CYP2C8

Summary

CYP2C8 (cytochrome P450 family 2 subfamily C member 8, HGNC:2622) is a protein-coding gene on chromosome 10q23.33, encoding Cytochrome P450 2C8 (P10632). A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins.

This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and its expression is induced by phenobarbital. The enzyme is known to metabolize many xenobiotics, including the anticonvulsive drug mephenytoin, benzo(a)pyrene, 7-ethyoxycoumarin, and the anti-cancer drug taxol. This gene is located within a cluster of cytochrome P450 genes on chromosome 10q24. Several transcript variants encoding a few different isoforms have been found for this gene.

Source: NCBI Gene 1558 — RefSeq curated summary.

At a glance

• GWAS associations: 15
• Clinical variants (ClinVar): 76 total — 1 pathogenic
• Druggable target: yes — 62 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): activating (oncogene-like) across 2 cancer types
• MANE Select transcript: NM_000770

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2622
Approved symbol	CYP2C8
Name	cytochrome P450 family 2 subfamily C member 8
Location	10q23.33
Locus type	gene with protein product
Status	Approved
Aliases	CPC8
Ensembl gene	ENSG00000138115
Ensembl biotype	protein_coding
OMIM	601129
Entrez	1558

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 23 protein_coding, 5 retained_intron, 3 nonsense_mediated_decay

ENST00000371270, ENST00000479946, ENST00000490994, ENST00000525991, ENST00000526814, ENST00000527420, ENST00000527953, ENST00000531714, ENST00000533320, ENST00000535898, ENST00000623108, ENST00000628935, ENST00000854616, ENST00000854617, ENST00000854618, ENST00000854619, ENST00000854620, ENST00000854621, ENST00000854622, ENST00000854623, ENST00000854624, ENST00000854625, ENST00000854626, ENST00000854627, ENST00000854628, ENST00000854629, ENST00000854630, ENST00000854631, ENST00000854632, ENST00000854633, ENST00000854634

RefSeq mRNA: 4 — MANE Select: NM_000770 NM_000770, NM_001198853, NM_001198854, NM_001198855

CCDS: CCDS55721, CCDS73166, CCDS7438

Canonical transcript exons

ENST00000371270 — 9 exons

Exon	Start	End
ENSE00002186511	95069235	95069497
ENSE00003466092	95038897	95039038
ENSE00003583382	95058335	95058511
ENSE00003584515	95064800	95064960
ENSE00003588097	95067208	95067357
ENSE00003593839	95036772	95037309
ENSE00003619515	95045810	95045951
ENSE00003649095	95067529	95067691
ENSE00003677965	95042890	95043077

Expression profiles

Bgee: expression breadth ubiquitous, 185 present calls, max score 99.44.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 3.0025 / max 1100.5583, expressed in 13 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
110734	2.6784	11
110733	0.3241	9

Top tissues by expression

287 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	99.44	gold quality
liver	UBERON:0002107	97.81	gold quality
sperm	CL:0000019	94.30	gold quality
male germ cell	CL:0000015	90.47	gold quality
pancreatic ductal cell	CL:0002079	82.72	silver quality
right uterine tube	UBERON:0001302	81.69	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.54	silver quality
gall bladder	UBERON:0002110	78.85	gold quality
epithelial cell of pancreas	CL:0000083	76.93	silver quality
adenohypophysis	UBERON:0002196	74.71	gold quality
left adrenal gland cortex	UBERON:0035825	74.68	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	74.66	gold quality
body of stomach	UBERON:0001161	74.44	gold quality
right adrenal gland cortex	UBERON:0035827	74.07	gold quality
pituitary gland	UBERON:0000007	73.93	gold quality
right adrenal gland	UBERON:0001233	73.86	gold quality
left adrenal gland	UBERON:0001234	73.21	gold quality
right testis	UBERON:0004534	73.08	gold quality
left testis	UBERON:0004533	72.86	gold quality
body of pancreas	UBERON:0001150	72.73	gold quality
adrenal cortex	UBERON:0001235	72.17	gold quality
bronchial epithelial cell	CL:0002328	72.06	gold quality
right frontal lobe	UBERON:0002810	71.42	gold quality
stomach	UBERON:0000945	70.51	gold quality
Brodmann (1909) area 9	UBERON:0013540	70.23	gold quality
testis	UBERON:0000473	69.93	gold quality
nucleus accumbens	UBERON:0001882	69.58	gold quality
adrenal gland	UBERON:0002369	69.57	gold quality
middle temporal gyrus	UBERON:0002771	69.46	silver quality
pancreas	UBERON:0001264	69.28	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-9	yes	56.57
E-ANND-3	yes	4.37

