
-
0.014
-
inosine 5'-phosphate
-
type 1 isozyme, in the presence of 0.65 mM K+
0.015
-
inosine 5'-phosphate
-
isoform IMPDH1(546), pH 8.0, 25C
0.017
-
inosine 5'-phosphate
P20839
pH 8.0, 37C, recombinant wild-type enzyme
0.02
-
inosine 5'-phosphate
-
pH 7.5, 22C
0.021
-
inosine 5'-phosphate
-
6-thioinosine 5'-phosphate, constant in pH-range 6.5-8.2, sharp decrease at higher pH
0.029
-
inosine 5'-phosphate
-
in the presence of 25 mM K+
0.029
-
inosine 5'-phosphate
-
-
0.033
-
inosine 5'-phosphate
-
pH 7.5, 25C
0.042
-
inosine 5'-phosphate
-
mutant L263F, 37C, pH 8.0
0.0458
-
inosine 5'-phosphate
-
wild-type, 37C, pH 8.0
0.0509
-
inosine 5'-phosphate
P24547
pH not specified in the publication, temperature not specified in the publication
0.06
-
inosine 5'-phosphate
-
in the presence of 2.8 mM K+
0.062
-
inosine 5'-phosphate
-
-
0.078
-
inosine 5'-phosphate
-
pH 8.0, 25C
1.7
-
inosine 5'-phosphate
-
wild-type, pH 8.0, 25C
7.6
-
inosine 5'-phosphate
-
mutant R322A, pH 8.0, 25C
28
-
inosine 5'-phosphate
-
mutant Q324A, pH 8.0, 25C
31
-
inosine 5'-phosphate
-
mutant E323A, pH 8.0, 25C
0.21
-
Inosine 5'-phosphorothioate
-
-
0.00157
-
NAD+
-
-
0.006
-
NAD+
-
pH 8.0, 25C
0.014
-
NAD+
-
isoform IMPDH1(514), pH 8.0, 25C
0.016
-
NAD+
-
-
0.016
-
NAD+
-
mutant D226N of isoform IMPDH1(595), pH 8.0, 25C
0.0163
-
NAD+
-
wild-type, 37C, pH 8.0
0.018
0.035
NAD+
-
pH 8.8, 30C
0.022
-
NAD+
-
isoform IMPDH1(546), pH 8.0, 25C
0.0227
-
NAD+
-
mutant L263F, 37C, pH 8.0
0.024
-
NAD+
-
mutant D226N of isoform IMPDH1(546), pH 8.0, 25C
0.025
-
NAD+
-
-
0.026
-
NAD+
-
isoform IMPDH1(595), pH 8.0, 25C
0.032
-
NAD+
-
type 2 isozyme, in the presence of 0.39 mM K+
0.042
-
NAD+
-
type 1 isozyme, in the presence of 0.65 mM K+
0.046
-
NAD+
-
-
0.046
-
NAD+
P20839
pH 8.0, 37C, recombinant mutant V268I
0.05
-
NAD+
P20839
pH 8.0, 37C, recombinant mutant D226N
0.056
-
NAD+
P20839
pH 8.0, 37C, recombinant mutant R224P
0.065
-
NAD+
-
-
0.07
-
NAD+
P20839
pH 8.0, 37C, recombinant wild-type enzyme
0.11
-
NAD+
-
pH 8.0, 25C, recombinant alphabeta core domain, in presence of 100 mM KCl
0.12
-
NAD+
-
mutant Q324A, pH 8.0, 25C
0.14
-
NAD+
-
presence of 1 mM K+, pH 8.0, 25C
0.144
-
NAD+
Q4VRV6, Q4VRV8, -
pH 8.0, 37C, recombinant enzyme
0.15
-
NAD+
-
-
0.15
-
NAD+
-
pH 8.0, 25C, recombinant full-length enzyme, in presence of 100 mM KCl
0.15
-
NAD+
-
in the presence of 12 mM K+
0.15
-
NAD+
-
wild-type, pH 8.0, 25C
0.17
-
NAD+
-
-
0.3
-
NAD+
-
mutant E323A, pH 8.0, 25C
0.36
-
NAD+
-, I3WTS0
pH 8.0, 25C
0.39
-
NAD+
-
pH 7.5, 25C
0.55
-
NAD+
-, Q81W29
pH 8.0, 22C
0.91
-
NAD+
-
mutant R322A, pH 8.0, 25C
1.005
-
NAD+
-
pH 8.0, 25C
1.1
-
NAD+
-
pH 8.0, 25C, recombinant full-length enzyme, in absence of 100 mM KCl
1.1
-
NAD+
-
in the presence of 25 mM K+
1.2
-
NAD+
-
pH 8.0, 25C, recombinant alphabeta core domain, in absence of 100 mM KCl
1.3
-
NAD+
Q387Q3, -
pH 8.0, 25C
1.4
-
NAD+
-
absence of K+, pH 8.0, 25C
2
-
NAD+
-
in the presence of 2.8 mM K+
2.4
-
NAD+
-
presence of 1 mM K+, pH 8.0, 25C
2.6
-
NAD+
-
mutant R322E, pH 8.0, 25C
0.59
-
thiazole-4-carboxamide adenine dinucleotide
-
chemically synthesized thiazole-4-carboxamide adenine dinucleotide
0.65
-
thiazole-4-carboxamide adenine dinucleotide
-
enzymatically synthesized thiazole-4-carboxamide adenine dinucleotide
1.03
-
thiazole-4-carboxamide adenine dinucleotide
-
ex vivo thiazole-4-carboxamide adenine dinucleotide
additional information
-
additional information
-
-
-
additional information
-
additional information
-
kinetics; Km over the range of pH 7.3-8.5
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
wild type and mutants of type II
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
overview
-
additional information
-
additional information
-
nucleic acid binding kinetics
-
additional information
-
additional information
-
nucleic acid binding kinetics, recombinant full-length type I isozyme and subdomain
-
additional information
-
additional information
-
nucleic acid binding kinetics, recombinant wild-type and mutant enzyme core domains
-
additional information
-
additional information
P20839
ssDNA binding kinetics of wild-type and mutant IMPDH1s
-
additional information
-
additional information
-
detailed kinetics, pre-steady-state kinetics, mechanistic rate constants, wild-type enzyme and mutant enzymes, overview
-
additional information
-
additional information
-
kinetics, wild-type enzyme and mutant enzymes
-
additional information
-
additional information
-
analysis of microscopic rate constants
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.16
-
3-acetylpyridine adenine dinucleotide
-
absence of K+, pH 8.0, 25C
3
-
3-acetylpyridine adenine dinucleotide
-
presence of 100 mM K+, pH 8.0, 25C
3
-
Acetylpyridine adenine dinucleotide
-
-
0.0233
-
IMP
-
type II
0.03
-
IMP
-
type I
0.28
-
Inosine 5'-diphosphate
Q387Q3, -
pH 8.0, 25C
1.4
-
Inosine 5'-diphosphate
-, Q81W29
pH 8.0, 22C
0.009
-
inosine 5'-phosphate
-
mutant R322E, pH 8.0, 25C
0.17
-
inosine 5'-phosphate
-
mutant L263F, 37C, pH 8.0
0.18
-
inosine 5'-phosphate
-
isoform IMPDH1(595), pH 8.0, 25C
0.22
-
inosine 5'-phosphate
-
isoform IMPDH1(546), pH 8.0, 25C; mutant D226N of isoform IMPDH1(595), pH 8.0, 25C
0.24
-
inosine 5'-phosphate
-
mutant D226N of isoform IMPDH1(546), pH 8.0, 25C
0.31
-
inosine 5'-phosphate
-
isoform IMPDH1(514), pH 8.0, 25C
0.36
-
inosine 5'-phosphate
-
mutant R322A, pH 8.0, 25C
0.43
-
inosine 5'-phosphate
-
mutant Q324A, pH 8.0, 25C
0.53
-
inosine 5'-phosphate
-
pH 8.0, 25C
0.98
-
inosine 5'-phosphate
Q4VRV6, Q4VRV8, -
pH 8.0, 37C, recombinant enzyme
1.1
-
inosine 5'-phosphate
-
mutant E323A, pH 8.0, 25C
1.4
-
inosine 5'-phosphate
-
pH 8.0, 25C, recombinant alphabeta core domain, in presence of 100 mM KCl
1.4
-
inosine 5'-phosphate
-
type 2 isozyme, in the presence of 0.39 mM K+
1.47
-
inosine 5'-phosphate
-
wild-type, 37C, pH 8.0
1.8
-
inosine 5'-phosphate
-
type 1 isozyme, in the presence of 0.65 mM K+
1.9
-
inosine 5'-phosphate
-
pH 8.0, 25C, recombinant full-length enzyme, in presence of 100 mM KCl
1.9
-
inosine 5'-phosphate
-
in the presence of 12 mM K+
1.9
-
inosine 5'-phosphate
-
wild-type, pH 8.0, 25C
2.6
-
inosine 5'-phosphate
-
in the presence of 25 mM K+
3.3
-
inosine 5'-phosphate
-
-
13
-
inosine 5'-phosphate
-
in the presence of 2.8 mM K+
0.0217
-
NAD+
-
type II enzyme
0.025
-
NAD+
-
type I enzyme
0.27
-
NAD+
-
absence of K+, pH 8.0, 25C
0.39
-
NAD+
-
pH 8.0, 25C
0.7
-
NAD+
P20839
pH 8.0, 37C, recombinant mutant D226N
0.8
-
NAD+
P20839
pH 8.0, 37C, recombinant mutant V268I
0.8
-
NAD+
-
presence of 1 mM K+, pH 8.0, 25C
0.9
-
NAD+
P20839
pH 8.0, 37C, recombinant mutant A285T
0.98
-
NAD+
Q4VRV6, Q4VRV8, -
pH 8.0, 37C, recombinant enzyme
1.2
-
NAD+
P20839
pH 8.0, 37C, recombinant wild-type enzyme
1.3
-
NAD+
P20839
pH 8.0, 37C, recombinant mutant R224P
1.4
-
NAD+
-
pH 8.0, 25C, recombinant alphabeta core domain, in presence of 100 mM KCl
1.9
-
NAD+
-
pH 8.0, 25C, recombinant full-length enzyme, in presence of 100 mM KCl
2.6
-
NAD+
-
presence of 1 mM K+, pH 8.0, 25C
24
-
inosine 5'-phosphate
-
-
additional information
-
additional information
-
various substrates
-
additional information
-
additional information
-
overview
-
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
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, 25C
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, 25C
0.0011
-
2'-methylthiazole-4-carboxamide adenine dinucleotide
-
isozyme IMPDH I
0.0014
-
2'-methylthiazole-4-carboxamide adenine dinucleotide
-
isozyme IMPDH II
0.115
-
2-beta-D-ribofuranosylthiazole-4-carboxamide 5'-phosphate
-
pH 7.4, 37C
0.001
-
