Any feedback?
Information on EC 1.3.5.2 - dihydroorotate dehydrogenase (quinone) and Organism(s) Homo sapiens and UniProt Accession Q02127
for references in articles please use BRENDA:EC1.3.5.2Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
1.3.5.2 dihydroorotate dehydrogenase (quinone)IUBMB Comments
This Class 2 dihydroorotate dehydrogenase enzyme contains FMN . The enzyme is found in eukaryotes in the mitochondrial membrane, in cyanobacteria, and in some Gram-negative and Gram-positive bacteria associated with the cytoplasmic membrane [2,5,6]. The reaction is the only redox reaction in the de-novo biosynthesis of pyrimidine nucleotides [2,4]. The best quinone electron acceptors for the enzyme from bovine liver are ubiquinone-6 and ubiquinone-7, although simple quinones, such as benzoquinone, can also act as acceptor at lower rates . Methyl-, ethyl-, tert-butyl and benzyl (S)-dihydroorotates are also substrates, but methyl esters of (S)-1-methyl and (S)-3-methyl and (S)-1,3-dimethyldihydroorotates are not . Class 1 dihydroorotate dehydrogenases use either fumarate (EC 1.3.98.1), NAD+ (EC 1.3.1.14) or NADP+ (EC 1.3.1.15) as electron acceptor.
Specify your search results
Word Map
- 1.3.5.2
- pyrimidine
- falciparum
- plasmodium
- leflunomide
- brequinar
- uridine
- malaria
- arthritis
-
antimalarial
-
rheumatoid
- dihydroorotase
-
salvage
- teriflunomide
-
dhods
- autoimmune
- orotidine
- ump
- atovaquone
- triazolopyrimidine
-
flavoenzyme
- medicine
-
phosphoribosyltransferase
-
antirheumatic
- coq
- drug development
- decylubiquinone
-
dmards
- synthesis
-
species-selective
-
pyre
- pharmacology
-
isoxazole
-
transcarbamoylase
- 5-fluoroorotate
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
dihydroorotate dehydrogenase, pfdhodh, hdhodh, dho-dh, hsdhodh, dihydroorotate dehydrogenase (quinone), 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
DHODH
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
(S)-dihydroorotate + a quinone = orotate + a quinol
fourth step in biosynthesis of pyrimidines. Two domains: alpha/beta-barrel domain containing the active site, one alpha-helical domain that forms the opening of a tunnel leading to active site
-
(S)-dihydroorotate + a quinone = orotate + a quinol
in liver, myocardium and skeletal muscle tissues the activity intensities vary from animal to animal, but are similar in ileum, colon and kidney cortex. Cardiac enzyme expresses a pronounced oxidase activity
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
redox reaction
-
-
-
-
oxidation
-
-
-
-
reduction
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
(S)-dihydroorotate:quinone oxidoreductase
This Class 2 dihydroorotate dehydrogenase enzyme contains FMN [4]. The enzyme is found in eukaryotes in the mitochondrial membrane, in cyanobacteria, and in some Gram-negative and Gram-positive bacteria associated with the cytoplasmic membrane [2,5,6]. The reaction is the only redox reaction in the de-novo biosynthesis of pyrimidine nucleotides [2,4]. The best quinone electron acceptors for the enzyme from bovine liver are ubiquinone-6 and ubiquinone-7, although simple quinones, such as benzoquinone, can also act as acceptor at lower rates [2]. Methyl-, ethyl-, tert-butyl and benzyl (S)-dihydroorotates are also substrates, but methyl esters of (S)-1-methyl and (S)-3-methyl and (S)-1,3-dimethyldihydroorotates are not [2]. Class 1 dihydroorotate dehydrogenases use either fumarate (EC 1.3.98.1), NAD+ (EC 1.3.1.14) or NADP+ (EC 1.3.1.15) as electron acceptor.
CAS REGISTRY NUMBER
COMMENTARY
59088-23-2
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(S)-dihydroorotate + 2,6-dichlorophenolindophenol
orotate + reduced 2,6-dichlorophenolindophenol
-
-
-
?
(S)-dihydroorotate + decylubiquinone
orotate + reduced decylubiquinone
-
-
-
?
dihydroorotate + 2,6-dichlorophenolindophenol
orotate + reduced 2,6-dichlorophenolindophenol
-
-
-
?
(S)-dihydroorotate + 2,3-dimethoxy-5-methyl-6-(3-methyl-2-butenyl)-1,4-benzoquinone
orotate + reduced 2,3-dimethoxy-5-methyl-6-(3-methyl-2-butenyl)-1,4-benzoquinone
Q02172
-
-
-
?
(S)-dihydroorotate + 2,6-dichlorophenolindophenol
orotate + reduced 2,6-dichlorophenolindophenol
(S)-dihydroorotate + acceptor
orotate + reduced acceptor
-
ubiquinone-6 tested as electron acceptor
-
?
(S)-dihydroorotate + decylubiquinone
orotate + reduced decylubiquinone
Q02172
-
-
-
?
L-dihydroorotate + decylubiquinone
orotate + reduced decylubiquinone
-
-
-
-
?
dihydroorotate + coenzyme Q0
orotate + reduced coenzyme Q0
-
-
-
?
(S)-dihydroorotate + 2,6-dichlorophenolindophenol
orotate + reduced 2,6-dichlorophenolindophenol
Q02172
-
-
-
?
(S)-dihydroorotate + 2,6-dichlorophenolindophenol
orotate + reduced 2,6-dichlorophenolindophenol
-
-
-
-
?
(S)-dihydroorotate + ubiquinone
orotate + ubiquinol
-
decylubiquinone as electron acceptor
-
?
(S)-dihydroorotate + ubiquinone
orotate + ubiquinol
-
fourth enzyme in pyrimidine synthesis
-
?
(S)-dihydroorotate + ubiquinone
orotate + ubiquinol
-
fourth enzyme in pyrimidine synthesis
-
ir
(S)-dihydroorotate + ubiquinone
orotate + ubiquinol
-
six-step biosynthesis of pyrimidine uridine monophosphate
-
?
(S)-dihydroorotate + ubiquinone
orotate + ubiquinol
-
fourth step in synthesis of uridine 5'-monophosphate
-
?
dihydroorotate + acceptor
orotate + reduced acceptor
-
-
-
-
?
dihydroorotate + acceptor
orotate + reduced acceptor
-
acceptor (low activity): 1,4-naphthoquinone, 5,8-hydroxy-naphthoquinone, juglon, plumbagin, polyporic acid
-
-
?
dihydroorotate + acceptor
orotate + reduced acceptor
-
acceptor: ubiquinone
-
-
?
L-dihydroorotate + FMN
orotate + FMNH2
-
DHODH catalyzes the FMN-dependent oxidation of dihydroorotate to produce orotic acid. Two separate half reactions are required to complete the catalytic cycle: 1. oxidation of dihydroorotate driven by the reduction of FMN and, 2. reoxidation of FMNH2 to regenerate the active enzyme
-
-
?
additional information
?
-
computational method to investigate potential proton relay pathways in the active site of the enzyme
-
-
?
additional information
?
-
-
computational method to investigate potential proton relay pathways in the active site of the enzyme
-
-
?
additional information
?
-
reduction of decylubiquinone (DUQ) is stoichiometrically equivalent to reduction of 2,6-ichloroindophenol (DCIP) resulting in the decrease in absorbance at 610 nm, which is measured
-
-
-
additional information
?
-
-
reduction of decylubiquinone (DUQ) is stoichiometrically equivalent to reduction of 2,6-ichloroindophenol (DCIP) resulting in the decrease in absorbance at 610 nm, which is measured
-
-
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(S)-dihydroorotate + ubiquinone
orotate + ubiquinol
-
fourth enzyme in pyrimidine synthesis
-
?
(S)-dihydroorotate + ubiquinone
orotate + ubiquinol
-
fourth enzyme in pyrimidine synthesis
-
ir
(S)-dihydroorotate + ubiquinone
orotate + ubiquinol
-
six-step biosynthesis of pyrimidine uridine monophosphate
-
?