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, FOXA3, HNF4A, NR1I2, NR1I3, NR3C1, RORA, RORC

miRNA regulators (miRDB)

17 targeting CYP2C8, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-4797-5P	99.39	68.01	1354
HSA-MIR-6871-5P	98.90	66.67	671
HSA-MIR-382-3P	98.83	67.10	1074
HSA-MIR-34B-3P	98.70	67.40	1171
HSA-MIR-634	97.74	67.11	818
HSA-MIR-3665	97.73	65.08	975
HSA-MIR-585-5P	97.54	69.02	955
HSA-MIR-4727-3P	96.75	64.97	415

Literature-anchored findings (GeneRIF, showing 40)

• the frequency of polymorphisms was analyzed and the number of subjects carrying both of the CYP2C8*1*3 and CYP2C9*1*2 was found to be 4.5-fold higher than expected (PMID:12435384)
• a novel peripheral binding site in P450s that may contribute to drug-drug interactions in P450 metabolism (PMID:14676196)
• CYP2C8 single nucleotide polymorphisms could influence the metabolism of CYP2C8 substrates (PMID:15716363)
• there is an association between CYP2J2*7 (but not CYP2C8*3) genotype and hypertension in Caucasian males and Caucasians without a family history of hypertension (PMID:15864120)
• transcriptional regulation is controlled by constitutive androstane receptor, pregnane X receptor, glucocorticoid receptor, and hepatic nuclear factor 4alpha (PMID:15933212)
• CYP2C8*3 alleles were in strong linkage disequilibrium in both the hypertensive and healthy African American group. (PMID:16202848)
• In sigmoid colon, protein levels of CYP2C8 are significantly higher by ~73% than in the descending colon. (PMID:16253141)
• Polymorphism in the CYP2C8 gene in Portugese was studied. (PMID:16475901)
• The findings summarized in this review suggest that among individuals with Asian or European ancestry, intraethnic differences in the risk of developing adverse effects with drugs that are CYP2C8 or CYP2C9 substrates are to be expected. (PMID:16646575)
• comprehensive analysis of the distribution of sEH, CYP2C8, 2C9 and 2J2 in human neoplastic tissues using tissue micro-arrays (PMID:16957870)
• The polymorphism of the CYP2C8 gene among an African population showed the expected distribution/ (PMID:17175891)
• Allelic variants of UGT2B7, CYP2C8, and ABCC2, which may predispose to the formation and accumulation of reactive diclofenac metabolites are associated with diclofenac hepatotoxicity (PMID:17241877)
• Differences exist in protein levels of certain CYPs in non-malignant esophageal tissue (e.g. CYP2C8, CYP3A4, CYP3A5, and CYP2E1) between SCC patients and healthy subjects and may contribute to the development of squamous-cell carcinoma in the esophagus. (PMID:17373732)
• cigarette smoking may modify the relationship between the I264M and K399R polymorphisms in CYP2C8 and coronary heart disease risk in Caucasians (PMID:17429317)
• *IG group haplotypes might be associated with reduced CYP2C8 activity, possibly through its reduced protein levels. (PMID:17558302)
• These results suggest that alterations in CYP2C8 and CYP2C9 at the CYP2C gene locus are associated with the risk for essential tremor. (PMID:17627038)
• The CYP2C8 enzyme is responsible for the reaction leading to O-demethylated silybin. (PMID:17670841)
• Two novel common CYP2C8 haplotypes are identified that significantly associate with altered rate of CYP2C8-dependent drug metabolism in Caucasians in vitro and in vivo. (PMID:17923851)
• genetic variation in CYP2C8 moderately modulates 8,9-, 11,12-, and 14,15-epoxyeicosatrienic acid (EET) formation as reflected in urinary dihydroxyeicosatrienoic acid ezcretion. (PMID:18303964)
• analysis of cytochrome P450 2C8 substrate binding to montelukast, troglitazone, felodipine, and 9-cis-retinoic acid (PMID:18413310)