2-[2-(Z)-fluorovinyl]-inosine 5'-phosphate
-
-
0.00052
-
3'-methylthiazole-4-carboxamide adenine dinucleotide
-
isozyme IMPDH I
0.00066
-
3'-methylthiazole-4-carboxamide adenine dinucleotide
-
isozyme IMPDH II
3.4e-05
-
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
P12268, P20839
pH 8.0, 25C
7.7e-05
-
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
P12268, P20839
pH 8.0, 25C
4.4e-05
-
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
P12268, P20839
pH 8.0, 25C
7e-05
-
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
P12268, P20839
pH 8.0, 25C
0.0015
-
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, 25C
0.078
-
6-chloroinosine 5'-phosphate
-
-
0.26
-
6-Cl-IMP
-
-
0.14
-
6-thio-IMP
-
-
7e-06
-
7-methoxy-6-(1,3-oxazol-5-yl)-2-phenylquinolin-4(1H)-one
-
-
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, 25C
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, 25C
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, 25C
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, 25C
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, 25C
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, 25C
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, 25C
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, 25C
2
5
ADP
-
mutant E323A, pH 8.0, 25C
7
-
ADP
-
mutant Q324A, pH 8.0, 25C
8.8
-
ADP
-
;
16
-
ADP
Q59Q46
pH 8.0, 25C, recombinant mutant A251T
17
-
ADP
-
mutant R322A, pH 8.0, 25C
31
-
ADP
P50097
-
31
-
ADP
-
wild-type, pH 8.0, 25C
34
-
ADP
Q59Q46
pH 8.0, 25C, recombinant wild-type enzyme
50
-
ADP
-
mutant R322E, pH 8.0, 25C
0.282
-
AMP
-
-
0.53
-
AMP
-
-
6e-06
-
AVN944
-
;
0.25
0.33
C2-mycophenolic adenine dinucleotide
-
pH 8.0, 25C
0.38
0.52
C4-mycophenolic adenine dinucleotide
-
pH 8.0, 25C
0.00038
-
CH2-SAD
Q4VRV6, Q4VRV8, -
pH 8.0, 37C, recombinant enzyme
0.00098
-
CH2-TAD
Q4VRV6, Q4VRV8, -
pH 8.0, 37C, recombinant enzyme
0.0997
-
curcumin
P24547
pH not specified in the publication, temperature not specified in the publication
0.027
-
EAD
-
-
0.002
-
EICARMP
-
-
0.016
-
EICARMP
-
-
0.003
-
eicosadienoic acid
-
-
0.0031
-
eicosadienoic acid
-
pH 8.0, 37C
0.038
-
FFAD
-
with inosine 5'-phosphate as substrate
0.056
-
FFAD
-
with inosine 5'-phosphate as substrate
0.05
-
GMP
-
-
0.06
-
GMP
-
; pH 8.8, 30C
0.092
-
GMP
-
-
0.1
-
GMP
-
-
0.21
-
GMP
-
pH 7.5, 25C
1e-06
-
imidazo[4,5-e][1,4]diazapine
-
-
5e-05
-
imidazo[4,5-e][1,4]diazapine
-
IMPDH2
4.5
-
inosine 5'-phosphate
Q4VRV6, Q4VRV8, -
pH 8.0, 37C, recombinant enzyme
7e-06
-
merimepodib
-
;
5e-07
-
mizoribine
-
-
8e-06
-
mizoribine
-
-
0.0033
-
mizoribine 5'-monophosphate
Q387Q3, -
pH 8.0, 25C
1e-08
-
mizoribine 5'-phosphate
Q59Q46
pH 8.0, 25C, recombinant mutant A251T
2e-07
-
mizoribine 5'-phosphate
Q59Q46
pH 8.0, 25C, recombinant wild-type enzyme
0.0005
-
mizoribine monophosphate
-
-
0.0039
-
mizoribine monophosphate
-
type 2 isozyme
0.0082
-
mizoribine monophosphate
-
type 1 isozyme
2e-07
-
Mycophenolic acid
-
-
1.1e-06
-
Mycophenolic acid
Q59Q46
pH 8.0, 25C, recombinant wild-type enzyme
2e-06
-
Mycophenolic acid
-
for the competitive component
4.4e-06
-
Mycophenolic acid
Q59Q46
pH 8.0, 25C, recombinant mutant A251T
7e-06
-
Mycophenolic acid
-
against type II isoform
8e-06
-
Mycophenolic acid
-
for the non-competitive component
9e-06
-
Mycophenolic acid
-
-
1e-05
-
Mycophenolic acid
-
isoform IMPDH2, pH 8.0, 25C
2e-05
-
Mycophenolic acid
-
-
2e-05
-
Mycophenolic acid
-
against IMPDH in general; against IMPDH in general
2.5e-05
-
Mycophenolic acid
-
pH 7.5, 25C
3e-05
-
Mycophenolic acid
Q4VRV6, Q4VRV8, -
pH 8.0, 37C, recombinant enzyme
3.3e-05
-
Mycophenolic acid
-
type I isoform
4e-05
-
Mycophenolic acid
-
isoform IMPDH1, pH 8.0, 25C
5.08e-05
-
Mycophenolic acid
-
in the presence of NAD+
5.77e-05
-
Mycophenolic acid
-
in the presence of inosine 5'-phosphate
0.0011
-
Mycophenolic acid
-
type 1 isozyme
0.0039
-
Mycophenolic acid
-, Q81W29
substrate NAD+, pH 8.0, 22C
0.0048
-
Mycophenolic acid
-, Q81W29
substrate inosine monophosphate, pH 8.0, 22C
0.006
-
Mycophenolic acid
-
type 2 isozyme
0.01
-
Mycophenolic acid
-
isoform IMPDH2, pH 8.0, 25C
0.011
-
Mycophenolic acid
-
wild-type, 37C, pH 8.0
0.0182
-
Mycophenolic acid
-
mutant L263F, 37C, pH 8.0
0.021
-
Mycophenolic acid
-, I3WTS0
pH 8.0, 25C
0.021
-
Mycophenolic acid
Q387Q3, -
pH 8.0, 25C
0.04
-
Mycophenolic acid
-
isoform IMPDH1, pH 8.0, 25C
8
-
Mycophenolic acid
-
-
9
-
Mycophenolic acid
-
-
0.000382
-
mycophenolic acid-acyl-glucuronide
-
in the presence of NAD+
0.000511
-
mycophenolic acid-acyl-glucuronide
-
in the presence of inosine 5'-phosphate
3e-05
-
mycophenolic hydroxamic acid
-
isoform IMPDH2, pH 8.0, 25C
7e-05
-
mycophenolic hydroxamic acid
-
isoform IMPDH1, pH 8.0, 25C
7.1e-05
-
myelophenolic acid
-
at a fixed concentration of 0.5 mM NAD+ and 0.03 mM IMP
-
0.000178
-
myelophenolic acid
-
at a fixed concentration of 0.5 mM NAD+
-
0.00069
-
myelophenolic acid
-
; at a fixed concentration of 0.03 mM IMP
-
0.0017
-
N-hydroxy-N'-[3-methoxy-4-(1,3-oxazol-2-yl)phenyl]octanediamide
-
isoform IMPDH2, pH 8.0, 25C
0.005
-
N-hydroxy-N'-[3-methoxy-4-(1,3-oxazol-2-yl)phenyl]octanediamide
-
isoform IMPDH1, pH 8.0, 25C
3.2e-06
-
N-[4-chloro-3-(trifluoromethyl)phenyl]-2-(3-methyl-4-oxo-3,4-dihydrophthalazin-1-yl)acetamide
-
pH not specified in the publication, temperature not specified in the publication
0.6
-
NAD+
-
absence of K+, pH 8.0, 25C
1
-
NAD+
P20839
pH 8.0, 37C, recombinant mutant R224P
1.5
-
NAD+
-
presence of 1 mM K+, pH 8.0, 25C
2
-
NAD+
P20839
pH 8.0, 37C, recombinant wild-type enzyme
2.9
-
NAD+
-
pH 8.0, 25C, recombinant alphabeta core domain, in presence of 100 mM KCl
3
-
NAD+
Q387Q3, -
pH 8.0, 25C
3.9
-
NAD+
-, Q81W29
pH 8.0, 22C
4
-
NAD+
P20839
pH 8.0, 37C, recombinant mutants D226N and V268I
4.9
-
NAD+
-
presence of 100 mM K+, pH 8.0, 25C
5
-
NAD+
-
pH 8.0, 25C
6.8
-
NAD+
-
pH 8.0, 25C, recombinant full-length enzyme, in presence of 100 mM KCl
0.094
-
NADH
-
-
0.21
-
NADH
-
versus inosine 5'-phosphate
0.23
-
NADH
-
versus inosine 5'-phosphate
0.287
-
NADH
-
versus NAD+
0.38
-
NADH
-
versus NAD+
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, 25C
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, 25C
9.5e-05
-
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
0.0015
-
P1-(thiazofurin-5'-yl)-P2-(adenosyl-5'-yl)-alpha,beta-methylene diphosphate
-
-
0.0016
-
P1-(thiazofurin-5'-yl)-P2-(adenosyl-5'-yl)-alpha,beta-methylene diphosphate
-
-
0.0023
-
P1-(thiazofurin-5'-yl)-P2-(adenosyl-5'-yl)-alpha,beta-methylene diphosphate
-
-
0.0085
-
P1-(thiazofurin-5'-yl)-P2-(adenosyl-5'-yl)-alpha,beta-methylene diphosphate
-
-
7e-06
-
P1-(tiazofurin-5'-yl)-P2-(2-aminoadenosin-5'-yl) diphosphate
-
isoform IMPDH1, pH 8.0, 25C
2.7e-05
-
P1-(tiazofurin-5'-yl)-P2-(2-aminoadenosin-5'-yl) diphosphate
-
isoform IMPDH2, pH 8.0, 25C
1e-06
-
P1-(tiazofurin-5'-yl)-P2-(2-ethyladenosin-5'-yl) diphosphate
-
isoform IMPDH1, pH 8.0, 25C
1.4e-05
-
P1-(tiazofurin-5'-yl)-P2-(2-ethyladenosin-5'-yl) diphosphate
-
isoform IMPDH2, pH 8.0, 25C
1e-05
-
P1-(tiazofurin-5'-yl)-P2-(2-ethynyladenosin-5'-yl) diphosphate
-
isoform IMPDH1, pH 8.0, 25C
4.9e-05
-
P1-(tiazofurin-5'-yl)-P2-(2-ethynyladenosin-5'-yl) diphosphate
-
isoform IMPDH2, pH 8.0, 25C
1.9e-05
-
P1-(tiazofurin-5'-yl)-P2-(2-iodoadenosin-5'-yl) diphosphate
-
isoform IMPDH1, pH 8.0, 25C
8.4e-05
-
P1-(tiazofurin-5'-yl)-P2-(2-iodoadenosin-5'-yl) diphosphate
-
isoform IMPDH2, pH 8.0, 25C
2e-05
-
P1-(tiazofurin-5'-yl)-P2-(2-phenyladenosin-5'-yl) diphosphate
-
isoform IMPDH1, pH 8.0, 25C
0.000143
-
P1-(tiazofurin-5'-yl)-P2-(2-phenyladenosin-5'-yl) diphosphate
-
isoform IMPDH2, pH 8.0, 25C