(S)-dihydroorotate + ubiquinone
orotate + ubiquinol
-
fourth step in synthesis of uridine 5'-monophosphate
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
FMN
Lys100 and Lys225 enhance the structural stability of the active site by hydrogen bonding to the FMN cofactor
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(2Z)-2-cyano-3-cyclopropyl-3-hydroxy-N-[4-(trifluoromethyl)phenyl]prop-2-enamide
inhibitor based on the active metabolite of the anti-inflammatory drug leflunomide. Comparison of inhibitory effect and binding to human and Plasmodium falciparum enzyme
-
(2Z)-2-cyano-N-(2',3-dichlorobiphenyl-4-yl)-3-hydroxybut-2-enamide
inhibitor based on the active metabolite of the anti-inflammatory drug leflunomide. Comparison of inhibitory effect and binding to human and Plasmodium falciparum enzyme
-
(2Z)-2-cyano-N-(2,2'-dichlorobiphenyl-4-yl)-3-hydroxybut-2-enamide
inhibitor based on the active metabolite of the anti-inflammatory drug leflunomide. Comparison of inhibitory effect and binding to human and Plasmodium falciparum enzyme
-
(2Z)-2-cyano-N-(2,3'-dichlorobiphenyl-4-yl)-3-hydroxybut-2-enamide
inhibitor based on the active metabolite of the anti-inflammatory drug leflunomide. Comparison of inhibitory effect and binding to human and Plasmodium falciparum enzyme
-
(2Z)-2-cyano-N-(3'-ethoxybiphenyl-4-yl)-3-hydroxybut-2-enamide
inhibitor based on the active metabolite of the anti-inflammatory drug leflunomide. Comparison of inhibitory effect and binding to human and Plasmodium falciparum enzyme
-
(2Z)-N-(2'-chlorobiphenyl-4-yl)-2-cyano-3-hydroxybut-2-enamide
inhibitor based on the active metabolite of the anti-inflammatory drug leflunomide. Comparison of inhibitory effect and binding to human and Plasmodium falciparum enzyme
-
(2Z)-N-(3-chloro-2'-methoxybiphenyl-4-yl)-2-cyano-3-hydroxybut-2-enamide
inhibitor based on the active metabolite of the anti-inflammatory drug leflunomide. Comparison of inhibitory effect and binding to human and Plasmodium falciparum enzyme
-
(2Z)-N-(biphenyl-4-yl)-2-cyano-3-hydroxybut-2-enamide
inhibitor based on the active metabolite of the anti-inflammatory drug leflunomide. Comparison of inhibitory effect and binding to human and Plasmodium falciparum enzyme
(2Z)-N-[2'-chloro-3-(trifluoromethyl)biphenyl-4-yl]-2-cyano-3-hydroxybut-2-enamide
inhibitor based on the active metabolite of the anti-inflammatory drug leflunomide. Comparison of inhibitory effect and binding to human and Plasmodium falciparum enzyme
-
1,4-benzoquinone
3.9fold selectivity for Schistosoma mansoni over human enzyme
2-(1,1-difluoroethyl)-5-methyl-N-[4-(pentafluoro-lambda6-sulfanyl)phenyl][1,2,4]triazolo[1,5-a]pyrimidin-7-amine
i.e. DSM265
-
2-(2'-fluoro-[1,1'-biphenyl]-4-yl)-3-methyl-6-(trifluoromethyl)-1,7-naphthyridine-4-carboxylic acid
-
-
2-(2,3-dichloroanilino)-3-hydroxynaphthalene-1,4-dione
6.5fold selectivity for Schistosoma mansoni over human enzyme
-
2-(2-chloroanilino)-3-hydroxynaphthalene-1,4-dione
10.4fold selectivity for Schistosoma mansoni over human enzyme
-
2-(3-chloroanilino)-3-hydroxynaphthalene-1,4-dione
7fold selectivity for Schistosoma mansoni over human enzyme
-
2-(4-(2-(trifluoromethyl)pyridin-3-yl)phenyl)quinoline-4-carboxylic acid
-
-
2-(4-(2-chloro-6-methylpyridin-3-yl)phenyl)-3-methyl-1,7-naphthyridine-4-carboxylic acid
-
-
2-(4-(2-chloro-6-methylpyridin-3-yl)phenyl)-3-methylquinoline-4-carboxylic acid
-
-
2-(4-(2-chloro-6-methylpyridin-3-yl)phenyl)-6-fluoro-3-methylquinoline-4-carboxylic acid
-
-
2-(4-(2-chloro-6-methylpyridin-3-yl)phenyl)quinoline-4-carboxylic acid
-
-
2-(4-(2-chloropyridin-3-yl)phenyl)-3,6-dimethylquinoline-4-carboxylic acid
-
-
2-(4-(2-chloropyridin-3-yl)phenyl)-3-methyl-1,7-naphthyridine-4-carboxylic acid
-
-
2-(4-(2-chloropyridin-3-yl)phenyl)-3-methyl-6-(trifluoromethyl)-1,7-naphthyridine-4-carboxylic acid
-
-
2-(4-(2-chloropyridin-3-yl)phenyl)-3-methylquinoline-4-carboxylic acid
-
-
2-(4-(2-chloropyridin-3-yl)phenyl)-6-fluoro-3-methylquinoline-4-carboxylic acid
the compound possesses significant oral bioavailability (F = 56%) and an elimination t1/2 = 2.78 h, pharmacokinetic parameters, overview
-
2-(4-(2-fluoro-6-methylpyridin-3-yl)phenyl)-3-methylquinoline-4-carboxylic acid
-
-
2-(4-(2-fluoropyridin-3-yl)phenyl)-3-methylquinoline-4-carboxylic acid
-
-
2-(4-(4-(trifluoromethyl)pyridin-3-yl)phenyl)quinoline-4-carboxylic acid
-
-
2-(4-chloroanilino)-3-hydroxynaphthalene-1,4-dione
2.9fold selectivity for Schistosoma mansoni over human enzyme
-
2-(4-fluoroanilino)-3-hydroxynaphthalene-1,4-dione
3fold selectivity for human over Schistosoma mansoni enzyme
-
2-([1,1'-biphenyl]-4-yl)-3-methyl-1,6-naphthyridine-4-carboxylic acid
-
-
2-([1,1'-biphenyl]-4-yl)-3-methyl-1,7-naphthyridine-4-carboxylic acid
-
-
2-([1,1'-biphenyl]-4-yl)-3-methyl-1,8-naphthyridine-4-carboxylic acid
-
-
2-([1,1'-biphenyl]-4-yl)-3-methyl-6-(trifluoromethyl)-1,7-naphthyridine-4-carboxylic acid
-
-
2-hydroxy-3-(3-methylbutyl)naphthalene-1,4-dione
30.8fold selectivity for Schistosoma mansoni over human enzyme
-
2-hydroxy-3-(4-phenylpiperazin-1-yl)naphthalene-1,4-dione
9.6fold selectivity for Schistosoma mansoni over human enzyme
-
2-[(2,3-dihydro-1,4-benzodioxin-6-yl)amino]-3-hydroxynaphthalene-1,4-dione
2fold selectivity for human over Schistosoma mansoni enzyme
-
2-[(2,5-dichlorophenyl)sulfanyl]-5-ethyl[1,2,4]triazolo[1,5-a]pyrimidin-7-ol
compound has therapeutically relevant activity against human enzyme
2-[(2,5-dichlorophenyl)sulfanyl]-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-ol
compound has therapeutically relevant activity against human enzyme
2-[(3,4-dichlorophenyl)sulfanyl]-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-ol
compound is less active with human enzyme but good inhibitor of Plasmodium falciparum enzyme
2-[(4-chlorophenyl)sulfanyl]-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-ol
compound is less active with human enzyme but good inhibitor of Plasmodium falciparum enzyme
2-[4-(2,3-dichlorophenyl)piperazin-1-yl]-3-hydroxynaphthalene-1,4-dione
4.1fold selectivity for Schistosoma mansoni over human enzyme
-
2-[4-(4-chlorophenyl)piperazin-1-yl]-3-hydroxynaphthalene-1,4-dione
20.3fold selectivity for Schistosoma mansoni over human enzyme
-
3-(3-methylbut-2-en-1-yl)-1,4-dioxo-1,4-dihydronaphthalen-2-yl 4-methylbenzene-1-sulfonate
4.0fold selectivity for human over Schistosoma mansoni enzyme
-
6-chloro-2-(4-(2-chloro-6-methylpyridin-3-yl)phenyl)-3-methylquinoline-4-carboxylic acid
-
-
6-chloro-2-(4-(2-chloropyridin-3-yl)phenyl)-3-methylquinoline-4-carboxylic acid
-
-
6-chloro-2-(4-(2-fluoropyridin-3-yl)phenyl)-3-methylquinoline-4-carboxylic acid
-
-
6-fluoro-2-(2'-fluoro[1,1'-biphenyl]-4-yl)-3-methylquinoline-4-carboxylic acid
-
6-fluoro-2-(4-(2-fluoro-6-methylpyridin-3-yl)phenyl)-3-methylquinoline-4-carboxylic acid
-
-
6-fluoro-2-(4-(2-fluoropyridin-3-yl)phenyl)-3-methylquinoline-4-carboxylic acid
-
-
isolapachol
8.3fold selectivity for Schistosoma mansoni over human enzyme
-
methyl 2-(4-(4-(trifluoromethyl)pyridin-3-yl)phenyl)quinoline-4-carboxylate
-
-
[[3-(3-methylbut-2-en-1-yl)-1,4-dioxo-1,4-dihydronaphthalen-2-yl]oxy]acetonitrile
-
-
(1-(5-cyclopropylpyrimidin-2-yl)-3-isopropoxy-5-methyl-1H-pyrazol-4-yl)(phenyl)methanol
Q02172
-
(2E)-2-cyano-3-hydroxy-N-[4-(trifluoromethyl)phenyl]but-2-enamide
-
50% inhibition at 0.000435 mM
1-(2-((4-bromo-3-(trifluoromethyl)phenyl)amino)-4-methylthiazol-5-yl)ethanone
Q02172
-
1-(2-((4-chloro-3-(trifluoromethyl)phenyl)amino)-4-methylthiazol-5-yl)ethanone
Q02172
-
2-(3-ethoxy-4-(2-fluorophenoxy)-5-methyl-1H-pyrazol-1-yl)-5-ethylpyrimidine
Q02172
-
2-(3-ethoxy-5-methyl-4-(2-(trifluoromethyl)phenoxy)-1H-pyrazol-1-yl)-5-ethylpyrimidine
Q02172
-
2-(3-ethoxy-5-methyl-4-(3-(trifluoromethyl)phenoxy)-1H-pyrazol-1-yl)-5-ethylpyrimidine
Q02172
-
2-(3-ethoxy-5-methyl-4-(4-(trifluoromethyl)phenoxy)-1H-pyrazol-1-yl)-5-ethylpyrimidine
Q02172
-
2-(4'-tert-butyl-2-chloro-biphenyl-4-ylcarbamoyl)-cyclopent-1-enecarboxylic acid
-
50% inhibition at 0.000080 mM
2-(4-(2,3-dichlorophenoxy)-3-ethoxy-5-methyl-1H-pyrazol-1-yl)-5-ethylpyrimidine
Q02172
-
2-(4-(2,3-difluorophenoxy)-3-isopropoxy-5-methyl-1H-pyrazol-1-yl)-5-ethylpyrimidine
Q02172
-
2-(4-(2,4-difluorophenoxy)-3-isopropoxy-5-methyl-1H-pyrazol-1-yl)-5-ethylpyrimidine
Q02172
-
2-(4-(2,5-dichlorophenoxy)-3-ethoxy-5-methyl-1H-pyrazol-1-yl)-5-ethylpyrimidine
Q02172
-
2-(4-(2,5-difluorophenoxy)-3-isopropoxy-5-methyl-1H-pyrazol-1-yl)-5-ethylpyrimidine