• no association between variation in CYP2C8 or CYP2C9 and myocardial infarction or stroke (PMID:18496133)
• Relationship between CYP2C8 genotypes and diclofenac 5-hydroxylation in healthy Spanish volunteers is reported. (PMID:18548238)
• The presence of isoleucine at position 264 in CYP2C8 was found to be important for proper haem insertion and protein folding. (PMID:18574320)
• Individuals homozygous for the T allele had an increased likelihood of developing osteonecrosis of the jaw (odds ratio 12.75, 95% confidence interval 3.7-43.5). (PMID:18594024)
• Metabolism of racemic, S-ibuprofen and R-ibuprofen in CYP2C9*3; an increased R-ibuprofen metabolism in CYP2C8*3; and fewer adverse events in CYP2C8*3 volunteers are suggested (PMID:18694831)
• This study examined the association between calcineurin inhibitors-induced nephrotoxicity in liver transplant patients and CYP2C8 and CYP2J2 polymorphisms. (PMID:18769365)
• Polymorphisms in the CYP2C8 drug-metabolising enzyme gene, but not the SLCO1B1 drug transporter gene, significantly influence rosiglitazone disposition in humans. (PMID:19129086)
• CYP2C8 clinical pharmacogenetic data are provided by drug class, followed by a discussion of the future of CYP2C8 clinical pharmacogenetic research–REVIEW (PMID:19761371)
• Studied the recovery of CYP2C8 activity after discontinuation of gemfibrozil treatment using repaglinide as a probe drug, to estimate the in vivo turnover half-life of CYP2C8. (PMID:19773535)
• Frequencies of CYP2C8/9 polymorphisms in breast cancer patients were similar to healthy European populations. (PMID:19935798)
• Allele frequency distributions for CYP2C8 among the Ghanaian population are comparable to other African ethnic groups but significantly differ from Caucasian and Asian populations (PMID:19954515)
• Residue 476 was involved in contact with substrate and was important for maintaining the thermal stability of CYP2C8. (PMID:20013305)
• CYP2C8 haplotype C and CYP3A5*3 are associated with lower risk of paclitaxel-related neurotoxicity (PMID:20212519)
• Review human CYP2C8 structure, substrate specificity, inhibitor selectivity, inducers and polymorphisms. (PMID:20214592)
• Single nucleotide polymorphism rs1058932C>T within the CYP2C8 gene is associated with an increased risk of myocardial infarction, which is, possibly because of a vascular effect of sex steroids, highest in males. (PMID:20436375)
• CYP2C19*17 is a frequent genetic variant in Nordic populations that exists in strong linkage disequilibrium with wildtype CYP2C8*1 and CYP2C9*1 alleles, which makes it a determinant for a haplotype exhibiting an efficient CYP2C substrate metabolism (PMID:20665013)
• CYP2C polymorphism was not associated with patent ductus arteriosus response to ibuprofen (PMID:20808793)
• Two important nonsubstrate recognition site residues of CYP2C8 are closely related to heme binding and/or substrate binding. This discovery could explain clinically individual differences in the metabolism of antineoplastic drugs. (PMID:20848147)
• In this pilot investigation, we found an increased prevalence of the CYP2C8*4 mutation in the Type 2 diabetic patient group. (PMID:20857895)
• discusses linkage disequilibrium between the CYP2C19*17 and CYP2C8*2 alleles in populations of African descent (PMID:20890775)

Cross-species orthologs

0 orthologs

Paralogs (15): CYP2W1 (ENSG00000073067), CYP2D6 (ENSG00000100197), CYP2C18 (ENSG00000108242), CYP2E1 (ENSG00000130649), CYP2J2 (ENSG00000134716), CYP2C9 (ENSG00000138109), CYP2U1 (ENSG00000155016), CYP2C19 (ENSG00000165841), CYP2S1 (ENSG00000167600), CYP2R1 (ENSG00000186104), CYP2B6 (ENSG00000197408), CYP2F1 (ENSG00000197446), CYP2A13 (ENSG00000197838), CYP2A7 (ENSG00000198077), CYP2A6 (ENSG00000255974)