0.00011
-
P1-(tiazofurin-5'-yl)-P2-(adenosin-5'-yl) diphosphate
-
isoform IMPDH1, pH 8.0, 25C; isoform IMPDH2, pH 8.0, 25C
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, 25C
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, 25C
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, 25C
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, 25C
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, 25C
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, 25C
0.00025
-
ribavirin 5'-monophosphate
-
-
0.00058
-
ribavirin 5'-monophosphate
-
-
0.0008
-
ribavirin 5'-monophosphate
-
-
0.0032
-
ribavirin 5'-monophosphate
Q387Q3, -
pH 8.0, 25C
6.5e-05
-
ribavirin monophosphate
-
-
0.00039
-
ribavirin monophosphate
-
type 2 isozyme
0.00065
-
ribavirin monophosphate
-
type 1 isozyme
0.006
-
ribavirin monophosphate
-
-
0.0018
-
SAD
Q4VRV6, Q4VRV8, -
pH 8.0, 37C, recombinant enzyme
2e-05
-
Selenazofurin
-
with inosine 5'-phosphate as substrate
3e-05
-
Selenazofurin
-
with inosine 5'-phosphate as substrate
0.00058
-
SFAD
-
with inosine 5'-phosphate as substrate
0.0011
-
SFAD
-
with inosine 5'-phosphate as substrate
0.0018
-
TAD
Q4VRV6, Q4VRV8, -
pH 8.0, 37C, recombinant enzyme
0.00043
-
TFAD
-
with inosine 5'-phosphate as substrate
0.0007
-
TFAD
-
with inosine 5'-phosphate as substrate
5.8e-05
-
thiazole-4-carboxamide adenine dinucleotide
-
pH 7.4, 37C
7.5e-05
-
thiazole-4-carboxamide adenine dinucleotide
-
-
0.000123
-
thiazole-4-carboxamide adenine dinucleotide
-
chemically synthesized thiazole-4-carboxamide adenine dinucleotide
0.00019
-
thiazole-4-carboxamide adenine dinucleotide
-
isozyme IMPDH I
0.000226
-
thiazole-4-carboxamide adenine dinucleotide
-
enzymatically synthesized thiazole-4-carboxamide adenine dinucleotide
0.00024
-
thiazole-4-carboxamide adenine dinucleotide
-
isozyme IMPDH II
0.00029
-
thiazole-4-carboxamide adenine dinucleotide
-
versus inosine 5'-phosphate
0.00031
-
thiazole-4-carboxamide adenine dinucleotide
-
versus inosine 5'-phosphate
0.000345
-
thiazole-4-carboxamide adenine dinucleotide
-
ex vivo thiazole-4-carboxamide adenine dinucleotide
0.00058
-
thiazole-4-carboxamide adenine dinucleotide
-
-
0.00073
-
thiazole-4-carboxamide adenine dinucleotide
-
versus NAD+
0.00074
-
thiazole-4-carboxamide adenine dinucleotide
-
versus NAD+
0.0013
-
thiazole-4-carboxamide adenine dinucleotide
-
-
0.00043
-
tiazofurin
-
with inosine 5'-phosphate as substrate
0.0007
-
tiazofurin
-
with inosine 5'-phosphate as substrate
1.3
-
tiazofurin
-
;
1.5
-
tiazofurin
-
-
26
-
tiazofurin
Q59Q46
pH 8.0, 25C, recombinant wild-type enzyme
40
-
tiazofurin
Q59Q46
pH 8.0, 25C, recombinant mutant A251T
50
-
tiazofurin
P50097
-
69
-
tiazofurin
-
wild-type, pH 8.0, 25C
90
-
tiazofurin
-
mutant Q324A, pH 8.0, 25C
91
-
tiazofurin
-
mutant R322A, pH 8.0, 25C
200
-
tiazofurin
-
mutant R322E, pH 8.0, 25C
300
-
tiazofurin
-
mutant E323A, pH 8.0, 25C
6e-06
-
VX-148
-
-
1.4e-05
-
VX-148
-
-
7e-06
-
VX-497
-
type I isoform
1e-05
-
VX-497
-
against type II isoform
0.03
-
xanthosine 5'-phosphate
-
-
0.085
-
xanthosine 5'-phosphate
-
-
0.085
-
xanthosine 5'-phosphate
-
-
0.109
-
xanthosine 5'-phosphate
-
-
0.118
-
xanthosine 5'-phosphate
-
versus inosine 5'-phosphate
0.136
-
xanthosine 5'-phosphate
-
-
0.136
-
xanthosine 5'-phosphate
-
versus inosine 5'-phosphate
0.218
-
xanthosine 5'-phosphate
-, Q81W29
pH 8.0, 22C
0.28
-
xanthosine 5'-phosphate
-
versus NAD+
0.32
-
xanthosine 5'-phosphate
-
versus NAD+
0.026
-
XMP
-
pH 7.5, 25C
0.0115
-
mizoribine monophosphate
-
-
additional information
-
additional information
-
; inhibition kinetics
-
additional information
-
additional information
-
inhibition kinetics; various inhibitors
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
Ki over the range of pH 7.3 to 8.5
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
inhibition kinetics
-
additional information
-
additional information
-
inhibition by purine nucleotides
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
wild type and mutants
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
wild type and mutants
-
additional information
-
additional information
-
multi-inhibitor kinetics
-
additional information
-
additional information
-
inhibition patterns, isozymes I and II
-
additional information
-
additional information
Q59Q46
inhibition kinetics, structure-inhibitory potency relationship, overview
-
additional information
-
additional information
-
mycophenolic acid inhibition kinetics
-
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
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
-
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
-
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
-
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
-
isozyme IMPDH II IC50: 498 nM
9.3e-05
-
(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
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
-
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
-
isozyme IMPDH II IC50: 132 nM
6.8e-05
-
(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
2.4e-05
-
(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
1.3e-05
-
(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
2.8e-05
-
(2E)-3-furan-2-yl-N-[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]prop-2-enamide
-
isozyme IMPDH II IC50: 28 nM
2.8e-05
-
(2E)-3-furan-2-yl-N-[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]prop-2-enamide
-
-
0.002
-
(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
1.4e-05
-
(2S)-2-[(1-naphthyl)amino]-N-[2-(pyridin-4-yl)-1,3-benzoxazol-5-yl]propanamide
-
pH 8.0, 25C
5e-07
-
(2S)-2-[(3,4-dichlorophenyl)amino]-N-[2-(pyridin-4-yl)-1,3-benzoxazol-5-yl]propanamide
-
pH 8.0, 25C
0.00015
-
(4E)-6-(4,6-dihydroxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enoic acid
P12268, P20839
pH 7.4, 37C
0.00017
-
(4E)-6-(4,6-dihydroxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enoic acid
P12268, P20839
pH 7.4, 37C
0.0041
-
(4E)-6-[4-(acetyloxy)-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl]-4-methylhex-4-enoic acid
P12268, P20839
pH 7.4, 37C; pH 7.4, 37C
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
P12268, P20839
pH 7.4, 37C
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
P12268, P20839
pH 7.4, 37C
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
-
isozyme IMPDH II IC50: 246 nM
2.3e-05
-
([[(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
0.0019
-
1,4-dimethyl-6-nitro-2H-cyclopenta[d]pyridazine
-
-
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
-
IC50: 0.094 mM, isozyme IMPDH II
9e-07
-
1-(2-[3-[(1E)-N-hydroxyethanimidoyl]phenyl]propan-2-yl)-3-quinolin-7-ylurea
-
pH 8.0, 25C
0.00064
-
1-(3-methylphenyl)-3-[4-(1,3-oxazol-5-yl)phenyl]urea
-
isozyme IMPDH II IC50: 640 nM
6.6e-07
-
1-(4-chloro-5-nitrocyclohexa-1,5-dien-1-yl)-3-(2-[3-[(1E)-N-hydroxyethanimidoyl]phenyl]propan-2-yl)urea
-
pH 8.0, 25C
-
7.6e-05
-
1-(benzyloxy)-3-(3-pyridin-4-yl-1H-indol-6-yl)urea
-
-
3.3e-05
-
1-methyl-6-[(5-phenyl-1,3-oxazol-2-yl)amino]-1H-indole-3-carbonitrile
-
-
3.5e-05
-
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
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
-
IC50: 948 nM, isozyme IMPDH II
3.5e-05
-
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
8e-07
-
1-[2-[3-(prop-1-en-2-yl)phenyl]propan-2-yl]-3-quinolin-7-ylurea
-
pH 8.0, 25C
4.3e-05
-
1-[3-chloro-4-(1,3-oxazol-5-yl)phenyl]-3-(3-methylphenyl)urea
-
isozyme IMPDH II IC50: 43 nM
1.9e-05
-
1-[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]-3-(3-methylphenyl)urea
-
isozyme IMPDH II IC50: 19 nM
0.0005
-
1-[4-(4-methyl-1,3-oxazol-5-yl)phenyl]-3-(3-methylphenyl)urea