Q02172
-
2-(4-(2,6-difluorophenoxy)-3-isopropoxy-5-methyl-1H-pyrazol-1-yl)-5-ethylpyrimidin-4-ol
Q02172
-
2-(4-(2,6-difluorophenoxy)-3-isopropoxy-5-methyl-1H-pyrazol-1-yl)-5-ethylpyrimidine
Q02172
-
2-(4-(2,6-difluorophenoxy)-3-isopropoxy-5-methyl-1H-pyrazol-1-yl)-5-fluoropyrimidine
Q02172
-
2-(4-(2,6-difluorophenoxy)-3-isopropoxy-5-methyl-1H-pyrazol-1-yl)-5-methoxypyrimidine
Q02172
-
2-(4-(2,6-difluorophenoxy)-3-isopropoxy-5-methyl-1H-pyrazol-1-yl)-5-methylpyrimidin-4-ol
Q02172
-
2-(4-(2,6-difluorophenoxy)-3-isopropoxy-5-methyl-1H-pyrazol-1-yl)-5-propylpyrimidin-4-ol
Q02172
-
2-(4-(2,6-difluorophenoxy)-3-isopropoxy-5-methyl-1H-pyrazol-1-yl)-5-propylpyrimidine
Q02172
-
2-(4-(2,6-difluorophenoxy)-3-isopropoxy-5-methyl-1H-pyrazol-1-yl)-pyrimidine
Q02172
-
2-(4-(2,6-difluorophenoxy)-3-isopropoxy-5-methyl-1H-pyrazol-1-yl)pyrimidin-4-ol
Q02172
-
2-(4-(2-bromophenoxy)-3-ethoxy-5-methyl-1H-pyrazol-1-yl)-5-ethylpyrimidine
Q02172
-
2-(4-(2-chlorophenoxy)-3-ethoxy-5-methyl-1H-pyrazol-1-yl)-5-ethylpyrimidine
Q02172
-
2-(4-(3,5-dichlorophenoxy)-3-ethoxy-5-methyl-1H-pyrazol-1-yl)-5-ethylpyrimidine
Q02172
-
2-(4-benzyl-1-(5-ethylpyrimidin-2-yl)-5-methyl-1H-pyrazol-3-yloxy)ethanol
Q02172
-
2-(4-benzyl-3-(2-(benzyloxy)ethoxy)-5-methyl-1H-pyrazol-1-yl)-5-ethylpyrimidine
Q02172
-
2-(4-benzyl-3-isopropoxy-5-methyl-1H-pyrazol-1-yl)-5-cyclopropylpyrimidine
Q02172
-
2-(4-benzyl-3-methoxy-5-methyl-1H-pyrazol-1-yl)-5-cyclopropylpyrimidine
Q02172
-
2-(4-benzyl-3-sec-butoxy-5-methyl-1H-pyrazol-1-yl)-5-cyclopropylpyrimidine
Q02172
-
2-(4-benzyl-5-methyl-3-(pentan-3-yloxy)-1H-pyrazol-1-yl)-5-cyclopropylpyrimidine
Q02172
-
2-([[2,3,5,6-tetrafluoro-3'-(trifluoromethoxy)biphenyl-4-yl]amino]carbonyl)cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.000007 mM
2-([[2-chloro-3'-(trifluoromethoxy)biphenyl-4-yl]amino]carbonyl)cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.000020 mM
2-([[2-chloro-4'-(dimethylamino)biphenyl-4-yl]amino]carbonyl)cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.00005 mM
2-([[3'-(trifluoromethoxy)-3-(trifluoromethyl)biphenyl-4-yl]amino]carbonyl)cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.000840 mM
2-([[3,5-difluoro-3'-(trifluoromethoxy)biphenyl-4-yl]amino]carbonyl)cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.000033 mM
2-([[3-chloro-3'-(trifluoromethoxy)biphenyl-4-yl]amino]carbonyl)cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.000290 mM
2-([[3-cyano-3'-(trifluoromethoxy)biphenyl-4-yl]amino]carbonyl)cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.000370 mM
2-([[3-fluoro-3'-(trifluoromethoxy)biphenyl-4-yl]amino]carbonyl)cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.00028 mM
2-([[3-fluoro-4'-(trifluoromethoxy)biphenyl-4-yl]amino]carbonyl)cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.00570 mM
2-([[3-methyl-3'-(trifluoromethoxy)biphenyl-4-yl]amino]carbonyl)cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.000150 mM
2-([[3-nitro-3'-(trifluoromethoxy)biphenyl-4-yl]amino]carbonyl)cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.000390 mM
2-([[4'-(dimethylamino)-3,5-difluorobiphenyl-4-yl]amino]carbonyl)cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.00061 mM
2-([[4-(1-naphthyl)-2-(trifluoromethyl)phenyl]amino]carbonyl)cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.000180 mM
2-cyano-3-(9-ethyl-9H-carbazol-3-ylamino)acrylic acid ethyl ester
-
IC50: 0.491 mM
2-cyano-3-cyclopropyl-3-hydroxy-N-[4'-(cyano)phenyl]-propenamide
-
50% inhibition at 0.0.00035 mM, N-terminally truncated protein
2-cyano-3-cyclopropyl-3-hydroxy-N-[4'-(nitro)phenyl]-propenamide
-
50% inhibition at 0.00025 mM, N-terminally truncated protein
2-cyano-3-cyclopropyl-3-hydroxy-N-[4'-(trifluoromethyl)phenyl]-propenamide
-
50% inhibition at 0.00019 mM, N-terminally truncated protein
2-[(biphenyl-4-ylamino)carbonyl]cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.00041 mM
2-[[(2',3,5-trifluorobiphenyl-4-yl)amino]carbonyl]cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.000045 mM
2-[[(2'-chloro-3,5-difluorobiphenyl-4-yl)amino]carbonyl]cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.000018 mM
2-[[(2'-chlorobiphenyl-4-yl)amino]carbonyl]cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.000225 mM
2-[[(2,3,5,6-tetrafluoro-2'-methoxybiphenyl-4-yl)amino]carbonyl]cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.000008 mM
2-[[(3'-ethoxy-3,5-difluorobiphenyl-4-yl)amino]carbonyl]cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.000017 mM
2-[[(3,3'-dimethoxybiphenyl-4-yl)amino]carbonyl]cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.000170 mM
2-[[(3,5-difluoro-2',4'-dimethoxybiphenyl-4-yl)amino]carbonyl]cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.000090 mM
2-[[(3,5-difluoro-2'-methoxybiphenyl-4-yl)amino]carbonyl]cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.000042 mM
2-[[(3-chloro-2'-methoxybiphenyl-4-yl)amino]carbonyl]cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.000310 mM
2-[[(3-chloro-4'-methoxybiphenyl-4-yl)amino]carbonyl]cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.00840 mM
2-[[(3-fluoro-3'-hydroxybiphenyl-4-yl)amino]carbonyl]cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.000610 mM
2-[[(3-fluoro-4'-methoxybiphenyl-4-yl)amino]carbonyl]cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.00170 mM
2-[[(4'-bromo-2-chlorobiphenyl-4-yl)amino]carbonyl]cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.000070 mM
2-[[(4'-bromo-3-chlorobiphenyl-4-yl)amino]carbonyl]cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.002900 mM
2-[[(4'-bromo-3-fluorobiphenyl-4-yl)amino]carbonyl]cyclopent-1-ene-1-carboxylic acid
-
50% inhibition at 0.000735 mM
3-(4-benzyl-1-(5-ethylpyrimidin-2-yl)-5-methyl-1H-pyrazol-3-yloxy)-N,N-dimethylpropan-1-amine
Q02172
-
3-hydroxy-2-(3,3-dichloroallyl)-1,4-naphthoquinone
-
50% inhibition at 0.000065 mM, i. e. dichloroallyl lawsone, N-terminally truncated protein
5-bromo-2-(4-(2,6-difluorophenoxy)-3-isopropoxy-5-methyl-1H-pyrazol-1-yl)pyrimidine
Q02172
-
5-cyclopropyl-2-(4-(2,6-difluorophenoxy)-3-isopropoxy-5-methyl-1H-pyrazol-1-yl)pyrimidine
Q02172
-
5-cyclopropyl-2-(4-(2-fluorobenzyl)-3-isopropoxy-5-methyl-1H-pyrazol-1-yl)pyrimidine
Q02172
-
5-ethyl-2-(3-isopropoxy-4-(2-methoxybenzyl)-5-methyl-1H-pyrazol-1-yl)pyrimidine
Q02172
-
5-ethyl-2-(3-isopropoxy-4-(3-methoxybenzyl)-5-methyl-1H-pyrazol-1-yl)pyrimidine
Q02172
-
5-ethyl-2-(3-isopropoxy-4-(4-methoxybenzyl)-5-methyl-1H-pyrazol-1-yl)pyrimidine
Q02172
-
5-ethyl-2-(4-(2-fluorobenzyl)-3-isopropoxy-5-methyl-1H-pyrazol-1-yl)pyrimidine
Q02172
-
5-ethyl-2-(4-(2-fluorophenoxy)-3-isopropoxy-5-methyl-1H-pyrazol-1-yl)pyrimidine
Q02172
-
5-ethyl-2-(4-(3-fluorobenzyl)-3-isopropoxy-5-methyl-1H-pyrazol-1-yl)pyrimidine
Q02172
-
5-ethyl-2-(4-(3-fluorophenoxy)-3-isopropoxy-5-methyl-1H-pyrazol-1-yl)pyrimidine
Q02172
-
5-ethyl-2-(4-(4-fluorobenzyl)-3-isopropoxy-5-methyl-1H-pyrazol-1-yl)pyrimidine
Q02172
-
5-ethyl-2-(4-(4-fluorophenoxy)-3-isopropoxy-5-methyl-1H-pyrazol-1-yl)pyrimidine
Q02172
-
5-methyl-2-(4-(2,6-difluorophenoxy)-3-isopropoxy-5-methyl-1H-pyrazol-1-yl)pyrimidine
Q02172
-
5-methyl-N-[4-(trifluoromethyl)phenyl][1,2,4]triazolo[1,5-a]pyrimidin-7-amine
-
-
ethyl 2-((2,3-dihydro-1h-inden-5-yl)amino)-4-phenylthiazole-5-carboxylate
Q02172
-
ethyl 2-((3'-methoxy-[1,1'-biphenyl]-4-yl)amino)-4-phenylthiazole-5-carboxylate
Q02172
-
ethyl 2-((3,5-difluoro-3'-methoxy-[1,1'-biphenyl]-4-yl)-amino)-4-phenylthiazole-5-carboxylate
Q02172
-
ethyl 2-((3-chloro-4-((2-chloro-6-fluorobenzyl)oxy)phenyl)-amino)-4-phenylthiazole-5-carboxylate
Q02172
-
ethyl 2-((3-chloro-4-methylphenyl)amino)-4-cyclopropylthiazole-5-carboxylate
Q02172
-
ethyl 2-((3-chloro-4-methylphenyl)amino)-4-methylthiazole-5-carboxylate
Q02172
-
ethyl 2-((3-chloro-4-methylphenyl)amino)-4-phenylthiazole-5-carboxylate
Q02172
-
ethyl 2-((3-chloro-4-phenoxyphenyl)amino)-4-phenylthiazole-5-carboxylate
Q02172
-
ethyl 2-((3-fluoro-3'-methoxy-[1,1'-biphenyl]-4-yl)amino)-4-phenylthiazole-5-carboxylate
Q02172
-
ethyl 2-((3-fluoro-4-methylphenyl)amino)-4-methylthiazole-5-carboxylate
Q02172
-
ethyl 2-((3-fluoro-4-methylphenyl)amino)-4-phenylthiazole-5-carboxylate
Q02172
-
ethyl 2-((3-fluoro-[1,1'-biphenyl]-4-yl)amino)-4-phenylthiazole-5-carboxylate
Q02172
-
ethyl 2-((4-(benzyloxy)-3-chlorophenyl)amino)-4-phenylthiazole-5-carboxylate
Q02172
-
ethyl 2-((4-bromo-3-(trifluoromethyl)phenyl)amino)-4-phenylthiazole-5-carboxylate