Protein

Protein identifiers

Cytochrome P450 2C8 — P10632 (reviewed: P10632)

Alternative names: CYPIIC8, Cytochrome P450 IIC2, Cytochrome P450 MP-12, Cytochrome P450 MP-20, Cytochrome P450 form 1, S-mephenytoin 4-hydroxylase

All UniProt accessions (6): P10632, A0A0D9SG51, B7Z1F5, E9PIW6, E9PLI9, G3V188

UniProt curated annotations — full annotation on UniProt →

Function. A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH–hemoprotein reductase). Primarily catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) with a preference for the last double bond. Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes all trans-retinoic acid toward its 4-hydroxylated form. Displays 16-alpha hydroxylase activity toward estrogen steroid hormones, 17beta-estradiol (E2) and estrone (E1). Plays a role in the oxidative metabolism of xenobiotics. It is the principal enzyme responsible for the metabolism of the anti-cancer drug paclitaxel (taxol).

Subcellular location. Endoplasmic reticulum membrane. Microsome membrane.

Induction. By phenobarbital.

Pathway. Steroid metabolism. Lipid metabolism; arachidonate metabolism. Cofactor metabolism; retinol metabolism.

Polymorphism. Several alleles are found in the human population, contributing to interindividual variations in the therapeutic efficacy and toxicity of a myriad of drugs such as paclitaxel or amodiaquine. The allele shown here is CYP2C8*1. CYP2C8 genetic variations are associated with altered drug metabolism and adverse drug effects including acute rhabdomyolysis after cerivastatin use [MIM:618018].

Similarity. Belongs to the cytochrome P450 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P10632-1	1	yes
P10632-2	2

RefSeq proteins (4): NP_000761, NP_001185782, NP_001185783, NP_001185784 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001128	Cyt_P450	Family
IPR002401	Cyt_P450_E_grp-I	Family
IPR017972	Cyt_P450_CS	Conserved_site
IPR036396	Cyt_P450_sf	Homologous_superfamily
IPR050182	Cytochrome_P450_fam2	Family

Pfam: PF00067

Enzyme classification (BRENDA):

• EC 1.14.14.1 — unspecific monooxygenase (BRENDA: 53 organisms, 363 substrates, 53 inhibitors, 69 Km, 40 kcat entries)

Substrate kinetics (BRENDA)

24 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
FENTHION	0.0016–0.131	18
NADH	0.004–1.43	13
NADPH	0.002–0.13	6
(1R)-CIS-PERMETHRIN	0.055–0.061	2
(1R)-TRANS-PERMETHRIN	0.115–0.131	2
(1S)-CIS-PERMETHRIN	0.057–0.063	2
(1S)-TRANS-PERMETHRIN	0.101–0.106	2
7-ETHOXYRESORUFIN	0.0001–0.0012	2
MYRISTIC ACID	0.023–0.11	2
OLEIC ACID	0.075–0.084	2
OMEGA-(P-NITROPHENYL)DECANOIC ACID	0.0064–0.0245	2
OMEGA-(P-NITROPHENYL)DODECANOIC ACID	0.0065–0.0104	2
OMEGA-(P-NITROPHENYL)OCTANOIC ACID	0.0319–0.0618	2
12-METHYL-TETRADECANOIC ACID	0.0129	1
13-METHYL-TETRADECANOIC ACID	0.0165	1

Catalyzed reactions (Rhea), 12 shown:

• an organic molecule + reduced [NADPH–hemoprotein reductase] + O2 = an alcohol + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:17149)
• (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + reduced [NADPH–hemoprotein reductase] + O2 = (17R,18S)-epoxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:39779)
• (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + reduced [NADPH–hemoprotein reductase] + O2 = (17S,18R)-epoxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:39783)
• estrone + reduced [NADPH–hemoprotein reductase] + O2 = 16alpha-hydroxyestrone + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:47204)
• 17beta-estradiol + reduced [NADPH–hemoprotein reductase] + O2 = 16alpha,17beta-estriol + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:47332)
• (5Z,8Z,11Z,14Z)-eicosatetraenoate + reduced [NADPH–hemoprotein reductase] + O2 = (14S,15R)-epoxy-(5Z,8Z,11Z)-eicosatrienoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:49856)
• (5Z,8Z,11Z,14Z)-eicosatetraenoate + reduced [NADPH–hemoprotein reductase] + O2 = (14R,15S)-epoxy-(5Z,8Z,11Z)-eicosatrienoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:49860)
• (5Z,8Z,11Z,14Z)-eicosatetraenoate + reduced [NADPH–hemoprotein reductase] + O2 = (11S,12R)-epoxy-(5Z,8Z,14Z)-eicosatrienoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:49876)
• (5Z,8Z,11Z,14Z)-eicosatetraenoate + reduced [NADPH–hemoprotein reductase] + O2 = (11R,12S)-epoxy-(5Z,8Z,14Z)-eicosatrienoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:49880)
• all-trans-retinoate + reduced [NADPH–hemoprotein reductase] + O2 = all-trans-4-hydroxyretinoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:51984)
• (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + reduced [NADPH–hemoprotein reductase] + O2 = (19R,20S)-epoxy-(4Z,7Z,10Z,13Z,16Z)-docosapentaenoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:52120)
• (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + reduced [NADPH–hemoprotein reductase] + O2 = (19S,20R)-epoxy-(4Z,7Z,10Z,13Z,16Z)-docosapentaenoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:52124)

UniProt features (74 total): helix 22, sequence variant 17, strand 13, sequence conflict 8, turn 6, binding site 4, splice variant 2, chain 1, modified residue 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
2NNJ	X-RAY DIFFRACTION	2.28
2NNH	X-RAY DIFFRACTION	2.6
1PQ2	X-RAY DIFFRACTION	2.7
2VN0	X-RAY DIFFRACTION	2.7
2NNI	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P10632-F1	93.07	0.78

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (4): 100; 204; 241; 435 (axial binding residue)

Post-translational modifications (1): 100

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-211981	Xenobiotics
R-HSA-211999	CYP2E1 reactions
R-HSA-2142670	Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET)
R-HSA-2142816	Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE)
R-HSA-9027307	Biosynthesis of maresin-like SPMs
R-HSA-9749641	Aspirin ADME

MSigDB gene sets: 160 (showing top): GOBP_LIPID_MODIFICATION, MODULE_93, REACTOME_BIOLOGICAL_OXIDATIONS, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, GNF2_GSTM1, GNF2_HPN, GOZGIT_ESR1_TARGETS_DN, GOBP_OXIDATIVE_DEMETHYLATION, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_LONG_CHAIN_FATTY_ACID_METABOLIC_PROCESS, SAENZ_DETOX_PATHWAY_AND_CARCINOGENESIS_DN, GOBP_RETINOL_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS

GO Biological Process (17): lipid hydroxylation (GO:0002933), obsolete organic acid metabolic process (GO:0006082), xenobiotic metabolic process (GO:0006805), steroid metabolic process (GO:0008202), estrogen metabolic process (GO:0008210), epoxygenase P450 pathway (GO:0019373), xenobiotic catabolic process (GO:0042178), retinol metabolic process (GO:0042572), retinoic acid metabolic process (GO:0042573), long-chain fatty acid biosynthetic process (GO:0042759), icosanoid biosynthetic process (GO:0046456), oxidative demethylation (GO:0070989), omega-hydroxylase P450 pathway (GO:0097267), lipid metabolic process (GO:0006629), terpenoid metabolic process (GO:0006721), arachidonate metabolic process (GO:0019369), monocarboxylic acid metabolic process (GO:0032787)

GO Molecular Function (12): monooxygenase activity (GO:0004497), iron ion binding (GO:0005506), arachidonate epoxygenase activity (GO:0008392), retinoic acid 4-hydroxylase activity (GO:0008401), oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen (GO:0016712), heme binding (GO:0020037), caffeine oxidase activity (GO:0034875), estrogen 16-alpha-hydroxylase activity (GO:0101020), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen (GO:0016705), metal ion binding (GO:0046872)

