Literature summary for 1.3.5.2 extracted from

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 (2018), J. Med. Chem., 61, 5162-5186 .

Crystallization (Commentary)

Crystallization (Comment)	Organism
purified recombinant enzyme in complex with inhibitors 41 and 43, X-ray diffraction structure determination and analysis	Homo sapiens

Inhibitors

Inhibitors	Comment	Organism
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/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
(S)-dihydroorotate + ubiquinone	Homo sapiens	-	orotate + ubiquinol	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	Q02127	-	-

Source Tissue

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 and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
(S)-dihydroorotate + ubiquinone	-	Homo sapiens	orotate + ubiquinol	-	?

Synonyms

Synonyms	Comment	Organism
DHODH	-	Homo sapiens
dihydroorotate dehydrogenase	-	Homo sapiens
hDHODH	-	Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C]	Temperature Optimum Maximum [°C]	Comment	Organism
22	-	assay at room temperature	Homo sapiens

pH Optimum

pH Optimum Minimum	pH Optimum Maximum	Comment	Organism
8	-	assay at	Homo sapiens

IC50 Value

IC50 Value	IC50 Value Maximum	Comment	Organism	Inhibitor
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