Q02172
-
ethyl 2-((4-chloro-3-(trifluoromethyl)phenyl)amino)-4-(cyclopropanecarboxamido)thiazole-5-carboxylate
Q02172
-
ethyl 2-((4-chloro-3-(trifluoromethyl)phenyl)amino)-4-phenylthiazole-5-carboxylate
Q02172
-
ethyl 4-(cyclopropanecarboxamido)-2-((3,4-dimethylphenyl)amino)thiazole-5-carboxylate
Q02172
-
ethyl 4-(tert-butyl)-2-((3,4-dimethylphenyl)amino)thiazole-5-carboxylate
Q02172
-
ethyl 4-(tert-butyl)-2-((3-chloro-4-methylphenyl)amino)-thiazole-5-carboxylate
Q02172
-
ethyl 4-(tert-butyl)-2-((3-fluoro-4-methylphenyl)amino)-thiazole-5-carboxylate
Q02172
-
ethyl 4-amino-2-((4-chloro-3-(trifluoromethyl)phenyl)-amino)thiazole-5-carboxylate
Q02172
-
ethyl 4-benzamido-2-((4-chloro-3-(trifluoromethyl)phenyl)-amino)thiazole-5-carboxylate
Q02172
-
ethyl 4-cyclopropyl-2-((3,4-dimethylphenyl)amino)thiazole-5-carboxylate
Q02172
-
ethyl 4-cyclopropyl-2-((4-fluoro-3-methylphenyl)amino)-thiazole-5-carboxylate
Q02172
-
ethyl 4-phenyl-2-((4-(trifluoromethyl)phenyl)amino)-thiazole-5-carboxylate
Q02172
-
ethyl 4-phenyl-2-((5,6,7,8-tetrahydronaphthalen-2-yl)-amino)thiazole-5-carboxylate
Q02172
-
N-[3-fluoro-4-(trifluoromethyl)phenyl]-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
-
-
[2-fluoro-2',5'-dimethyl-4'-[6-(3-methyl-2-butenyloxy)pyridin-3-yl]biphenyl-4-yl]-(3-methyl-2-butenyl)amine
-
i.e. S-2678, suppresses immunoglobulin production in human peripheral blood mononuclear cells in vitro, with little or no inhibition of cell proliferation
6-fluoro-2-[2-methyl-4-phenoxy-5-(propan-2-yl)phenyl]quinoline-4-carboxylic acid
-
-
6-fluoro-2-[2-methyl-4-phenoxy-5-(propan-2-yl)phenyl]quinoline-4-carboxylic acid
i.e. C44
-
teriflunomide
160fold selectivity for human over Schistosoma mansoni enzyme
2-hydroxyethylidene-cyanoacetic acid 4-trifluoromethyl anilide
-
A77 1726, active metabolite of leflumonide
2-hydroxyethylidene-cyanoacetic acid 4-trifluoromethyl anilide
-
anti-proliferative effect of A77 1726 is mediated by inhibition of enzyme
2-hydroxyethylidene-cyanoacetic acid 4-trifluoromethyl anilide
-
inbibits by interference with the transfer of electrons from flavin to quinone
2-hydroxyethylidene-cyanoacetic acid 4-trifluoromethyl anilide
-
noncompetitive versus ubiquinone, uncompetitive versus dihydroorotate, study of kinetics
A77 1726
-
inhibits cell growth in multiple myeloma cell lines at clinically achievable concentrations by induction of apoptosis. Inhibition of cell growth is partly due to inhibition of multiple myeloma cell proliferation. A77 1726 shows synergistic and additive activity together with genotoxic agents melphalan, treosulfan, and doxorubicin
brequinar sodium
-
tight binding, most potent inhibitor, mutant H26A is insensitive, wild-type and other mutants are inhibited by 50% at concentrations between 6 and 10 nM
brequinar sodium
-
inbibits by interference with the transfer of electrons from flavin to quinone
brequinar sodium
-
competitive versus ubiquinone, uncompetitive versus dihydroorotate, study of kinetics
additional information
competitive nature of small molecule inhibitors toward the putative ubiquinone binding site
-
additional information
-
competitive nature of small molecule inhibitors toward the putative ubiquinone binding site
-
additional information
synthesis of a series of 2-substituted quinoline-4-carboxylic acids by Doebner reaction starting from freely available protocatechuic aldehyde and vanillin precursors. Human dihydroorotate dehydrogenase (hDHODH) is recognised as a clear molecular target for these heterocycles. All compounds are also tested for their antiproliferative potential against three cancer cells (MCF-7, A549, A375) and one normal cell line (HaCaT) to evaluate the selective cytotoxicity, overview. IC50 for cytotoxicity in in vivo assays. Molecular docking studies
-
additional information
-
synthesis of a series of 2-substituted quinoline-4-carboxylic acids by Doebner reaction starting from freely available protocatechuic aldehyde and vanillin precursors. Human dihydroorotate dehydrogenase (hDHODH) is recognised as a clear molecular target for these heterocycles. All compounds are also tested for their antiproliferative potential against three cancer cells (MCF-7, A549, A375) and one normal cell line (HaCaT) to evaluate the selective cytotoxicity, overview. IC50 for cytotoxicity in in vivo assays. Molecular docking studies
-
additional information
two potential residues, T63 and Y356, suitable for H-bonding interactions, are identified in the brequinar-binding pocket, design, synthesis, and biological evaluation of 4-quinoline carboxylic acids as inhibitors of dihydroorotate dehydrogenase, overview. Cytotoxicity and bioavalability assays using HCT-116 and MIA PaCa-2 canvcer cells
-
additional information
-
DHODH-specific inhibitors with low nanomolar binding affinities bind in the N-terminal hydrophobic channel of dihydroorotate dehydrogenase, the presumed site of ubiquinone binding during oxidation of dihydroorotate to orotate
-
additional information
-
screening for potent inhibitors of PfDHODH and effect on the human enzyme, overview. The compiunds show strong selectivity for the malarial enzyme over that from the human host, inhibition mechanism, overview
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
relative Km-values for wild-type and mutants listed for (S)-dihydroorotate and ubiquinone-6
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
relative turnover numbers for wild-type and mutants listed for (S)-dihydroorotate and ubiquinone6
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0002 - 0.0009
2-hydroxyethylidene-cyanoacetic acid 4-trifluoromethyl anilide
-
competitive to dihydroorotate
0.0002 - 0.0009
2-hydroxyethylidene-cyanoacetic acid 4-trifluoromethyl anilide
-
competitive to ubiquinone, non-competitive to dihydroorotate, parent compound leflunomide has no inhibitory effect at concentrations up to 0.001 mM
0.001
2-hydroxyethylidene-cyanoacetic acid 4-trifluoromethyl anilide
-
non-competitive to decyclubiquinone
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000117
(2Z)-2-cyano-3-cyclopropyl-3-hydroxy-N-[4-(trifluoromethyl)phenyl]prop-2-enamide
Homo sapiens
-
-
0.00018
(2Z)-2-cyano-N-(2',3-dichlorobiphenyl-4-yl)-3-hydroxybut-2-enamide
Homo sapiens
-
-
0.000022
(2Z)-2-cyano-N-(2,2'-dichlorobiphenyl-4-yl)-3-hydroxybut-2-enamide
Homo sapiens
-
-
0.00019
(2Z)-2-cyano-N-(2,3'-dichlorobiphenyl-4-yl)-3-hydroxybut-2-enamide
Homo sapiens
-
-
0.00013
(2Z)-2-cyano-N-(3'-ethoxybiphenyl-4-yl)-3-hydroxybut-2-enamide, (2Z)-N-(2'-chlorobiphenyl-4-yl)-2-cyano-3-hydroxybut-2-enamide
Homo sapiens
-
-
0.0002
(2Z)-N-(3-chloro-2'-methoxybiphenyl-4-yl)-2-cyano-3-hydroxybut-2-enamide
Homo sapiens
-
-
0.00017
(2Z)-N-[2'-chloro-3-(trifluoromethyl)biphenyl-4-yl]-2-cyano-3-hydroxybut-2-enamide
Homo sapiens
-
-
0.007
2-(1,1-difluoroethyl)-5-methyl-N-[4-(pentafluoro-lambda6-sulfanyl)phenyl][1,2,4]triazolo[1,5-a]pyrimidin-7-amine
Homo sapiens
pH 8.2, 25°C
-
0.0000118
2-(2'-fluoro-[1,1'-biphenyl]-4-yl)-3-methyl-6-(trifluoromethyl)-1,7-naphthyridine-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
0.000127
2-(2'-methoxy-[1,1'-biphenyl]-4-yl)quinoline-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
0.268
2-(2,3-bis(benzyloxy)phenyl)quinoline-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
0.000123
2-(2,3-dichloroanilino)-3-hydroxynaphthalene-1,4-dione
Homo sapiens
pH 8.2, 25°C
-
0.34
2-(2,4-bis(benzyloxy)phenyl)quinoline-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
0.01
2-(2,6-dimethylanilino)-3-hydroxynaphthalene-1,4-dione
Homo sapiens
pH 8.2, 25°C
-
0.000808
2-(2-chloroanilino)-3-hydroxynaphthalene-1,4-dione
Homo sapiens
pH 8.2, 25°C
-
0.27
2-(3,4-bis(benzyloxy)phenyl)quinoline-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
0.148
2-(3,4-diisobutoxyphenyl)quinoline-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
0.000911
2-(3-chloroanilino)-3-hydroxynaphthalene-1,4-dione
Homo sapiens
pH 8.2, 25°C
-
0.449
2-(3-methoxy-4-propoxyphenyl)quinoline-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
0.0084
2-(4-(1H-imidazol-1-yl)phenyl)quinoline-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
0.000148
2-(4-(2-(trifluoromethyl)pyridin-3-yl)phenyl)quinoline-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
0.00526
2-(4-(2-chloro-6-methylpyridin-3-yl)phenyl)-3-methyl-1,7-naphthyridine-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
