Crystallization (Comment) | Organism |
---|---|
purified recombinant enzyme in complex with inhibitors 41 and 43, X-ray diffraction structure determination and analysis | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
2-(2'-fluoro-[1,1'-biphenyl]-4-yl)-3-methyl-6-(trifluoromethyl)-1,7-naphthyridine-4-carboxylic acid | - |
Homo sapiens | |
2-(2'-methoxy-[1,1'-biphenyl]-4-yl)quinoline-4-carboxylic acid | - |
Homo sapiens | |
2-(4-(1H-imidazol-1-yl)phenyl)quinoline-4-carboxylic acid | - |
Homo sapiens | |
2-(4-(2-(trifluoromethyl)pyridin-3-yl)phenyl)quinoline-4-carboxylic acid | - |
Homo sapiens | |
2-(4-(2-chloro-6-methylpyridin-3-yl)phenyl)-3-methyl-1,7-naphthyridine-4-carboxylic acid | - |
Homo sapiens | |
2-(4-(2-chloro-6-methylpyridin-3-yl)phenyl)-3-methylquinoline-4-carboxylic acid | - |
Homo sapiens | |
2-(4-(2-chloro-6-methylpyridin-3-yl)phenyl)-6-fluoro-3-methylquinoline-4-carboxylic acid | - |
Homo sapiens | |
2-(4-(2-chloro-6-methylpyridin-3-yl)phenyl)quinoline-4-carboxylic acid | - |
Homo sapiens | |
2-(4-(2-chloropyridin-3-yl)phenyl)-3,6-dimethylquinoline-4-carboxylic acid | - |
Homo sapiens | |
2-(4-(2-chloropyridin-3-yl)phenyl)-3-methyl-1,7-naphthyridine-4-carboxylic acid | - |
Homo sapiens | |
2-(4-(2-chloropyridin-3-yl)phenyl)-3-methyl-6-(trifluoromethyl)-1,7-naphthyridine-4-carboxylic acid | - |
Homo sapiens | |
2-(4-(2-chloropyridin-3-yl)phenyl)-3-methylquinoline-4-carboxylic acid | - |
Homo sapiens | |
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 | Homo sapiens | |
2-(4-(2-chloropyridin-3-yl)phenyl)quinoline-4-carboxylic acid | - |
Homo sapiens | |
2-(4-(2-fluoro-6-methylpyridin-3-yl)phenyl)-3-methylquinoline-4-carboxylic acid | - |
Homo sapiens | |
2-(4-(2-fluoropyridin-3-yl)phenyl)-3-methylquinoline-4-carboxylic acid | - |
Homo sapiens | |
2-(4-(2-fluoropyridin-3-yl)phenyl)quinoline-4-carboxylic acid | - |
Homo sapiens | |
2-(4-(2-methoxypyridin-3-yl)phenyl)quinoline-4-carboxylic acid | - |
Homo sapiens | |
2-(4-(2-methylpyridin-3-yl)phenyl)quinoline-4-carboxylic acid | - |
Homo sapiens | |
2-(4-(4-(trifluoromethyl)pyridin-3-yl)phenyl)quinoline-4-carboxylic acid | - |
Homo sapiens | |
2-(4-(4-methylpyridin-3-yl)phenyl)quinoline-4-carboxylic acid | - |
Homo sapiens | |
2-(4-(6-fluoropyridin-3-yl)phenyl)quinoline-4-carboxylic acid | - |
Homo sapiens | |
2-(4-(piperidin-1-yl)phenyl)quinoline-4-carboxylic acid | - |
Homo sapiens | |
2-(4-(pyridazin-3-yl)phenyl)quinoline-4-carboxylic acid | - |
Homo sapiens | |
2-(4-(pyridin-2-yl)phenyl)quinoline-4-carboxylic acid | - |
Homo sapiens | |
2-(4-(pyridin-3-yl)phenyl)quinoline-4-carboxylic acid | - |
Homo sapiens | |
2-(4-(pyridin-4-yl)phenyl)quinoline-4-carboxylic acid | - |
Homo sapiens | |
2-(4-(pyrimidin-2-yl)phenyl)quinoline-4-carboxylic acid | - |
Homo sapiens | |
2-(4-cyclohexylphenyl)quinoline-4-carboxylic acid | - |
Homo sapiens | |
2-(4-isobutylphenyl)quinoline-4-carboxylic acid | - |
Homo sapiens | |
2-(4-isopropylphenyl)quinoline-4-carboxylic acid | - |