GO Cellular Component (5): cytoplasm (GO:0005737), endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Arachidonate metabolism	2
Cytochrome P450 - arranged by substrate type	1
Xenobiotics	1
Biosynthesis of maresins	1
Drug ADME	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
hormone metabolic process	3
arachidonate metabolic process	2
retinoid metabolic process	2
olefinic compound metabolic process	2
long-chain fatty acid metabolic process	2
icosanoid metabolic process	2
oxidoreductase activity	2
monooxygenase activity	2
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	2
cellular anatomical structure	2
lipid modification	1
metabolic process	1
cellular response to xenobiotic stimulus	1
lipid metabolic process	1
steroid metabolic process	1
xenobiotic metabolic process	1
catabolic process	1
primary alcohol metabolic process	1
monocarboxylic acid metabolic process	1
fatty acid biosynthetic process	1
carboxylic acid biosynthetic process	1
demethylation	1
primary metabolic process	1
isoprenoid metabolic process	1
unsaturated fatty acid metabolic process	1
carboxylic acid metabolic process	1
transition metal ion binding	1
arachidonate monooxygenase activity	1
tetrapyrrole binding	1
oxidoreductase activity, acting on CH or CH2 groups, quinone or similar compound as acceptor	1
steroid hydroxylase activity	1
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen	1
binding	1
catalytic activity	1
cation binding	1
intracellular anatomical structure	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1

Protein interactions and networks

STRING

1688 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CYP2C8	PPIG	Q13427	957
CYP2C8	SLCO1B1	Q9Y6L6	932
CYP2C8	UGT2B7	P16662	817
CYP2C8	VKORC1	Q9BQB6	809
CYP2C8	UGT1A4	P22310	766
CYP2C8	UGT1A6	P19224	732
CYP2C8	UGT1A10	Q9HAW8	720
CYP2C8	UGT1A8	Q9HAW9	719
CYP2C8	UGT1A7	Q9HAW7	718
CYP2C8	UGT1A1	P22309	704
CYP2C8	ABCB1	P08183	701
CYP2C8	EPHX2	P34913	700
CYP2C8	SLC35A2	P78381	700
CYP2C8	SLCO1A2	P46721	681
CYP2C8	UGT1A9	P36509	672

IntAct

22 interactions, top by confidence:

A	B	Type	Score
LAMP2	CYP2C8	psi-mi:“MI:0915”(physical association)	0.560
SH3GLB1	CYP2C8	psi-mi:“MI:0915”(physical association)	0.560
PRPF40A	CYP2C8	psi-mi:“MI:0915”(physical association)	0.560
CYP2C8	EP300	psi-mi:“MI:0915”(physical association)	0.400
PGRMC1	CYP2C8	psi-mi:“MI:0915”(physical association)	0.400
CYP2C8	RIN3	psi-mi:“MI:0915”(physical association)	0.370
A2M	CYP2C8	psi-mi:“MI:0915”(physical association)	0.370
BLMH	CYP2C8	psi-mi:“MI:0915”(physical association)	0.370
APOE	CYP2C8	psi-mi:“MI:0915”(physical association)	0.370
DNAJB1	CYP2C8	psi-mi:“MI:0915”(physical association)	0.370
CYP2C8	LONP1	psi-mi:“MI:0915”(physical association)	0.370
CYP2C8	MAST1	psi-mi:“MI:0915”(physical association)	0.370
MAP1LC3A		psi-mi:“MI:0914”(association)	0.350
GABARAPL1		psi-mi:“MI:0914”(association)	0.350
CYP2C18	PGRMC1	psi-mi:“MI:0914”(association)	0.350

BioGRID (20): CYP2C8 (Two-hybrid), CYP2C8 (Co-crystal Structure), CYP2C8 (Reconstituted Complex), CYP2C8 (Two-hybrid), EP300 (Affinity Capture-MS), CYP2C8 (Affinity Capture-MS), CYP2C8 (Cross-Linking-MS (XL-MS)), CYP2C8 (Cross-Linking-MS (XL-MS)), CYP2C8 (Two-hybrid), BLMH (Two-hybrid), APOE (Two-hybrid), DNAJB1 (Two-hybrid), LONP1 (Two-hybrid), CYP2C8 (Two-hybrid), EXOC6 (Two-hybrid)