-
isozyme IMPDH II IC50: 500 nM
2e-05
-
14,16-dihydroxy-3,8-dimethyl-3,4,5,6,9,10-hexahydro-1H-2-benzoxacyclotetradecine-1,7(8H)-dione
P12268, P20839
pH 8.0, 25C
0.00022
-
1H-naphtho[2,3-d]imidazol-2-ylmethyl 4-aminobenzoate
-
pH 8.0, 25C
0.0003
-
1H-naphtho[2,3-d]imidazol-2-ylmethyl 4-aminobenzoate
-
pH 8.0, 25C
0.0004
-
1H-naphtho[2,3-d]imidazol-2-ylmethyl 4-aminobenzoate
-
mutant S250A/L444Y, pH 8.0, 25C
0.00055
-
1H-naphtho[2,3-d]imidazol-2-ylmethyl 4-aminobenzoate
-
pH 8.0, 25C
0.0016
-
2-(1,3-oxazol-5-yl)-5-[(5-phenyl-1,3-oxazol-2-yl)amino]phenol
-
isozyme IMPDH II IC50: 0.0016 mM
3e-05
-
2-(1-benzothiophen-3-yl)-6-methoxy-5-(1,3-oxazol-5-yl)-1H-indole-3-carbaldehyde
-
-
0.0002
-
2-(dimethylamino)-7-methoxy-6-(1,3-oxazol-5-yl)quinolin-4(1H)-one
-
isozyme IMPDH II IC50: 200 nM
0.00018
-
2-benzyl-7-methoxy-6-(1,3-oxazol-5-yl)quinolin-4(1H)-one
-
isozyme IMPDH II IC50: 180 nM
0.00024
-
2-cyano-1-[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]-3-phenylguanidine
-
isozyme IMPDH II IC50: 240 nM
7.3e-05
-
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
P12268, P20839
pH 8.0, 25C
9.9e-05
-
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
P12268, P20839
pH 8.0, 25C
3.2e-05
-
2-furan-3-yl-7-methoxy-6-(1,3-oxazol-5-yl)quinolin-4(1H)-one
-
isozyme IMPDH II IC50: 32 nM
4.1e-05
-
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
0.000343
-
2-methyl-3-(pyrid-4-yl)indole
-
IC50: 343 nM
0.01
-
2-tert-butyl-7-methoxy-6-(1,3-oxazol-5-yl)quinolin-4(1H)-one
-
isozyme IMPDH II IC50: 0.01 mM
2e-06
-
2-[(3,4-dichlorophenyl)amino]-N-[2-(pyridin-4-yl)-1,3-benzoxazol-5-yl]propanamide
-
pH 8.0, 25C
-
0.0008
-
2-[(3-ethyl-4-oxo-3,4-dihydrothieno[3,2-d]pyrimidin-2-yl)sulfanyl]-N-(4-methoxyphenyl)acetamide
-
pH 8.0, 25C
0.0011
-
2-[(3-ethyl-4-oxo-3,4-dihydrothieno[3,2-d]pyrimidin-2-yl)sulfanyl]-N-(4-methoxyphenyl)acetamide
-
mutant S250A/L444Y, pH 8.0, 25C
0.0011
-
2-[(3-ethyl-4-oxo-3,4-dihydrothieno[3,2-d]pyrimidin-2-yl)sulfanyl]-N-(4-methoxyphenyl)acetamide
-
pH 8.0, 25C
0.013
-
2-[(3-ethyl-4-oxo-3,4-dihydrothieno[3,2-d]pyrimidin-2-yl)sulfanyl]-N-(4-methoxyphenyl)acetamide
-
pH 8.0, 25C
7e-06
-
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
-
-
0.07
-
2264A
-
-
0.00086
-
3-(1H-naphtho[2,3-d]imidazol-2-yl)propyl 4-aminobenzoate
-
pH 8.0, 25C
0.0009
-
3-(1H-naphtho[2,3-d]imidazol-2-yl)propyl 4-aminobenzoate
-
pH 8.0, 25C
0.001
-
3-(1H-naphtho[2,3-d]imidazol-2-yl)propyl 4-aminobenzoate
-
mutant S250A/L444Y, pH 8.0, 25C
0.0012
-
3-(1H-naphtho[2,3-d]imidazol-2-yl)propyl 4-aminobenzoate
-
pH 8.0, 25C
3.3e-05
0.00042
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
-
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
-
isozyme IMPDH II IC50: 100 nM
2.1e-05
-
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
5e-06
0.00016
3-phenyl quinolone derivatives
-
several, isozyme IMPDH II IC50: 5-160 nM, overview
-
0.00115
-
4-pyridylindole
-
IC50: 0.00115 mM
5.7e-05
-
4-[(1R)-1-[1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl]ethoxy]quinoline 1-oxide
-, Q81W29
pH 8.0, 22C
0.00012
-
4-[(1R)-1-[1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl]ethoxy]quinoline 1-oxide
-
pH 8.0, 22C
1.8e-05
-
4-[[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]amino]-6-phenyl-1,3,5-triazin-2-ol
-
-
0.0005
-
5-bromoisoquinolin-6-amine
-
-
0.00076
-
5-chloro-1,4-dimethyl-2H-cyclopenta[d]pyridazine-6-carbonitrile
-
-
0.000328
-
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
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
-
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
-
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
-
IC50: 0.393 mM, isozyme IMPDH II
9.6e-05
-
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
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
-
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
-
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
-
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
-
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
-
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
-
IC50: 300 nM, isozyme IMPDH II
4.9e-05
-
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
5e-06
-
7-methoxy-2-(3-methylphenyl)-6-(1,3-oxazol-5-yl)quinolin-4(1H)-one
-
-
0.00022
-
7-methoxy-2-(methylamino)-6-(1,3-oxazol-5-yl)quinolin-4(1H)-one
-
isozyme IMPDH II IC50: 220 nM
0.00011
-
7-methoxy-2-methyl-6-(1,3-oxazol-5-yl)quinolin-4(1H)-one
-
isozyme IMPDH II IC50: 110 nM
6.5e-05
-
7-methoxy-3-methyl-6-(1,3-oxazol-5-yl)-2-phenylquinolin-4(1H)-one
-
isozyme IMPDH II IC50: 65 nM
0.000104
-
7-methoxy-3-methyl-6-(1,3-oxazol-5-yl)quinazoline-2,4(1H,3H)-dione
-
IC50: 104 nM, isozyme IMPDH II
0.00021
-
7-methoxy-6-(1,3-oxazol-4-yl)-2-phenylquinolin-4(1H)-one
-
isozyme IMPDH II IC50: 210 nM
3.4e-05
-
7-methoxy-6-(1,3-oxazol-5-yl)-2-(1,3-thiazol-4-yl)quinolin-4(1H)-one
-
isozyme IMPDH II IC50: 34 nM
8e-06
-
7-methoxy-6-(1,3-oxazol-5-yl)-2-phenoxyquinolin-4(1H)-one
-
isozyme IMPDH II IC50: 8 nM
8e-06
-
7-methoxy-6-(1,3-oxazol-5-yl)-2-phenylquinolin-4(1H)-one
-
isozyme IMPDH II IC50: 8 nM
4.3e-05
-
7-methoxy-6-(1,3-oxazol-5-yl)-2-pyridin-2-ylquinolin-4(1H)-one
-
isozyme IMPDH II IC50: 43 nM
7e-05
-
7-methoxy-6-(1,3-oxazol-5-yl)-2-pyridin-3-ylquinolin-4(1H)-one
-
isozyme IMPDH II IC50: 70 nM
4.6e-05
-
7-methoxy-6-(1,3-oxazol-5-yl)-2-pyridin-4-ylquinolin-4(1H)-one
-
isozyme IMPDH II IC50: 46 nM
6.3e-05
-
7-methoxy-6-(1,3-oxazol-5-yl)-2-thiophen-2-ylquinolin-4(1H)-one
-
isozyme IMPDH II IC50: 63 nM
9e-06
-
7-methoxy-6-(1,3-oxazol-5-yl)-2-thiophen-3-ylquinolin-4(1H)-one
-
isozyme IMPDH II IC50: 9 nM
0.000303
-
7-methoxy-6-(1,3-oxazol-5-yl)-2-thioxo-2,3-dihydroquinazolin-4(1H)-one
-
IC50: 303 nM
1.3e-05
-
7-methoxy-6-(1,3-oxazol-5-yl)-3-(2-pyridin-4-ylethyl)-2-thioxo-2,3-dihydroquinazolin-4(1H)-one
-
-
0.0003
-
7-methoxy-6-(1,3-oxazol-5-yl)quinolin-4(1H)-one
-
isozyme IMPDH II IC50: 300 nM
3.7e-05
-
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
P12268, P20839
pH 8.0, 25C
1.6e-05
-
BMS-337197
-
isozyme IMPDH II IC50: 16 nM
0.0082
-
BMS-337197
-
IC50: 0.0082 mM
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
-
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
-
isozyme IMPDH II IC50: 289 nM
0.0161
-
eicosadienoic acid
-
pH 8.0, 37C
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
-
IC50: 0.08 mM, isozyme IMPDH II
0.00073
-
ethyl 9-oxo-9,10-dihydroacridine-1-carboxylate
-
-
0.0014
-
methyl (4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enoate
P12268, P20839
pH 7.4, 37C
0.0015
-
methyl (4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enoate
P12268, P20839
pH 7.4, 37C
0.0009
-
methyl 3-methyl-2-oxo-1,2-dihydroquinoline-4-carboxylate
-
pH 8.0, 25C
0.0015
-
methyl 3-methyl-2-oxo-1,2-dihydroquinoline-4-carboxylate
-
pH 8.0, 25C
0.0018
-
methyl 3-methyl-2-oxo-1,2-dihydroquinoline-4-carboxylate
-
mutant S250A/L444Y, pH 8.0, 25C
0.015
-
methyl 3-methyl-2-oxo-1,2-dihydroquinoline-4-carboxylate
-
pH 8.0, 25C
5e-06
-
mycophenolic 2-ethyladenosin-5'-yl-difluoromethylenebis(phosphonate)
P12268, P20839
pH 8.0, 25C
2.4e-05
-
mycophenolic 2-ethyladenosin-5'-yl-difluoromethylenebis(phosphonate)
P12268, P20839
pH 8.0, 25C
1.6e-05
-
mycophenolic 2-ethyladenosin-5'-yl-methylenebis(phosphonate)
P12268, P20839
pH 8.0, 25C
3.8e-05
-
mycophenolic 2-ethyladenosin-5'-yl-methylenebis(phosphonate)
P12268, P20839
pH 8.0, 25C
7e-06
-
Mycophenolic acid
P12268, P20839
pH 8.0, 25C
1.1e-05
-
Mycophenolic acid
-
isozyme IMPDH II IC50: 11 nM, potent, uncompetitive inhibition, immunosuppressive drug, prodrug is mycophenolate mofetil
1.2e-05
-
Mycophenolic acid
P12268, P20839