Homo sapiens | |
2-(4-methylphenyl)quinoline-4-carboxylic acid | - |
Homo sapiens | |
2-(4-morpholinophenyl)quinoline-4-carboxylic acid | - |
Homo sapiens | |
2-([1,1'-biphenyl]-4-yl)-3-methyl-1,6-naphthyridine-4-carboxylic acid | - |
Homo sapiens | |
2-([1,1'-biphenyl]-4-yl)-3-methyl-1,7-naphthyridine-4-carboxylic acid | - |
Homo sapiens | |
2-([1,1'-biphenyl]-4-yl)-3-methyl-1,8-naphthyridine-4-carboxylic acid | - |
Homo sapiens | |
2-([1,1'-biphenyl]-4-yl)-3-methyl-6-(trifluoromethyl)-1,7-naphthyridine-4-carboxylic acid | - |
Homo sapiens | |
2-([1,1'-biphenyl]-4-yl)-3-methylquinoline-4-carboxylic acid | - |
Homo sapiens | |
2-([1,1'-biphenyl]-4-yl)quinoline-4-carboxylic acid | - |
Homo sapiens | |
5-methyl-N-[4-(trifluoromethyl)phenyl]-1,2-oxazole-4-carboxamide | - |
Homo sapiens | |
6-chloro-2-(4-(2-chloro-6-methylpyridin-3-yl)phenyl)-3-methylquinoline-4-carboxylic acid | - |
Homo sapiens | |
6-chloro-2-(4-(2-chloropyridin-3-yl)phenyl)-3-methylquinoline-4-carboxylic acid | - |
Homo sapiens | |
6-chloro-2-(4-(2-fluoropyridin-3-yl)phenyl)-3-methylquinoline-4-carboxylic acid | - |
Homo sapiens | |
6-fluoro-2-(2'-fluoro[1,1'-biphenyl]-4-yl)-3-methylquinoline-4-carboxylic acid | - |
Homo sapiens | |
6-fluoro-2-(4-(2-fluoro-6-methylpyridin-3-yl)phenyl)-3-methylquinoline-4-carboxylic acid | - |
Homo sapiens | |
6-fluoro-2-(4-(2-fluoropyridin-3-yl)phenyl)-3-methylquinoline-4-carboxylic acid | - |
Homo sapiens | |
brequinar | - |
Homo sapiens | |
leflunomide | - |
Homo sapiens | |
methyl 2-(4-(4-(trifluoromethyl)pyridin-3-yl)phenyl)quinoline-4-carboxylate | - |
Homo sapiens | |
methyl 2-(4-(piperidin-1-yl)phenyl)quinoline-4-carboxylate | - |
Homo sapiens | |
methyl 2-(4-(pyridin-3-yl)phenyl)quinoline-4-carboxylate | - |
Homo sapiens | |
methyl 2-(4-cyclohexylphenyl)quinoline-4-carboxylate | - |
Homo sapiens | |
methyl 2-([1,1'-biphenyl]-4-yl)quinoline-4-carboxylate | - |
Homo sapiens | |
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 | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
(S)-dihydroorotate + ubiquinone | Homo sapiens | - |
orotate + ubiquinol | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | Q02127 | - |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
carcinoma cell | colon cancer has a high expression of DHODH and HCT-116 is sensitive to DHODH inhibition, while DHODH is not overexpressed in pancreatic cancer | Homo sapiens | - |
colonic cancer cell | - |
Homo sapiens | - |
HCT-116 cell | - |
Homo sapiens | - |
MiaPaCa-2 cell | - |
Homo sapiens | - |
pancreatic cancer cell | - |
Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
(S)-dihydroorotate + ubiquinone | - |
Homo sapiens | orotate + ubiquinol | - |
? |
Synonyms | Comment | Organism |
---|---|---|
DHODH | - |
Homo sapiens |
dihydroorotate dehydrogenase | - |
Homo sapiens |
hDHODH | - |
Homo sapiens |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
22 | - |
assay at room temperature | Homo sapiens |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