ESM2 similar proteins: E9Q5K4, O18809, O35293, O55071, O93297, O93299, P00176, P00178, P00179, P00180, P00181, P04167, P05178, P08683, P10610, P10632, P11371, P11372, P11509, P11712, P12789, P12790, P12791, P15123, P15392, P17666, P20812, P20813, P20852, P20853, P24460, P24461, P24470, P24903, P33260, P33261, P33262, P33263, P33264, P33267

Diamond homologs: A0A087X1C5, E9Q5K4, F1Q8C3, O18809, O18992, O35293, O46658, O54749, O54750, O55071, O62671, O93297, P00176, P00178, P00179, P00180, P00181, P00182, P04167, P05178, P05179, P05180, P05181, P08682, P08683, P10610, P10632, P10633, P10634, P10635, P11371, P11712, P11714, P12789, P12790, P12791, P12938, P12939, P15123, P17666

SIGNOR signaling

0 interactions.

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 2 cancer types — MEL, PLMESO.

Clinical variants and AI predictions

ClinVar

76 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	51
Likely benign	11
Benign	7

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
8411	CYP2C8*5	Pathogenic

SpliceAI

1338 predictions. Top by Δscore:

Variant	Effect	Δscore
10:95042884:GCTTA:G	donor_loss	1.0000
10:95042885:CTTA:C	donor_loss	1.0000
10:95042886:TTACC:T	donor_loss	1.0000
10:95042887:TACC:T	donor_loss	1.0000
10:95042888:ACC:A	donor_loss	1.0000
10:95042889:C:A	donor_loss	1.0000
10:95043078:C:CC	acceptor_gain	1.0000
10:95058329:TCTTA:T	donor_loss	1.0000
10:95058330:CTTA:C	donor_loss	1.0000
10:95058331:TTACC:T	donor_loss	1.0000
10:95058332:TACC:T	donor_loss	1.0000
10:95058333:A:AC	donor_gain	1.0000
10:95058334:C:CC	donor_gain	1.0000
10:95058334:C:CT	donor_loss	1.0000
10:95058334:CCTG:C	donor_gain	1.0000
10:95064794:CCTTA:C	donor_loss	1.0000
10:95064795:CTTAC:C	donor_loss	1.0000
10:95064797:TACC:T	donor_loss	1.0000
10:95064798:A:AG	donor_loss	1.0000
10:95067205:CACC:C	donor_loss	1.0000
10:95067206:AC:A	donor_gain	1.0000
10:95067207:CC:C	donor_gain	1.0000
10:95067222:AACT:A	donor_gain	1.0000
10:95067223:A:C	donor_gain	1.0000
10:95067246:T:TA	donor_gain	1.0000
10:95038896:CCTG:C	donor_gain	0.9900
10:95043073:TTTAG:T	acceptor_gain	0.9900
10:95043075:TAG:T	acceptor_gain	0.9900
10:95043077:GCTGA:G	acceptor_loss	0.9900
10:95043078:C:CA	acceptor_loss	0.9900

AlphaMissense

3255 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:95038904:G:C	F428L	0.994
10:95038904:G:T	F428L	0.994
10:95038906:A:G	F428L	0.994
10:95038952:A:C	F412L	0.992
10:95038952:A:T	F412L	0.992
10:95038954:A:G	F412L	0.992
10:95042968:T:A	R357S	0.992
10:95042968:T:G	R357S	0.992
10:95042991:C:G	A350P	0.992
10:95042969:C:G	R357T	0.990
10:95067294:C:G	R132P	0.990
10:95038985:A:C	F401L	0.989
10:95038985:A:T	F401L	0.989
10:95038987:A:G	F401L	0.989
10:95067311:G:C	F126L	0.988
10:95067311:G:T	F126L	0.988
10:95067313:A:G	F126L	0.988
10:95067244:C:G	A149P	0.987
10:95067318:C:G	R124P	0.982
10:95058351:A:G	L268P	0.981
10:95037309:C:T	G431E	0.980
10:95037263:A:C	F446L	0.979
10:95037263:A:T	F446L	0.979
10:95037265:A:G	F446L	0.979
10:95067285:C:T	G135E	0.979
10:95037309:C:A	G431V	0.978
10:95067255:A:T	V145D	0.978
10:95037298:A:G	C435R	0.977
10:95038953:A:G	F412S	0.977
10:95042990:G:T	A350D	0.977