pH 7.4, 37C
1.4e-05
-
Mycophenolic acid
-
potent, uncompetitive, reversible, inhibits both isozymes, prodrug is mycophenolate mofetil, isozyme IMPDH II IC50: 14 nM
1.5e-05
-
Mycophenolic acid
-
isozyme IMPDH II IC50: 15 nM
1.9e-05
-
Mycophenolic acid
P12268, P20839
pH 7.4, 37C
3.3e-05
-
Mycophenolic acid
P12268, P20839
pH 8.0, 25C
9.92e-05
-
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
0.000128
-
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
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
-
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
-
IC50: 0.045 mM, isozyme IMPDH II
1.8e-05
-
N-(2,3-dichlorophenyl)-2-[2-(1,3-thiazol-2-yl)-1H-benzimidazol-1-yl]acetamide
-
pH not specified in the publication, temperature not specified in the publication
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
-
IC50: 0.051 mM, isozyme IMPDH II
2.8e-05
-
N-(4-bromophenyl)-2-[2-(1,3-thiazol-2-yl)-1H-benzimidazol-1-yl]acetamide
-
pH not specified in the publication, temperature not specified in the publication
0.0017
-
N-(4-methoxyphenyl)-2-(3-methyl-4-oxo-3,4-dihydrophthalazin-1-yl)acetamide
-
pH 8.0, 25C
0.0023
-
N-(4-methoxyphenyl)-2-(3-methyl-4-oxo-3,4-dihydrophthalazin-1-yl)acetamide
-
mutant S250A/L444Y, pH 8.0, 25C
0.003
-
N-(4-methoxyphenyl)-2-(3-methyl-4-oxo-3,4-dihydrophthalazin-1-yl)acetamide
-
pH 8.0, 25C
0.049
-
N-(4-methoxyphenyl)-2-(3-methyl-4-oxo-3,4-dihydrophthalazin-1-yl)acetamide
-
pH 8.0, 25C
0.0006
-
N-(4-methoxyphenyl)-2-[2-(1,3-thiazol-4-yl)-1H-benzimidazol-1-yl]acetamide
-
pH 8.0, 25C
0.0006
-
N-(4-methoxyphenyl)-2-[2-(1,3-thiazol-4-yl)-1H-benzimidazol-1-yl]acetamide
-
mutant S250A/L444Y, pH 8.0, 25C
0.0006
-
N-(4-methoxyphenyl)-2-[2-(1,3-thiazol-4-yl)-1H-benzimidazol-1-yl]acetamide
-
pH 8.0, 25C
0.07
-
N-(4-methoxyphenyl)-2-[2-(1,3-thiazol-4-yl)-1H-benzimidazol-1-yl]acetamide
-
pH 8.0, 25C
5e-06
-
N-(5-phenyl-1,3-oxazol-2-yl)isoquinolin-6-amine
-
-
8e-06
-
N-(naphthalen-2-yl)-2-[2-(1,3-thiazol-2-yl)-1H-benzimidazol-1-yl]acetamide
-
pH not specified in the publication, temperature not specified in the publication
7e-06
-
N-(naphthalen-2-yl)-2-[2-(1,3-thiazol-4-yl)-1H-benzimidazol-1-yl]acetamide
-
pH not specified in the publication, temperature not specified in the publication
5.1e-05
-
N-(naphthalen-2-yl)-2-[2-(pyridin-2-yl)-1H-benzimidazol-1-yl]acetamide
-
pH 8.0, 22C
5.7e-05
-
N-(naphthalen-2-yl)-2-[2-(pyridin-2-yl)-1H-benzimidazol-1-yl]acetamide
-, Q81W29
pH 8.0, 22C
1.1e-06
-
N-(naphthalen-2-yl)-2-[2-(pyridin-2-yl)-5,6-dihydro-1H-benzimidazol-1-yl]acetamide
-
pH 8.0, 25C
1.9e-06
-
N-(naphthalen-2-yl)-2-[2-(pyridin-2-yl)-5,6-dihydro-1H-benzimidazol-1-yl]acetamide
-
mutant S250A/L444Y, pH 8.0, 25C
5.4e-06
-
N-(naphthalen-2-yl)-2-[2-(pyridin-2-yl)-5,6-dihydro-1H-benzimidazol-1-yl]acetamide
-
pH 8.0, 25C
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
-
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
-
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
-
isozyme IMPDH II IC50: 0.005 mM
4.5e-05
-
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
5.5e-05
-
N-tert-butyl-N'-[3-chloro-4-(1,3-oxazol-5-yl)phenyl]ethanediamide
-
isozyme IMPDH II IC50: 55 nM
1e-05
-
N-tert-butyl-N'-[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]ethanediamide
-
isozyme IMPDH II IC50: 10 nM
0.005
-
N-tert-butyl-N'-[4-(1,3-oxazol-5-yl)phenyl]ethanediamide
-
isozyme IMPDH II IC50: 0.005 mM
0.005
-
N-tert-butyl-N'-[4-(4-methyl-1,3-oxazol-5-yl)phenyl]ethanediamide
-
isozyme IMPDH II IC50: 0.005 mM
1.7e-05
-
N-[1-[6-(4-ethylpiperazin-1-yl)pyridin-3-yl]-1-methylethyl]-2-fluoro-9-oxo-9,10-dihydroacridine-3-carboxamide
-
-
4.7e-05
-
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
2.8e-05
-
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
2.1e-05
-
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
4.8e-05
-
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
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
-
isozyme IMPDH II IC50: 310 nM
2.1e-05
-
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
9.1e-05
-
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
1.2e-05
-
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
-
-
1.6e-05
-
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
1.8e-05
-
N-[2-(hydroxymethyl)cyclopentyl]-N'-[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]propanediamide
-
-
0.005
-
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
0.0016
-
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
0.005
-
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
5e-05
-
N-[3-bromo-4-(1,3-oxazol-5-yl)phenyl]-N'-tert-butylethanediamide
-
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
-
isozyme IMPDH II IC50: 0.005 mM
8.8e-05
-
N-[3-chloro-4-(1,3-oxazol-5-yl)phenyl]-5-phenyl-1,3-oxazol-2-amine
-
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
-
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
-
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
-
isozyme IMPDH II IC50: 190 nM
5.7e-05
-
N-[3-methoxy-4-(1,3-oxazol-4-yl)phenyl]-5-phenyl-1,3-oxazol-2-amine
-
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
-
isozyme IMPDH II IC50: 0.0016 mM
2e-05
-
N-[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]-5-phenyl-1,3-oxazol-2-amine
-
isozyme IMPDH II IC50: 20 nM
7.6e-05
-
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
0.00041
-
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
0.002
-
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
0.005
-
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
0.005
-
N-[3-methyl-4-(1,3-oxazol-4-yl)phenyl]-5-phenyl-1,3-oxazol-2-amine
-
isozyme IMPDH II IC50: 0.005 mM
0.005
-
N-[4-(1,3-oxazol-4-yl)phenyl]-5-phenyl-1,3-oxazol-2-amine
-
isozyme IMPDH II IC50: 0.005 mM
0.005
-
N-[4-(1,3-oxazol-5-yl)phenyl]-5-phenyl-1,3-oxazol-2-amine
-
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
-
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
-
isozyme IMPDH II IC50: 0.005 mM
0.001
-
pellynic acid
-
-
1.6e-05
-
phenyl N'-cyano-N-(3-[cyano[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]carbamimidamido]benzyl)imidocarbamate
-
-
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
-
IC50: 104 nM, isozyme IMPDH II
3.5e-05
-
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
-
-
1.3e-05
-
thiazofurin-5'-yl-2-ethyladenosin-5'-yl-difluromethylene bis(phosphonate)
P12268, P20839
pH 8.0, 25C
3e-05
-
thiazofurin-5'-yl-2-ethyladenosin-5'-yl-difluromethylene bis(phosphonate)
P12268, P20839
pH 8.0, 25C
1e-06
-
thiazole-4-carboxamide 2-ethyladenine dinucleotide
P12268, P20839
pH 8.0, 25C
1.4e-05
-
thiazole-4-carboxamide 2-ethyladenine dinucleotide
P12268, P20839
pH 8.0, 25C
0.00011
-
thiazole-4-carboxamide adenine dinucleotide
P12268, P20839
pH 8.0, 25C; pH 8.0, 25C
6e-06
-
VX-148
-
isozyme IMPDH II IC50: 6 nM
1.1e-05
-
VX-497
-
isozyme IMPDH II IC50: 11 nM
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
-
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
-
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
-
isozyme IMPDH II IC50: above 0.001 mM
9.6e-05
-
[(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
2e-05
-
[(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
8.6e-05
-
[(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
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.00055
-
-
in cell extracts
0.0015
-
-
strain NA6120
0.00649
-
-
-
0.0098
-
-
strain NA7821
0.015
-
-
strain NA6128 pBX121
0.236
-
-
-
0.57
-
-
-
1.1
1.5
-
; purified enzyme
1.18
-
-
-
1.3
-
-
-
5.03
-
-
-
18.75
-
-
; purified enzyme
additional information
-
-
-
additional information
-
-
-
additional information
-
-