8 | - |
assay at | Homo sapiens |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.00000971 | - |
pH 8.0, 22°C | Homo sapiens | 2-(4-(2-chloropyridin-3-yl)phenyl)-6-fluoro-3-methylquinoline-4-carboxylic acid | |
0.0000118 | - |
pH 8.0, 22°C | Homo sapiens | 2-(2'-fluoro-[1,1'-biphenyl]-4-yl)-3-methyl-6-(trifluoromethyl)-1,7-naphthyridine-4-carboxylic acid | |
0.0000212 | - |
pH 8.0, 22°C | Homo sapiens | 2-([1,1'-biphenyl]-4-yl)-3-methyl-6-(trifluoromethyl)-1,7-naphthyridine-4-carboxylic acid | |
0.0000221 | - |
pH 8.0, 22°C | Homo sapiens | 2-(4-(2-methylpyridin-3-yl)phenyl)quinoline-4-carboxylic acid | |
0.0000262 | - |
pH 8.0, 22°C | Homo sapiens | 2-(4-(2-chloro-6-methylpyridin-3-yl)phenyl)-6-fluoro-3-methylquinoline-4-carboxylic acid | |
0.0000283 | - |
pH 8.0, 22°C | Homo sapiens | 2-([1,1'-biphenyl]-4-yl)-3-methyl-1,7-naphthyridine-4-carboxylic acid | |
0.0000327 | - |
pH 8.0, 22°C | Homo sapiens | 2-(4-(2-chloropyridin-3-yl)phenyl)quinoline-4-carboxylic acid | |
0.000036 | - |
pH 8.0, 22°C | Homo sapiens | 6-chloro-2-(4-(2-chloropyridin-3-yl)phenyl)-3-methylquinoline-4-carboxylic acid | |
0.000051 | - |
pH 8.0, 22°C | Homo sapiens | 2-([1,1'-biphenyl]-4-yl)quinoline-4-carboxylic acid | |
0.0000542 | - |
pH 8.0, 22°C | Homo sapiens | 2-(4-(2-chloropyridin-3-yl)phenyl)-3,6-dimethylquinoline-4-carboxylic acid | |
0.0000543 | - |
pH 8.0, 22°C | Homo sapiens | 2-(4-(2-chloropyridin-3-yl)phenyl)-3-methylquinoline-4-carboxylic acid | |
0.0000744 | - |
pH 8.0, 22°C | Homo sapiens | 6-chloro-2-(4-(2-chloro-6-methylpyridin-3-yl)phenyl)-3-methylquinoline-4-carboxylic acid | |
0.0000754 | - |
pH 8.0, 22°C | Homo sapiens | 2-([1,1'-biphenyl]-4-yl)-3-methylquinoline-4-carboxylic acid | |
0.0000794 | - |
pH 8.0, 22°C | Homo sapiens | 6-fluoro-2-(4-(2-fluoropyridin-3-yl)phenyl)-3-methylquinoline-4-carboxylic acid | |
0.000127 | - |
pH 8.0, 22°C | Homo sapiens | 2-(2'-methoxy-[1,1'-biphenyl]-4-yl)quinoline-4-carboxylic acid | |
0.000148 | - |
pH 8.0, 22°C | Homo sapiens | 2-(4-(2-(trifluoromethyl)pyridin-3-yl)phenyl)quinoline-4-carboxylic acid | |
0.000165 | - |
pH 8.0, 22°C | Homo sapiens | 2-(4-(2-methoxypyridin-3-yl)phenyl)quinoline-4-carboxylic acid | |
0.000165 | - |
pH 8.0, 22°C | Homo sapiens | 6-chloro-2-(4-(2-fluoropyridin-3-yl)phenyl)-3-methylquinoline-4-carboxylic acid | |
0.000184 | - |
pH 8.0, 22°C | Homo sapiens | 2-(4-(2-chloro-6-methylpyridin-3-yl)phenyl)-3-methylquinoline-4-carboxylic acid | |
0.000201 | - |
pH 8.0, 22°C | Homo sapiens | 2-(4-(2-chloropyridin-3-yl)phenyl)-3-methyl-6-(trifluoromethyl)-1,7-naphthyridine-4-carboxylic acid | |
0.000235 | - |
pH 8.0, 22°C | Homo sapiens | 2-(4-(2-chloro-6-methylpyridin-3-yl)phenyl)quinoline-4-carboxylic acid | |
0.00025 | - |
pH 8.0, 22°C | Homo sapiens | 2-(4-cyclohexylphenyl)quinoline-4-carboxylic acid | |
0.000259 | - |
pH 8.0, 22°C | Homo sapiens | 2-(4-(2-chloropyridin-3-yl)phenyl)-3-methyl-1,7-naphthyridine-4-carboxylic acid | |