0.000184
2-(4-(2-chloro-6-methylpyridin-3-yl)phenyl)-3-methylquinoline-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
0.0000262
2-(4-(2-chloro-6-methylpyridin-3-yl)phenyl)-6-fluoro-3-methylquinoline-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
0.000235
2-(4-(2-chloro-6-methylpyridin-3-yl)phenyl)quinoline-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
0.0000542
2-(4-(2-chloropyridin-3-yl)phenyl)-3,6-dimethylquinoline-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
0.000259
2-(4-(2-chloropyridin-3-yl)phenyl)-3-methyl-1,7-naphthyridine-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
0.000201
2-(4-(2-chloropyridin-3-yl)phenyl)-3-methyl-6-(trifluoromethyl)-1,7-naphthyridine-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
0.0000543
2-(4-(2-chloropyridin-3-yl)phenyl)-3-methylquinoline-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
0.00000971
2-(4-(2-chloropyridin-3-yl)phenyl)-6-fluoro-3-methylquinoline-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
0.0000327
2-(4-(2-chloropyridin-3-yl)phenyl)quinoline-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
0.00248
2-(4-(2-fluoro-6-methylpyridin-3-yl)phenyl)-3-methylquinoline-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
0.000504
2-(4-(2-fluoropyridin-3-yl)phenyl)-3-methylquinoline-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
0.00142
2-(4-(2-fluoropyridin-3-yl)phenyl)quinoline-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
0.000165
2-(4-(2-methoxypyridin-3-yl)phenyl)quinoline-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
0.0000221
2-(4-(2-methylpyridin-3-yl)phenyl)quinoline-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
0.00143
2-(4-(4-(trifluoromethyl)pyridin-3-yl)phenyl)quinoline-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
0.000373
2-(4-(4-methylpyridin-3-yl)phenyl)quinoline-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
0.0125
2-(4-(6-fluoropyridin-3-yl)phenyl)quinoline-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
0.467
2-(4-(benzyloxy)-3-methoxyphenyl)quinoline-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
0.00807
2-(4-(piperidin-1-yl)phenyl)quinoline-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
0.0101
2-(4-(pyridin-2-yl)phenyl)quinoline-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
0.000391
2-(4-(pyridin-3-yl)phenyl)quinoline-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
0.00755
2-(4-(pyridin-4-yl)phenyl)quinoline-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
0.2
2-(4-(pyrimidin-2-yl)phenyl)quinoline-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
0.34
2-(4-butoxy-3-methoxyphenyl)quinoline-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
0.000541
2-(4-chloroanilino)-3-hydroxynaphthalene-1,4-dione
Homo sapiens
pH 8.2, 25°C
-
0.00033
2-(4-fluoroanilino)-3-hydroxynaphthalene-1,4-dione
Homo sapiens
pH 8.2, 25°C
-
0.944
2-(4-hydroxy-3-methoxyphenyl)quinoline-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
0.438
2-(4-isobutoxy-3-methoxyphenyl)quinoline-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
0.00279
2-([1,1'-biphenyl]-4-yl)-3-methyl-1,6-naphthyridine-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
0.0000283
2-([1,1'-biphenyl]-4-yl)-3-methyl-1,7-naphthyridine-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
0.00122
2-([1,1'-biphenyl]-4-yl)-3-methyl-1,8-naphthyridine-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
0.0000212
2-([1,1'-biphenyl]-4-yl)-3-methyl-6-(trifluoromethyl)-1,7-naphthyridine-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
0.0000754
2-([1,1'-biphenyl]-4-yl)-3-methylquinoline-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
0.000051
2-([1,1'-biphenyl]-4-yl)quinoline-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
0.0068
2-hydroxy-3-(4-phenylpiperazin-1-yl)naphthalene-1,4-dione
Homo sapiens
pH 8.2, 25°C
-
0.000108
2-hydroxy-3-[3-(trifluoromethyl)anilino]naphthalene-1,4-dione
Homo sapiens
pH 8.2, 25°C
-
0.00105
2-[(2,3-dihydro-1,4-benzodioxin-6-yl)amino]-3-hydroxynaphthalene-1,4-dione
Homo sapiens
pH 8.2, 25°C
-
0.000013
2-[(2,5-dichlorophenyl)sulfanyl]-5-ethyl[1,2,4]triazolo[1,5-a]pyrimidin-7-ol
Homo sapiens
or above, pH not specified in the publication, temperature not specified in the publication
0.000051
2-[(2,5-dichlorophenyl)sulfanyl]-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-ol
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
0.0036
2-[(2H-1,3-benzodioxol-5-yl)amino]-3-hydroxynaphthalene-1,4-dione
Homo sapiens
pH 8.2, 25°C
-
0.0065
2-[(3,4-dichlorophenyl)sulfanyl]-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-ol
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
0.039
2-[(4-chlorophenyl)sulfanyl]-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-ol
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
0.0018
2-[4-(2,3-dichlorophenyl)piperazin-1-yl]-3-hydroxynaphthalene-1,4-dione
Homo sapiens
pH 8.2, 25°C
-
0.0046
2-[4-(4-chlorophenyl)piperazin-1-yl]-3-hydroxynaphthalene-1,4-dione
Homo sapiens
pH 8.2, 25°C
-
0.0079
3-(3-methylbut-2-en-1-yl)-1,4-dioxo-1,4-dihydronaphthalen-2-yl 4-methylbenzene-1-sulfonate
Homo sapiens
pH 8.2, 25°C
-
0.000015
6-chloro-2-(2'-fluorobiphenyl-4-yl)quinoline-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
0.0000744
6-chloro-2-(4-(2-chloro-6-methylpyridin-3-yl)phenyl)-3-methylquinoline-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
0.000036
6-chloro-2-(4-(2-chloropyridin-3-yl)phenyl)-3-methylquinoline-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
0.000165
6-chloro-2-(4-(2-fluoropyridin-3-yl)phenyl)-3-methylquinoline-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
0.00331
6-fluoro-2-(4-(2-fluoro-6-methylpyridin-3-yl)phenyl)-3-methylquinoline-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
0.0000794
6-fluoro-2-(4-(2-fluoropyridin-3-yl)phenyl)-3-methylquinoline-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
0.05
methyl 2-(4-(4-(trifluoromethyl)pyridin-3-yl)phenyl)quinoline-4-carboxylate
Homo sapiens
pH 8.0, 22°C
-
0.2
methyl 2-(4-(piperidin-1-yl)phenyl)quinoline-4-carboxylate, methyl 2-(4-(pyridin-3-yl)phenyl)quinoline-4-carboxylate, methyl 2-(4-cyclohexylphenyl)quinoline-4-carboxylate, methyl 2-([1,1'-biphenyl]-4-yl)quinoline-4-carboxylate
Homo sapiens
pH 8.0, 22°C
-
0.00385
1-(2-((3,4-dimethylphenyl)amino)-4-methylthiazol-5-yl)-ethanone
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.00394
1-(2-((3-chloro-4-methylphenyl)amino)-4-methylthiazol-5-yl)ethanone
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.01
1-(2-((3-fluoro-4-methylphenyl)amino)-4-methylthiazol-5-yl)ethanone
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.00365
1-(2-((4-(tert-butyl)phenyl)amino)-4-methylthiazol-5-yl)-ethanone
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.00193
1-(2-((4-bromo-3-(trifluoromethyl)phenyl)amino)-4-methylthiazol-5-yl)ethanone
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.01
1-(2-((4-bromophenyl)amino)-4-methylthiazol-5-yl)-ethanone
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.00235
1-(2-((4-chloro-3-(trifluoromethyl)phenyl)amino)-4-methylthiazol-5-yl)ethanone
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.01
1-(2-(anthracen-2-ylamino)-4-methylthiazol-5-yl)ethan-1-one
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.11
1-(2-methoxyphenyl)-3-naphthalen-1-ylurea
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.000562
1-(4-methyl-2-(naphthalen-2-ylamino)thiazol-5-yl)ethan-1-one
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.491
2-cyano-3-(9-ethyl-9H-carbazol-3-ylamino)acrylic acid ethyl ester
Homo sapiens
-
IC50: 0.491 mM
0.03
2-[(E)-2-(2-methylphenyl)ethenyl]quinolin-4-ol
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.03
4-pentyl-1,3,4,10-tetrahydroacridin-9(2H)-one
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.00047
5-(1H-benzimidazol-1-yl)-N-propylthiophene-2-carboxamide
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.00071
5-(1H-indol-1-yl)-N-propylthiophene-2-carboxamide
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.00063
5-(2-methyl-1H-benzimidazol-1-yl)-N-propylthiophene-2-carboxamide
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.03
5-(2-methyl-1H-indol-1-yl)-N-propylthiophene-2-carboxamide
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.01
5-(4-methylpiperazin-1-yl)-N-propylthiophene-2-carboxamide
Homo sapiens
-