-
additional information
-
-
-
additional information
-
-
activity in various organs
additional information
-
-
-
additional information
-
-
-
additional information
-
-
activity in crude extracts
additional information
-
-
-
additional information
-
-
activity is higher in erythrocytes than in mononuclear cells
additional information
-
Q4VRV6, Q4VRV8, -
-
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
additional information
-
-
activity in whole blood cells after application of prodrug mycophenolate mofetil
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7.4
-
-
assay at
7.5
7.6
-
assay at
7.7
-
-
at 37C
8
-
-
-
8
-
Q4VRV6, Q4VRV8, -
assay at; assay at
8
-
P20839
assay at
8
-
-
assay at
8
-
Q59Q46
assay at
8
-
-
assay at
8
-
-, I3WTS0
-
8.1
-
-
assay at
8.2
-
-, Q81W29
-
8.5
-
-
increase of activity with increasing pH up to 8.5
8.5
-
Q387Q3, -
-
9.5
-
-
40% of activity at pH 8.0
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6.7
9
-
pH 6.7: about 40% of activity maximum, pH 9.0: about 55% of activity maximum
7
9
-
pH 7: about 45% of activity maximum, pH 9: about 85% of activity maximum
7.5
8.7
-
pH 7.5: about 60% of activity maximum, pH 8.7: about 40% of activity maximum
7.5
9
-
pH 7.5: about 50% of activity maximum, pH 9: about 50% of activity maximum
7.5
9.5
-
pH 7.5: about 55% of activity maximum, pH 9.5: about 70% of activity maximum
8.5
10
-
pH 8.5: about 60% of activity maximum, pH 10: about 75% of activity maximum
additional information
-
-
pH-dependence of wild-type enzyme and mutant Y419F, overview
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
23
-
-
assay at
25
-
-
assay at
25
-
-
assay at
25
-
-
assay at
25
-
Q59Q46
assay at
25
-
-
assay at
30
-
-
assay at
35
-
-
assay at
37
-
-
assay at
37
-
Q4VRV6, Q4VRV8, -
assay at; assay at
37
-
P20839
assay at
37
-
-
assay at
37
-
-
assay at
39
-
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
hepatoma cell line
Manually annotated by BRENDA team
-
whole blood
Manually annotated by BRENDA team
-
; type II isoform predominates
Manually annotated by BRENDA team
-
HGPRT-deficient acute lymphoblastic leukemia cell line
Manually annotated by BRENDA team
-
CD14+-derived dendritic cells
Manually annotated by BRENDA team
-
leukemic cell line
Manually annotated by BRENDA team
-
HGPRT-deficient hybridoma cell line
Manually annotated by BRENDA team
-
; type I isoform is prevalent
Manually annotated by BRENDA team
-
peripheral blood lymphocytes
Manually annotated by BRENDA team
-
; type I isoform is prevalent
Manually annotated by BRENDA team
-
breast cancer cell line
Manually annotated by BRENDA team
-
leukemia cell
Manually annotated by BRENDA team
-
nitrogen-fixing
Manually annotated by BRENDA team
-
retinal-specific isoforms IMPDH1(546) and IMPDH1(595)
Manually annotated by BRENDA team
Q6P9U9
inosine monophosphate dehydrogenase is present in all immature cells throughout the retina during embryonic and neonatal development. Following eye opening and cell differentiation, its distribution is restricted to the photoreceptors and bipolar cell, becoming prominent in Muller cells with ageing. Type I enzyme does not play a role in early retinal development but type Igamma has greater activity after postnatal day 10. All forms of type I show an increased propensity to form intracellular macrostructures compared to type II
Manually annotated by BRENDA team
-
isoform IMPDH1 undergoes alternate splicing to produce at least two retinal isoforms. The abundance of isoforms differs between the species
Manually annotated by BRENDA team
-
; IMPDH1 predominates in the adult retina
Manually annotated by BRENDA team
-
nitrogen fixing nodules
Manually annotated by BRENDA team
-
highest activity of rat tissues tested
Manually annotated by BRENDA team
Q4VRV6, Q4VRV8, -
cultured in primary human foreskin fibroblasts; cultured in primary human foreskin fibroblasts
Manually annotated by BRENDA team
-
highest activity of rat tissues tested
Manually annotated by BRENDA team
additional information
-
type II isoform predominates in proliferating cells and is upregulated in neoplastic cells
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
most of the activity is associated with microsomal fraction
-
Manually annotated by BRENDA team
-
strong association of subunit Imd2 with actively transcribed genes, it is not recruited to nontranscribed regions. Serine 2 C-terminal domain phosphorylation of the elongating RNA polymerase II by Ctk1 kinase is required to recruit Imd2 to actively transcribed genes in vivo
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Borrelia burgdorferi (strain ATCC 35210 / B31 / CIP 102532 / DSM 4680)
Campylobacter jejuni subsp. jejuni serotype O:2 (strain NCTC 11168)
Cryptosporidium parvum (strain Iowa II)
Legionella pneumophila subsp. pneumophila (strain Philadelphia 1 / ATCC 33152 / DSM 7513)
Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961)
Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961)
Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961)
Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961)
Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961)
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
43640
-
-
calculated from amino acid composition
44000
-
-
SDS-PAGE
50000
-
-
SDS-PAGE
50000
-
-
SDS-PAGE
52200
-
-
(His)6 IMPDH protein, Western blot analysis
52330
-
-
MALDI-MS
52700
-
-
SDS-PAGE
53770
-
-
calculated from amino acid composition
54000
-
-
SDS-PAGE
55260
-
-
type I, calculated from amino acid sequence
55390
-
-
calculated from amino acid sequence
55560
-
-
calculated from amino acid sequence
55680
-
-
type II, calculated from amino acid sequence
56000
-
-
SDS-PAGE, two different proteins of identical molecular weight but differently charged
56000
-
-
-
56000
-
-
SDS-PAGE
56000
-
-
SDS-PAGE
56000
-
-
SDS-PAGE
56280
-
-
calculated from amino acid sequence
57000
-
-
SDS-PAGE
58000
-
-
SDS-PAGE
58000
-
-
SDS-PAGE
60000
-
-
SDS-PAGE
86000
-
-
smallest active species has a molecular weight of 86000, after polymerization in the absence of reducing agents the largest species has a molecular weight of 248000, gel filtration
90000
100000
-
basic catalytic molecular species, the species of this MW are of more than one type, under following conditions 2 species of indicated MW are present in approximately equal amount: 56000 and 95000 in 0.02 M phosphate at pH 7.4, 185000 and 300000 in 0.1 M Tris-citrate at pH 8.1, 185000 and 300000 in 0.02 M Tris-citrate at pH 7.4 or 8.1 containing 0.1 M KCl, 0.1 M NaCl or 0.25 M KCl, 90000 and 180000 in 0.38 M Tris-HCl, ultracentrifugation, sucrose density gradient sedimentation
127000
-
-
Yoshida sarcoma ascites tumor cells, gel filtration in presence of 10% (NH4)2SO4
165000
-
-
sedimentation equilibrium
200000
-
-
sedimentation coefficient
200000
-
-
gel filtration
204000
-
-
gel filtration
225000
-
-
gel filtration
232000
-
-
gel filtration
245000
-
-
rat hepatoma 3924 A cells, gel filtration
249000
-
-
gel filtration, smallest enzymatically active species
389000
-
Q387Q3, -
sedimentation velocity analysis
420000
-
Q387Q3, -
gel fitlration
additional information
-
-
nucleotide sequence of IMP dehydrogenase gene
additional information
-
-
enzyme tends to aggregate owing to its own physicochemical characteristics
additional information
-
-
various molecular species
additional information
-
-
equilibrium sedimentation results suggest monomeric, dimeric and tetrameric forms and higher order aggregates
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 62000 + x * 40000, gel filtration in presence of guanidine
?