0.000373 | - |
pH 8.0, 22°C | Homo sapiens | 2-(4-(4-methylpyridin-3-yl)phenyl)quinoline-4-carboxylic acid | |
0.000391 | - |
pH 8.0, 22°C | Homo sapiens | 2-(4-(pyridin-3-yl)phenyl)quinoline-4-carboxylic acid | |
0.000504 | - |
pH 8.0, 22°C | Homo sapiens | 2-(4-(2-fluoropyridin-3-yl)phenyl)-3-methylquinoline-4-carboxylic acid | |
0.00073 | - |
pH 8.0, 22°C | Homo sapiens | brequinar | |
0.00104 | - |
pH 8.0, 22°C | Homo sapiens | 2-(4-isobutylphenyl)quinoline-4-carboxylic acid | |
0.00122 | - |
pH 8.0, 22°C | Homo sapiens | 2-([1,1'-biphenyl]-4-yl)-3-methyl-1,8-naphthyridine-4-carboxylic acid | |
0.00142 | - |
pH 8.0, 22°C | Homo sapiens | 2-(4-(2-fluoropyridin-3-yl)phenyl)quinoline-4-carboxylic acid | |
0.00143 | - |
pH 8.0, 22°C | Homo sapiens | 2-(4-(4-(trifluoromethyl)pyridin-3-yl)phenyl)quinoline-4-carboxylic acid | |
0.00248 | - |
pH 8.0, 22°C | Homo sapiens | 2-(4-(2-fluoro-6-methylpyridin-3-yl)phenyl)-3-methylquinoline-4-carboxylic acid | |
0.00279 | - |
pH 8.0, 22°C | Homo sapiens | 2-([1,1'-biphenyl]-4-yl)-3-methyl-1,6-naphthyridine-4-carboxylic acid | |
0.00331 | - |
pH 8.0, 22°C | Homo sapiens | 6-fluoro-2-(4-(2-fluoro-6-methylpyridin-3-yl)phenyl)-3-methylquinoline-4-carboxylic acid | |
0.00341 | - |
pH 8.0, 22°C | Homo sapiens | 2-(4-isopropylphenyl)quinoline-4-carboxylic acid | |
0.00526 | - |
pH 8.0, 22°C | Homo sapiens | 2-(4-(2-chloro-6-methylpyridin-3-yl)phenyl)-3-methyl-1,7-naphthyridine-4-carboxylic acid | |
0.00755 | - |
pH 8.0, 22°C | Homo sapiens | 2-(4-(pyridin-4-yl)phenyl)quinoline-4-carboxylic acid | |
0.00801 | - |
pH 8.0, 22°C | Homo sapiens | 2-(4-(pyridazin-3-yl)phenyl)quinoline-4-carboxylic acid | |
0.00807 | - |
pH 8.0, 22°C | Homo sapiens | 2-(4-(piperidin-1-yl)phenyl)quinoline-4-carboxylic acid | |
0.0084 | - |
pH 8.0, 22°C | Homo sapiens | 2-(4-(1H-imidazol-1-yl)phenyl)quinoline-4-carboxylic acid | |
0.0101 | - |
pH 8.0, 22°C | Homo sapiens | 2-(4-(pyridin-2-yl)phenyl)quinoline-4-carboxylic acid | |
0.0125 | - |
pH 8.0, 22°C | Homo sapiens | 2-(4-(6-fluoropyridin-3-yl)phenyl)quinoline-4-carboxylic acid | |
0.05 | - |
pH 8.0, 22°C | Homo sapiens | methyl 2-(4-(4-(trifluoromethyl)pyridin-3-yl)phenyl)quinoline-4-carboxylate | |
0.144 | - |
pH 8.0, 22°C | Homo sapiens | 2-(4-methylphenyl)quinoline-4-carboxylic acid | |
0.2 | - |
pH 8.0, 22°C | Homo sapiens | 2-(4-(pyridazin-3-yl)phenyl)quinoline-4-carboxylic acid | |
0.2 | - |
pH 8.0, 22°C | Homo sapiens | 2-(4-(pyrimidin-2-yl)phenyl)quinoline-4-carboxylic acid | |
0.2 | - |
pH 8.0, 22°C | Homo sapiens | 2-(4-morpholinophenyl)quinoline-4-carboxylic acid | |
0.2 | - |
pH 8.0, 22°C | Homo sapiens | methyl 2-(4-(piperidin-1-yl)phenyl)quinoline-4-carboxylate | |
0.2 | - |
pH 8.0, 22°C | Homo sapiens | methyl 2-(4-(pyridin-3-yl)phenyl)quinoline-4-carboxylate | |
0.2 | - |
pH 8.0, 22°C | Homo sapiens | methyl 2-(4-cyclohexylphenyl)quinoline-4-carboxylate | |
0.2 | - |
pH 8.0, 22°C | Homo sapiens | methyl 2-([1,1'-biphenyl]-4-yl)quinoline-4-carboxylate |