above, pH not specified in the publication, temperature not specified in the publication
0.01
5-(piperidin-1-yl)-N-propylthiophene-2-carboxamide
Homo sapiens
-
above, pH not specified in the publication, temperature not specified in the publication
0.2
5-methyl-N-(naphthalen-2-yl)[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.00029
5-methyl-N-[4-(trifluoromethyl)phenyl][1,2,4]triazolo[1,5-a]pyrimidin-7-amine
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.03
diethyl [(dibenzo[b,d]thiophen-2-ylamino)methylidene]propanedioate
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.000026
ethyl 2-((2,3-dihydro-1h-inden-5-yl)amino)-4-phenylthiazole-5-carboxylate
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.01
ethyl 2-((3'-methoxy-[1,1'-biphenyl]-4-yl)amino)-4-phenylthiazole-5-carboxylate
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.000174
ethyl 2-((3,4-dichlorophenyl)amino)-4-phenylthiazole-5-carboxylate
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.001358
ethyl 2-((3,4-dimethylphenyl)amino)-4-methylthiazole-5-carboxylate
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.000058
ethyl 2-((3,4-dimethylphenyl)amino)-4-phenylthiazole-5-carboxylate
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.000393
ethyl 2-((3,5-dichlorophenyl)amino)-4-phenylthiazole-5-carboxylate
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.000311
ethyl 2-((3,5-difluoro-3'-methoxy-[1,1'-biphenyl]-4-yl)-amino)-4-phenylthiazole-5-carboxylate
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.01
ethyl 2-((3-chloro-4-((2-chloro-6-fluorobenzyl)oxy)phenyl)-amino)-4-phenylthiazole-5-carboxylate
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.000372
ethyl 2-((3-chloro-4-methylphenyl)amino)-4-cyclopropylthiazole-5-carboxylate
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.000969
ethyl 2-((3-chloro-4-methylphenyl)amino)-4-methylthiazole-5-carboxylate
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.000035
ethyl 2-((3-chloro-4-methylphenyl)amino)-4-phenylthiazole-5-carboxylate
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.01
ethyl 2-((3-chloro-4-phenoxyphenyl)amino)-4-phenylthiazole-5-carboxylate
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.01
ethyl 2-((3-fluoro-3'-methoxy-[1,1'-biphenyl]-4-yl)amino)-4-phenylthiazole-5-carboxylate
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.001987
ethyl 2-((3-fluoro-4-methylphenyl)amino)-4-methylthiazole-5-carboxylate
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.000049
ethyl 2-((3-fluoro-4-methylphenyl)amino)-4-phenylthiazole-5-carboxylate
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.01
ethyl 2-((3-fluoro-[1,1'-biphenyl]-4-yl)amino)-4-phenylthiazole-5-carboxylate
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.01
ethyl 2-((4-(benzyloxy)-3-chlorophenyl)amino)-4-phenylthiazole-5-carboxylate
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.000284
ethyl 2-((4-(tert-butyl)phenyl)amino)-4-phenylthiazole-5-carboxylate
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.01
ethyl 2-((4-bromo-2-methylphenyl)amino)-4-phenylthiazole-5-carboxylate
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.000128
ethyl 2-((4-bromo-3-(trifluoromethyl)phenyl)amino)-4-phenylthiazole-5-carboxylate
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.00907
ethyl 2-((4-bromophenyl)amino)-4-methylthiazole-5-carboxylate
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.00604
ethyl 2-((4-chloro-3-(trifluoromethyl)phenyl)amino)-4-(cyclopropanecarboxamido)thiazole-5-carboxylate
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.000131
ethyl 2-((4-chloro-3-(trifluoromethyl)phenyl)amino)-4-phenylthiazole-5-carboxylate
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.000239
ethyl 2-((4-chlorophenyl)amino)-4-phenylthiazole-5-carboxylate
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.00144
ethyl 2-((4-methoxyphenyl)amino)-4-phenylthiazole-5-carboxylate
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.000453
ethyl 2-(anthracen-2-ylamino)-4-phenylthiazole-5-carboxylate
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.001108
ethyl 2-(benzo[d][1,3]dioxol-5-ylamino)-4-phenylthiazole-5-carboxylate
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.000029
ethyl 2-(naphthalen-2-ylamino)-4-phenylthiazole-5-carboxylate
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.01
ethyl 2-([1,1'-biphenyl]-4-ylamino)-4-phenylthiazole-5-carboxylate
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.03
ethyl 4-(4-ethoxybenzyl)-3,5-dimethyl-1H-pyrrole-2-carboxylate
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.01
ethyl 4-(cyclopropanecarboxamido)-2-((3,4-dimethylphenyl)amino)thiazole-5-carboxylate
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.000515
ethyl 4-(tert-butyl)-2-((3,4-dimethylphenyl)amino)thiazole-5-carboxylate
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.000552
ethyl 4-(tert-butyl)-2-((3-chloro-4-methylphenyl)amino)-thiazole-5-carboxylate
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.000652
ethyl 4-(tert-butyl)-2-((3-fluoro-4-methylphenyl)amino)-thiazole-5-carboxylate
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.00211
ethyl 4-amino-2-((3,4-dimethylphenyl)amino)thiazole-5-carboxylate
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.01
ethyl 4-amino-2-((4-chloro-3-(trifluoromethyl)phenyl)-amino)thiazole-5-carboxylate
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.00903
ethyl 4-benzamido-2-((3,4-dimethylphenyl)amino)thiazole-5-carboxylate
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.01
ethyl 4-benzamido-2-((4-chloro-3-(trifluoromethyl)phenyl)-amino)thiazole-5-carboxylate
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.000325
ethyl 4-cyclopropyl-2-((3,4-dimethylphenyl)amino)thiazole-5-carboxylate
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.000645
ethyl 4-cyclopropyl-2-((4-fluoro-3-methylphenyl)amino)-thiazole-5-carboxylate
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.000887
ethyl 4-methyl-2-(naphthalen-2-ylamino)thiazole-5-carboxylate
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.000408
ethyl 4-phenyl-2-((4-(trifluoromethyl)phenyl)amino)-thiazole-5-carboxylate
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.000018
ethyl 4-phenyl-2-((5,6,7,8-tetrahydronaphthalen-2-yl)-amino)thiazole-5-carboxylate
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.000784
ethyl 4-phenyl-2-(phenylamino)thiazole-5-carboxylate
Homo sapiens
Q02172
at pH 8.0 and 22°C
0.05
N-(2,4-dichlorophenyl)naphthalene-2-carboxamide
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.2
N-(3,5-dichlorophenyl)-2-methyl-3-nitrobenzamide
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.00068
N-(3-chlorophenyl)-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.0005
N-(3-fluorophenyl)-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.0007
N-(anthracen-2-yl)-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.01
N-propyl-5-(1H-pyrazol-1-yl)thiophene-2-carboxamide
Homo sapiens
-
above, pH not specified in the publication, temperature not specified in the publication
0.00021
N-[3-fluoro-4-(trifluoromethyl)phenyl]-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.00801
2-(4-(pyridazin-3-yl)phenyl)quinoline-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
0.2
2-(4-(pyridazin-3-yl)phenyl)quinoline-4-carboxylic acid
Homo sapiens
pH 8.0, 22°C
-
additional information
[2-fluoro-2',5'-dimethyl-4'-[6-(3-methyl-2-butenyloxy)pyridin-3-yl]biphenyl-4-yl]-(3-methyl-2-butenyl)amine
Homo sapiens
-
IC50 value 23 ng per ml
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
99
with L-dihydroorotate and 2,6-dichloroindophenol as substrates, at 30°C
150
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
8 - 8.1
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
colon cancer has a high expression of DHODH and HCT-116 is sensitive to DHODH inhibition, while DHODH is not overexpressed in pancreatic cancer
-
DHODH protein is expressed in premalignant and malignant prostate epithelial cells
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
cardiolipin enhances the interaction of truncated DHODH with lipid bilayers, but the presence of the transmembrane domain in human DHODH is necessary for stable binding to and securing its location at the outer surface of the inner mitochondrial membrane
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
physiological function
-