-
multiples with a basic unit of 160000
?
-
? * 58000, identical subunits
?
-
x * 54000, SDS-PAGE
?
-
MAD analysis
?
-
x * 56000, canonical isoforms of IMPDH1 and smaller retinal isoform, x * 65000, large retinal isoform, calculated
?
E3P6S3
x * 58000, SDS-PAGE
?
-
x * 58000, SDS-PAGE
?
P42851, -
x * 52900, calculated from sequence
?
-, I3WTS0
x * 57000, SDs-PAGE, His-tagged protein
?
Cryptococcus neoformans H99
-
x * 58000, SDS-PAGE
-
dimer
-
2 * 38000, amino acid analysis
dimer
-
2 * 68000, Yoshida sarcoma ascites tumor cells, SDS-PAGE
tetramer
-
4 * 60000, rat hepatoma 3924 A cells, SDS-PAGE
tetramer
-
4 * 50000, SDS-PAGE
tetramer
-
4 * 58000, SDS-PAGE
tetramer
-
-
tetramer
-
4 * 56000 density gradient centrifugation
tetramer
-
4 * 56000 gel filtration
tetramer
-
-
tetramer
-
the enzyme contains a cystathione beta-synthase-like subdomain which is involved in nucleic acid binding
tetramer
-
the enzyme forms a homotetramer with four active sites and an open dehydrogenase conformation
tetramer
-
the enzyme forms a homotetramer with four active sites
tetramer
-
4 * 55000, SDS-PAGE
tetramer
-
crystallography
tetramer
-
4 * 56000; 4 * 56000
heptamer
Q387Q3, -
7 * 57000, SDS-PAGE
additional information
-
the C-terminal extension unique to the retinal isoforms of IMPDH blocks the nucleic acid binding site
additional information
-
IMPDH associates tightly with glycosomal protein sorting receptor PEX5
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
in a phosphate ion-bound form and in complex with its substrate, inosine 5'-monophosphate, and product, xanthosine 5'-monophosphate, to 2.38-2.65 A resolution. The enzyme monomer has a typical two-domain structure, the catalytic domain, which is a TIM barrel, and the CBS domain. In all structures, each monomer contains a ligand bound in the active site, i.e.phosphate anion in the apo structure and IMP and XMP in the substrate and product-bound structures, respectively. In all the structures, the CBS domains are partially disordered
-, Q81W29
at 2.4 A resolution
-
in complex with sulfate, at 2.4 A resolution
-
in complex with inosine 5'-phosphate and mycophenolic acid at 2.6 A resolution
-
in complex with xanthosine 5'-phosphate, inhibitor mycophenolic acid and K+, at 2.6 A resolution
-
in complex with NAD+ and IMP, to 2.5 A resolution. Space group I422
E3P6S3
in complex with NAD+ and IMP, to 2.5 A resolution. Space group I422
-
hanging drop vapour diffusion method, to 3.2 A resolution, space group P21212. In complex with inhibitor N-(4-bromophenyl)-2-[2-(1,3-thiazol-2-yl)-1H-benzimidazol-1-yl]acetamide, to 2.8 A resolution. The thiazole ring of the inhibitor stacks against the purine ring of IMP perpendicularly, and the remainder of the inhibtor extends across the subunit interface into a pocket in the adjacent monomer, where the bromoaniline moiety interacts with Tyr358 from the adjacent subunit. This residue forms a hydrogen-bonding network involving Glu329, Ser354, Thr221, and possibly the amide nitrogen of N-(4-bromophenyl)-2-[2-(1,3-thiazol-2-yl)-1H-benzimidazol-1-yl]acetamide. Residues Ser22, Pro26, Gly357 of the adjacent subunit and Ala165 form the remainder of the inhibitor binding pocket. With the exception of Thr221, all of these residues are different in human IMPDHs
-
enzyme type II complexed with 6-Cl-IMP and selenazole-4-carboxamide adenine dinucleotide, no method mentioned
P12268
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; 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
P12268, P20839
molecular modeling of type II enzyme in complex with inhibitor 1_1_1.205_2.3
-
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; type I isoform, in complex with 6-chloropurine riboside 5'-monophosphate at 2.5 A resolution
-
modeling of enzyme in complex with eicosadienoic acid. Eicosadienoic acid binds to residue C331 in the active site
-
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
-
to 2.25 A resolution. Strucuture is a homotetramer of subunits dominated by a (beta/alpha)8-barrel fold. The cystathionine beta-synthase domains, residues 92-204, are not present in the model owing to disorder. A loop that creates part of the active site is composed of residues 297-315, links alpha8 and beta9 and carries the catalytic Cys304
-, Q9HXM5
in complex with xanthosine 5'-phosphate at 2.1 A resolution
-
in complex with inosine 5'-phosphate at 1.9 A resolution
-
in complex with inosine 5'-phosphate, at 1.9 A resolution
-
tetramer structure of IMPDH shows square planar geometry
-
vapor diffusion method using hanging drops
-
at 2.18 A resolution
-
analysis of crystal structures. The Cys319 loop has different conformations during the dehydrogenase and hydrolase reactions as suggested by the crystal structures. The structure of the Cys319 loop modulates the closure of themobile flap. This conformational change converts the enzyme from a dehydrogenase into hydrolase, suggesting that the conformation of the Cys319 loop may gate the catalytic cycle
-
at 2.3 A resolution, in complex with inosine 5'-phosphate and beta-methylene-thiazole-4-carboxyamide-adenine dinucleotide at 2.2 A resolution, in complex with xanthosine 5'-phosphate and NAD+ at 2.15 A resolution, in complex with xanthosine 5'-phosphate and mycophenolic acid at 2.2 A resolution, in complex with RVP and mycophenolic acid at 2.15 A resolution, in complex with 4-carbamoyl-1-beta-D-ribofuranosylimidazolium-5-olate-5'-phosphate at 2.0 A resolution
-
no method mentioned
-
purified recombinant full-length enzyme and alphabeta core domain in complex with inosine 5'-phosphate and beta-methylene-thiazole-4-carboxamide adenine dinucleotide, X-ray diffraction structure determination and analysis at 2.2 A resolution, molecular replacement
-
wild-type at 2.3 A resolution, in complex with xanthosine 5'-phosphate, at 2.6 A resolution, in complex with inhibitor ribavirin-monophosphate, at 1.9 A resolution, in complex with inhibitors ribavirin-monophosphate and mycophenolic acid, at 2.5 A resolution, in complex with inosine 5'-phosphate, at 2.2 A resolution, in complex with inosine 5'-phosphate and inhibitor mycophenolic acid, at 1.95 A resolution, in complex with xanthosine 5'-phosphate and inhibitor mycophenolic acid, at 2.2 A resolution, in complex with xanthosine 5'-phosphate and NAD+, at 2.15 A resolution. Mutant DELTA(101-226) in complex with inosine 5'-phosphate and inhibitor beta-CH2-tiazofurin adenine dinucletoide, at 2.2 A resolution or in complex with inhibitor mizoribine monophosphate, at 2 A resolution
-
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
2
-
-
60% loss of activity within 4 days
4
-
-
13% loss of activity within 1 day
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
0.001 mM p-chloromercuribenzoate stabilizes
-
50% loss of activity when freeze-dried
-
activity is maintained when stored for 3 weeks at -20C, during which it can be thawed and frozen twice and kept at 2C for two 24-h periods
-
bovine serum albumin stabilizes during dialysis
-
purified enzyme very unstable
-
glycerol stabilizes
-
half life is less than 3 hours, NAD+ and IMP stabilize
-
ORGANIC SOLVENT
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
dimethyl sulfoxide
-, Q81W29
up to 15-20% increase IMP dehydrogenase activity
dimethyl sulfoxide
-
up to 15-20% increase IMP dehydrogenase activity
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
0C, p-chloromercuribenzoate, several weeks without loss of activity
-
frozen, 2 weeks, no loss of activity
-
-80C, most activity is lost
-
-17C no loss of activity for several months
-
2C, 50% loss of activity after 2-3 days in dilutions with water
-
-17C, 24 h, 10% loss of activity
-
4C, 24 h, 13% loss of activity
-
frozen in 5 mM mercaptoethanol, 3 months, 50% loss of activity
-
-80C, can be indefinitely stored without loss of activity
-
4C, no loss of activity after 3 days
-
-80C, purified protein remains active for more than 18 months
-
-15C, 10% loss of activity within 2 weeks and 40% loss after 6 weeks
-
-70C, 10 mg/ml bovine serum albumin, 3 weeks, 15% loss of activity
-
-20C , no appreciable loss of activity for a few weeks in 20-25% glycerol
-
-20, no significant loss of activity for serveral weeks after ammonium sulfate precipitation, no loss of activity after Sephacryl S400 chromatography
-
4C, NAD+, IMP, 20% loss of activity after 18 h
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
partial purification
-
95% homogeneity
-
recombinant enzyme from wild-type and mutant enzyme-deficient Escherichia coli strain H712
Q59Q46
partially 20fold by ammonium sulfate fractionation; partial purification
-
recombinant protein
E3P6S3
recombinant protein
-
recombnant enzyme
-
to more than 95% purity
-
affinity chromatography; homogeneity; native enzyme about 20fold to homogeneity by ammonium sulfate fractionation, gel filtration, and affinity chromatography
-
affinity chromatography; large scale
-
affinity chromatography; native enzyme about 14fold by affinity chromatography on different immobilized dyes, elution by salt gradient, over 90% purity of the enzyme, method development and optimization, overview
-
derepressed mutant
-
partial purification
-
homogeneity
-
MOLT 4F human T-lymphoblasts
-
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
-
recombinant wild-type and mutant IMPDH1s from Escherichia coli strain H712 by two steps of affinity chromatography, and gel filtration, to over 95% purity
P20839
P-388 lymphocytic leucemia tumor cells
-
partial purification
-
hepatoma cells 3924 A
-
hepatoma cells 3924 A; homogeneitiy
-
homogeneitiy
-
native enzyme from hepatoma 3924A cells to homogeneity
-
partially by ammonium sulfate fractionation; partial purification
-
partial purification
-
by Ni-NTA affinity chromatography
-
homogeneity
-
recombinant FLAG-tagged large splicing variant by immunoaffinity
Q4VRV6, Q4VRV8, -
homogeneity
-
recombinant full-length enzyme and alphabeta core domain of the enzyme from Escherichia coli
-
; native enzyme over 140fold from nitrogen-fixing nodules by ammonium sulfate fractionation, gel filtration, and affinity chromatography to homogeneity
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expression in Escherichia coli
-, I3WTS0
Bacillus subtilis
-
gene IMH3, DNA sequence determination of wild-type and mutant IMH3, expression in enzyme-deficient Escherichia coli strain H712, subcloning in Escherichia coli strain DH5alpha
Q59Q46
Chinese hamster; human
-
expression in Escherichia coli
E3P6S3
expression in Escherichia coli
-
expressed in Escherichia coli
-
expression in Escherichia coli
-
Chinese hamster; human
-
expressed in Escherichia coli; expressed in Escherichia coli
-
expressed in Morris hepatoma 3924A cells
-
expression as fusion protein with green fluorescence protein, in HEK-293 cell, HeLa cell and COS cell, and expression in Escherichia coli
-
expression in Eshcerichia coli; expression in Eshcerichia coli
P12268, P20839
expression in HeLa cell and CHO cell; expression in HeLa cell and CHO cell
P12268, P20839
expression of full-length type I isozyme and of the His-tagged type I isozyme subdomain in Escherichia coli
-
expression of His-tagged type II IMPDH in Escherichia coli strain BL21(DE3)
-
expression of isoyzmes IMPDH I and IMPDH II in Escherichia coli strain BL21(DE3)
-
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
P20839
isoform IMPDH2, expression in Escherichia coli
-
overexpression of IMPDH2 in human erythroleukemia K562 cells, expression analysis, the enzyme expression affects the cytotoxicity of methotrexate, overview
-
type I and type II
-
type II
-
expression in Escherichia coli
-
genes from: Leishmania donovani
-
isoform IMPDH2, expression in Escherichia coli
P24547
expression in Escherichia coli
-
pET32 expression plasmid, from which the impdh gene is inducibly overexpressed in Escherichia coli BL21 (DE3) to produce IMPDH with a hexahistidyl N-terminus
-
DNA and amino acid sequence determination and analysis, two splicing variants, a short and a large one, overview; DNA and amino acid sequence determination and analysis, two splicing variants, a short and a large one, overview, expression of FLAG-tagged large splicing variant in the parasite with localization in the cytoplasm
Q4VRV6, Q4VRV8, -
expressed in Escherichia coli
P50097
expression of the full-length enzyme and the alphabeta core domain of the enzyme in Escherichia coli
-
expression of wild-type and mutant enzyme core domains in Escherichia coli
-
expression of wild-type and mutant enzymes in enzyme-deficient Escherichia coli strain H712
-
expression in Escherichia coli
Q387Q3, -
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
enhanced expression of the type 2 isozyme in leukemias and other proliferating human cells
-
increase in IMPDH activity in erythrocytes after kidney transplantation
-
IMPDH protein expression is transiently increased during differentiation of 3T3-L1 preadipocytes. Total IMPDH protein levels and activity are highest around day 3
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
A251T
Q59Q46
the mutation affects the enzyme structure so that the mutant shows altered sensitivity to inhibitors compared to the wild-type enzyme
A251T
-
is 4fold less sensitive to mycophenolic acid but 40fold more sensitve to mizoribine monophosphate. Mutation does not affect kcat but decreases Km values for both substrates, is catalytically more efficient. Mutation renders the enzyme resistant to NAD+ substrate inhibition, stabilizes the closed conformation, which has opposing effects on enzyme susceptiblities to mycophenolic acid and mizoribine monophosphate
C305A
-
the guaBDELTACBS phenotype can be complemented in trans by a mutant guaB allele, which encodes the catalytically disabled IMPDHC305A protein containing an intact Bateman domain
D13A
-
is activated by Mg2+ and Ca2+ in lieu of K+
D248A
-
selectively impairs NAD binding
D338A
-
affects Kcat more than 600fold and increases the Km for inosine 5'-phosphate, hydride transfer rate is diminished at least 5000fold, rate of inactivation by 6-chloroinosine 5'-phosphate is increased 3fold
D50A
-
is inhibted by Mg2+ and Ca2+, Mg2+ inhibition becomes uncompetitive with respect to K+ and competitive with both inosine 5'-phosphate and NAD+, in contrast to the wild-type enzyme, the mutant is inactive in the absence of K+
S250A/L444Y
-
mutation of residues corresponding to structural motif A250/Y358 of Cryptosporidium parvum. Mutation renders the enzyme susceptible to inhibitors
A285T
P20839
site-directed mutagenesis of IMPDH1, similar activity and protein stability compared to the wild-type enzyme
A462T
-
increase in the Ki for mycophenolic acid
C331A
-
mutated type 2 isozyme in the inosine 5'-phosphate binding site, which results in less than 0.1% activity
D226N
P20839
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
-
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
-
IMPDH1 polymorphism, which is associated with retinal degeneration
D301N
-
IMPDH1 polymorphism, which does not affect protein function
D364A
-
mutated type 2 isozyme in the inosine 5'-phosphate binding site, which results in less than 0.1% activity
F465S/N470G
-
increase in the Ki for mycophenolic acid
G324D
-
IMPDH1 polymorphism, which does not affect protein function
G326A
-
mutated type 2 isozyme in the inosine 5'-phosphate binding site, which results in less than 0.1% activity
G519R
-
IMPDH1 polymorphism, which does not affect protein function
H296R
-
IMPDH1 polymorphism, which does not affect protein function
H372P
-
IMPDH1 polymorphism, which is associated with retinal degeneration
K409A
-
mutated type 2 isozyme, low-activity protein with increased Km value
L263F
-
site-directed mutagenesis, about 10% of wild-type activity
L263F
-
IMPDH2 polymorphism, which decreases the value of kcat by a factor of 10
N198K
-
IMPDH1 polymorphism, which is associated with retinal degeneration and with Leber congenital amaurosis
Q277R
-
increase in the Ki for mycophenolic acid
Q277R/A462T
-
increase in the Ki for mycophenolic acid
Q441E
-
less than 0.045% of wild type activity, therefore no further characterization possible
R105W
-
IMPDH1 polymorphism, which is associated with retinal degeneration and with Leber congenital amaurosis
R224P
P20839
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
R231P
-
IMPDH1 polymorphism, which causes autosomal dominant retinitis pigmentosa
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
T116M
-
IMPDH1 polymorphism, which is associated with retinal degeneration
V268I
P20839
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
Y111A
-
mutated type 2 isozyme, low-activity protein with increased Km value
E421Q
-
full enzymatic activity
R406A
-
no enzymatic activity
Y450A
-
25% of enzymatic activity
C319S
-
is essentially inactive, two-step binding process for inosine 5'-phosphate remains
DELTA(101-226)
-
crystallized in complex with inosine 5'-phosphate and inhibitor beta-CH2-tiazofurin adenine dinucletoide, at 2.2 A resolution or in complex with inhibitor mizoribine monophosphate, at 2 A resolution
E323A
-
substitution increases the equilibrium constant for the dehydrogenase step but decreases the equilibrium between open and closed conformations of a mobile fl