dihydroorotate dehydrogenase is associated with mitochondrial electron transport and required for de novo pyrimidine synthesis, and is required for N-(4-hydroxyphenyl)retinamide-induced reactive oxygen species production and apoptosis. Chemical inhibition of DHODH activity or the reduction of DHODH protein suppresses 4HPR-induced ROS production and apoptosis in transformed skin and prostate epithelial cells, overview
physiological function
-
the enzyme is involved in de novo biosynthesis of pyrimidines
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). PYRD_HUMAN
395
1
42867
Swiss-Prot
Secretory Pathway (Reliability: 5)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
40000
43000
50000
-
x * 40000, recombinant enzyme, SDS-PAGE, x * 50000, native full-length enzyme, SDS-PAGE
40000
-
x * 40000, recombinant enzyme, SDS-PAGE, x * 50000, native full-length enzyme, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 40000, recombinant enzyme, SDS-PAGE, x * 50000, native full-length enzyme, SDS-PAGE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
comparison of ligand-free forms of Schistosoma mansoni DHODH and human DHODH, which undergo different rearrangements in solution
in complex with inhibitors (2Z)-N-(biphenyl-4-yl)-2-cyano-3-hydroxybut-2-enamide, (2Z)-N-(3-chloro-2'-methoxybiphenyl-4-yl)-2-cyano-3-hydroxybut-2-enamide, (2Z)-2-cyano-N-(2,2'-dichlorobiphenyl-4-yl)-3-hydroxybut-2-enamide, and (2Z)-2-cyano-N-(3'-ethoxybiphenyl-4-yl)-3-hydroxybut-2-enamide
in complex with inhibitors 2-[(2,5-dichlorophenyl)sulfanyl]-5-methyl[1,2,4]triazolo[1,5-a]pyrimidin-7-ol and 2-[(2,5-dichlorophenyl)sulfanyl]-5-ethyl[1,2,4]triazolo[1,5-a]pyrimidin-7-ol. bindung induces a structural change in the N-terminal helix. Comparison with binding to Plasmodium falciparum enzyme
in complex with inhibitors 6-chloro-2-(2'-fluorobiphenyl-4-yl)quinoline-4-carboxylic acid and and without any bound inhibitor, to 2.3 A, 2.1 A, and 3.0 A resolution, respectively. Inhibitor 5-methoxy-2-[(4-phenoxyphenyl)amino]benzoic acid 5-methoxy-2-[(4-phenoxyphenyl)amino]benzoic acid interacts with residue Y356. Loop region of residues L68-R72 may interfere with inhibitor/cofactor binding. Loop region N212-L224 may be important for the enzymatic reaction
in complex with low molecular weight compounds that inhibit the enzyme in the nanomolar range, by hanging-drop vapor diffusion method, to 2.15 A resolution
purified recombinant enzyme in complex with inhibitors 41 and 43, X-ray diffraction structure determination and analysis
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
S215C
increase of the average donor-acceptor distances for proton and hydride transfer and disruption of the hydrogen bonding pathways observed for the wild-type enzyme, significant decrease in enzyme activity
H129A
-
complete loss of enzymatic activity, conserved between the human and rat enzyme, required for enzymatic activity
H26A
-
minimal effect on the relative enzyme activity, insensitive against brequinar sodium inhibition, suggested location within the brequinar sodium binding pocket, important role in brequinar sodium binding to enzyme
H364A
-
complete loss of enzymatic activity, conserved between the human and rat enzyme, required for enzymatic activity
H71A
-
complete loss of enzymatic activity, surprising because no conserved residue in the closely related rat enzyme
H71N
-
comparable activity to wild-type, taken together with the results for H71A mutant, the histidine residue is not required at this position, but this site is less permissive than most of the other histidine locations within the enzyme
additional information
additional information
-
N-terminally truncated protein lacking first 29 amino acids
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant protein using immobilized Ni2+ affinity chromatography, full-length protein is solubilized by dodecyl D-maltoside
ammonium sulfate precipitation, affinity chromatography, ion-exchange chromatography
-
ion-exchange, hydroxyapatite, gel filtration for U937, cation-exchange for spleen
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli DH5alpha TAP330, lacking the endogenous gene for the bacterial dihydroorotate dehydrogenase, pyrimidine auxotroph
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
solubilization of full-length enzyme using by dodecyl D-maltoside in order to obtain planar lipid bilayers that are detergent-free. The presence of tetraoleyl cardiolipin in the bilayers significantly enhances the binding between the bilayer and truncated human DHODH. Addition of coenzyme Q10 does not have a detectable effect when compared to bilayers consisting only of 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
synthesis
expression of full-length and N-terminally trucated enzyme lacking 29 amino acids in an Escherichia coli system
medicine
pharmacology
-
A77 1726 inhibits cell growth in multiple myeloma cell lines at clinically achievable concentrations by induction of apoptosis. Inhibition of cell growth is partly due to inhibition of multiple myeloma cell proliferation. A77 1726 shows synergistic and additive activity together with genotoxic agents melphalan, treosulfan, and doxorubicin
additional information
medicine
-
enzyme inhibition is a mechanism of action that may be relevant for the therapeutic effects of leflunomide
medicine
-
great interest in inhibitors as potential therapeutic agents for the treatment of diseases involving aberrant cell proliferation
medicine
-
molecular target of the antiproliferative, immunosuppressive compound brequinar sodium
medicine
-
promising new target for chemotherapeutic intervention in prevention of malaria, synthesized inhibitors show considerable lower affinity for the human DHODH enzyme relative to the Plasmodium DHODH enzyme
additional information
three types of hydrogen bonding pathways, hydrogen bonding of the active base serine to a water molecule, which is hydrogen bonded to the substrate carboxylate group or a threonine residue, the threonine residue is positioned to enable proton transfer to another water molecule leading to the bulk solvent
additional information
-
three types of hydrogen bonding pathways, hydrogen bonding of the active base serine to a water molecule, which is hydrogen bonded to the substrate carboxylate group or a threonine residue, the threonine residue is positioned to enable proton transfer to another water molecule leading to the bulk solvent
additional information
-
kinetic isotope effects on flavin reduction in anaerobic stopped-flow experiments, pKa near 9.4 controlling reduction, similar to that previously reported for the Escherichia coli enzyme
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Liu, S.; Neidhardt, E.A.; Grossman, T.H.; Ocain, T.; Clardy, J.
Structures of human dihydroorotate dehydrogenase in complex with antiproliferative agents
Structure
8
25-33
2000
Homo sapiens
Davis, J.P.; Copeland, R.A.
Histidine to alanine mutants of human dihydroorotate dehydrogenase. Identification of a brequinar-resistant mutant enzyme
Biochem. Pharmacol.
54
459-465
1997
Homo sapiens
Copeland, R.A.; Davis, J.P.; Dowling, R.L.; Lombardo, D.; Murphy, K.B.; Patterson, T.A.
Recombinant human dihydroorotate dehydrogenase: expression, purification, and characterization of a catalytically functional truncated enzyme
Arch. Biochem. Biophys.
323
79-86
1995
Homo sapiens
Bruneau, J.M.; Yea, C.M.; Spinella-Jaegle, S.; Fudali, C.; Woodward, K.; Robson, P.A.; Sautes, C.; Westwood, R.; Kuo, E.A.; Williamson, R.A.; Ruuth, E.
Purification of human dihydro-orotate dehydrogenase and its inhibition by A77 1726, the active metabolite of leflunomide
Biochem. J.
336
299-303
1998
Homo sapiens
-
Ullrich, A.; Knecht, W.; Fries, M.; Loffler, M.
Recombinant expression of N-terminal truncated mutants of the membrane bound mouse, rat and human flavoenzyme dihydroorotate dehydrogenase. A versatile tool to rate inhibitor effects?
Eur. J. Biochem.
268
1861-1868
2001
Homo sapiens, Mus musculus, Rattus norvegicus
Loeffler, M.; Becker, C.; Wegerle, E.; Schuster, G.
Catalytic enzyme histochemistry and biochemical analysis of dihydroorotate dehydrogenase/oxidase and succinate dehydrogenase in mammalian tissues, cells and mitochondria
Histochem. Cell Biol.
105
119-128
1996
Bos taurus, Cavia porcellus, Homo sapiens, Mus musculus, Rattus norvegicus (Q63707), Sus scrofa
Bader, B.; Knecht, W.; Fries, M.; Loffler, M.
Expression, purification, and characterization of histidine-tagged rat and human flavoenzyme dihydroorotate dehydrogenase
Protein Expr. Purif.
13
414-422
1998
Homo sapiens, Rattus norvegicus
Knecht, W.; Bergjohann, U.; Gonski, S.; Kirschbaum, B.; Loffler, M.
Functional expression of a fragment of human dihydroorotate dehydrogenase by means of the baculovirus expression vector system, and kinetic investigation of the purified recombinant enzyme
Eur. J. Biochem.
240
292-301
1996
Homo sapiens
Davis, J.P.; Cain, G.A.; Pitts, W.J.; Magolda, R.L.; Copeland, R.A.
The immunosuppressive metabolite of leflunomide is a potent inhibitor of human dihydroorotate dehydrogenase
Biochemistry
35
1270-1273
1996
Homo sapiens
Knecht, W.; Henseling, J.; Loffler, M.
Kinetics of inhibition of human and rat dihydroorotate dehydrogenase by atovaquone, lawsone derivatives, brequinar sodium and polyporic acid
Chem. Biol. Interact.
124
61-76
2000
Homo sapiens, Rattus norvegicus
McLean, J.E.; Neidhardt, E.A.; Grossman, T.H.; Hedstrom, L.
Multiple inhibitor analysis of the brequinar and leflunomide binding sites on human dihydroorotate dehydrogenase
Biochemistry
40
2194-2200
2001
Homo sapiens
Leban, J.; Saeb, W.; Garcia, G.; Baumgartner, R.; Kramer, B.
Discovery of a novel series of DHODH inhibitors by a docking procedure and QSAR refinement
Bioorg. Med. Chem. Lett.
14
55-58
2004
Homo sapiens
Baldwin, J.; Farajallah, A.M.; Malmquist, N.A.; Rathod, P.K.; Phillips, M.A.
Malarial dihydroorotate dehydrogenase. Substrate and inhibitor specificity
J. Biol. Chem.
277
41827-41834
2002
Homo sapiens, Plasmodium falciparum (Q08210), Plasmodium falciparum
Fagan, R.L.; Nelson, M.N.; Pagano, P.M.; Palfey, B.A.
Mechanism of flavin reduction in class 2 dihydroorotate dehydrogenases
Biochemistry
45
14926-14932
2006
Escherichia coli, Homo sapiens
Baumgartner, R.; Walloschek, M.; Kralik, M.; Gotschlich, A.; Tasler, S.; Mies, J.; Leban, J.
Dual binding mode of a novel series of DHODH inhibitors
J. Med. Chem.
49
1239-1247
2006
Homo sapiens (Q02127), Homo sapiens
Heikkil, T.; Ramsey, C.; Davies, M.; Galtier, C.; Stead, A.M.W.; Johnson, A.P.; Fishwick, C.W.G.; Boa, A.N.; McConkey, G.A.
Design and synthesis of potent inhibitors of the malaria parasite dihydroorotate dehydrogenase
J. Med. Chem.
50
186-191
2007
Homo sapiens, Plasmodium falciparum (Q08210), Plasmodium falciparum
Small, Y.A.; Guallar, V.; Soudackov, A.V.; Hammes-Schiffer, S.
Hydrogen bonding pathways in human dihydroorotate dehydrogenase
J. Phys. Chem. B
110
19704-19710
2006
Homo sapiens (Q02127), Homo sapiens
Zameitat, E.; Freymark, G.; Dietz, C.D.; Loeffler, M.; Boelker, M.
Functional expression of human dihydroorotate dehydrogenase (DHODH) in pyr4 mutants of Ustilago maydis allows target validation of DHODH inhibitors in vivo
Appl. Environ. Microbiol.
73
3371-3379
2007
Homo sapiens (Q02127), Homo sapiens
Walse, B.; Dufe, V.; Svensson, B.; Fritzson, I.; Dahlberg, L.; Khairoullina, A.; Wellmar, U.; Al-Karadaghi, S.
The structures of human dihydroorotate dehydrogenase with and without inhibitor reveal conformational flexibility in the inhibitor and substrate binding sites
Biochemistry
47
8929-8936
2008
Homo sapiens (Q02127), Homo sapiens
Deguchi, M.; Kishino, J.; Hattori, M.; Furue, Y.; Yamamoto, M.; Mochizuki, I.; Iguchi, M.; Hirano, Y.; Hojou, K.; Nagira, M.; Nishitani, Y.; Okazaki, K.; Yasui, K.; Arimura, A.
Suppression of immunoglobulin production by a novel dihydroorotate dehydrogenase inhibitor, S-2678
Eur. J. Pharmacol.
601
163-170
2008
Homo sapiens, Mus musculus
Davies, M.; Heikkila, T.; McConkey, G.; Fishwick, C.; Parsons, M.; Johnson, A.
Structure-based design, synthesis, and characterization of inhibitors of human and Plasmodium falciparum dihydroorotate dehydrogenases
J. Med. Chem.
52
2683-2693
2009
Homo sapiens (Q02127), Homo sapiens, Plasmodium falciparum (Q08210), Plasmodium falciparum
Baumann, P.; Mandl-Weber, S.; Völkl, A.; Adam, C.; Bumeder, I.; Oduncu, F.; Schmidmaier, R.
Dihydroorotate dehydrogenase inhibitor A771726 (leflunomide) induces apoptosis and diminishes proliferation of multiple myeloma cells
Mol. Cancer Ther.
8
366-375
2009
Homo sapiens
Hail, N.; Chen, P.; Kepa, J.J.; Bushman, L.R.; Shearn, C.
Dihydroorotate dehydrogenase is required for N-(4-hydroxyphenyl)retinamide-induced reactive oxygen species production and apoptosis
Free Radic. Biol. Med.
49
109-116
2010
Homo sapiens
Phillips, M.A.; Rathod, P.K.
Plasmodium dihydroorotate dehydrogenase: a promising target for novel anti-malarial chemotherapy
Infect. Disord. Drug Targets
10
226-239
2010
Homo sapiens, Plasmodium falciparum (Q08210), Plasmodium falciparum
Bedingfield, P.T.; Cowen, D.; Acklam, P.; Cunningham, F.; Parsons, M.R.; McConkey, G.A.; Fishwick, C.W.; Johnson, A.P.
Factors influencing the specificity of inhibitor binding to the human and malaria parasite dihydroorotate dehydrogenases
J. Med. Chem.
55
5841-5850
2012
Plasmodium falciparum, Homo sapiens (Q02127), Homo sapiens
Zhu, J.; Han, L.; Diao, Y.; Ren, X.; Xu, M.; Xu, L.; Li, S.; Li, Q.; Dong, D.; Huang, J.; Liu, X.; Zhao, Z.; Wang, R.; Zhu, L.; Xu, Y.; Qian, X.; Li, H.
Design, synthesis, X-ray crystallographic analysis, and biological evaluation of thiazole derivatives as potent and selective inhibitors of human dihydroorotate dehydrogenase
J. Med. Chem.
58
1123-1139
2015
Homo sapiens (Q02172), Homo sapiens
Munier-Lehmann, H.; Lucas-Hourani, M.; Guillou, S.; Helynck, O.; Zanghi, G.; Noel, A.; Tangy, F.; Vidalain, P.O.; Janin, Y.L.
Original 2-(3-alkoxy-1H-pyrazol-1-yl)pyrimidine derivatives as inhibitors of human dihydroorotate dehydrogenase (DHODH)
J. Med. Chem.
58
860-877
2015
Homo sapiens (Q02172), Homo sapiens
Nonato, M.C.; de Padua, R.A.P.; David, J.S.; Reis, R.A.G.; Tomaleri, G.P.; DMuniz Pereira, H.; Calil, F.A.
Structural basis for the design of selective inhibitors for Schistosoma mansoni dihydroorotate dehydrogenase
Biochimie
158
180-190
2019
Schistosoma mansoni (G4VFD7), Schistosoma mansoni, Homo sapiens (Q02127), Homo sapiens
Petrovic, M.; Roschger, C.; Chaudary, S.; Zierer, A.; Mladenovic, M.; Jakovljevic, K.; Markovic, V.; Botta, B.; Joksovic, M.
Potent human dihydroorotate dehydrogenase inhibitory activity of new quinoline-4-carboxylic acids derived from phenolic aldehydes synthesis, cytotoxicity, lipophilicity and molecular docking studies
Bioorg. Chem.
105
104373
2020
Homo sapiens (Q02127), Homo sapiens
Calil, F.A.; David, J.S.; Chiappetta, E.R.C.; Fumagalli, F.; Mello, R.B.; Leite, F.H.A.; Castilho, M.S.; Emery, F.S.; Nonato, M.C.
Ligand-based design, synthesis and biochemical evaluation of potent and selective inhibitors of Schistosoma mansoni dihydroorotate dehydrogenase
Eur. J. Med. Chem.
167
357-366
2019
Schistosoma mansoni (G4VFD7), Schistosoma mansoni, Homo sapiens (Q02127), Homo sapiens
Madak, J.; Cuthbertson, C.; Miyata, Y.; Tamura, S.; Petrunak, E.; Stuckey, J.; Han, Y.; He, M.; Sun, D.; Showalter, H.; Neamati, N.
Design, synthesis, and biological evaluation of 4-quinoline carboxylic acids as inhibitors of dihydroorotate dehydrogenase
J. Med. Chem.
61
5162-5186
2018
Homo sapiens (Q02127)
EXTERNAL LINKS (specific for EC-Number 1.3.5.2)
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