dbSNP variants (sampled 300 via entrez): RS1000049949 (10:95055013 T>C), RS1000101356 (10:95044332 A>G), RS1000159495 (10:95061349 T>C,G), RS1000199094 (10:95044329 G>C), RS1000200174 (10:95041442 G>A), RS1000257413 (10:95050913 TAACTC>T), RS1000279468 (10:95061223 C>T), RS1000411002 (10:95037595 G>T), RS1000424487 (10:95049013 C>T), RS1000657097 (10:95064293 G>T), RS1000695471 (10:95036466 A>C), RS1000748565 (10:95042949 T>C), RS1000814532 (10:95070616 G>A,T), RS1000835611 (10:95055252 T>C,G), RS1000864055 (10:95044653 C>T)

Disease associations

OMIM: gene MIM:601129 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): pulmonary disease, chronic obstructive, susceptibility to (MONDO:0100167)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST000209_1	Osteonecrosis of the jaw	1.000000e-06
GCST000467_1	Response to clopidogrel therapy	2.000000e-13
GCST001356_24	Gout	1.000000e-07
GCST001491_4	Immune response to smallpox vaccine (IL-6)	5.000000e-07
GCST002061_1	Warfarin maintenance dose	5.000000e-12
GCST002198_21	Tuberculosis	3.000000e-06
GCST007684_2	Plasma clozapine-norclozapine ratio in treatment-resistant schizophrenia	5.000000e-14
GCST009733_189	Urinary metabolite levels in chronic kidney disease	2.000000e-14
GCST011346_61	Total cholesterol levels	8.000000e-09
GCST011347_37	Low density lipoprotein cholesterol levels	2.000000e-08
GCST011742_31	Triglyceride levels in HIV infection	8.000000e-06
GCST012020_579	Serum metabolite levels	1.000000e-11
GCST012020_580	Serum metabolite levels	1.000000e-10
GCST012021_96	Serum metabolite levels	1.000000e-11
GCST012021_97	Serum metabolite levels	1.000000e-10

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0600040	plasma clozapine-to-N-desmethylclozapine ratio measurement
EFO:0005116	urinary metabolite measurement
EFO:0004574	total cholesterol measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3721 (SINGLE PROTEIN), CHEMBL4523986 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

62 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 601,055 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL1064	SIMVASTATIN	4	123,163
CHEMBL1089	PHENELZINE	4	18,793
CHEMBL1200681	MONTELUKAST SODIUM	4	10,913
CHEMBL1276308	MIFEPRISTONE	4	30,535
CHEMBL1479	DANAZOL	4	16,256
CHEMBL1484	NICARDIPINE	4	30,866
CHEMBL157101	KETOCONAZOLE	4	75,361
CHEMBL1648	ISRADIPINE	4	20,026
CHEMBL1873475	IBRUTINIB	4	7,994
CHEMBL2103870	LUMACAFTOR	4	2,367
CHEMBL264241	ANIDULAFUNGIN	4	8,634
CHEMBL3261331	RESMETIROM	4	1,315
CHEMBL3936761	ZANUBRUTINIB	4	2,484
CHEMBL4101807	VOXELOTOR	4	433
CHEMBL445	NORTRIPTYLINE	4	31,234
CHEMBL457	GEMFIBROZIL	4	35,238
CHEMBL480	LANSOPRAZOLE	4	24,317
CHEMBL633	AMIODARONE	4	29,704
CHEMBL6966	VERAPAMIL	4	75,097
CHEMBL787	MONTELUKAST	4
CHEMBL83	TAMOXIFEN	4
CHEMBL998	LORATADINE	4
CHEMBL477772	PAZOPANIB	4
CHEMBL348475	TARIQUIDAR	3
CHEMBL4068611	RELACORILANT	3
CHEMBL4298172	SOTICLESTAT	3
CHEMBL447955	SERLOPITANT	3
CHEMBL50	QUERCETIN	3
CHEMBL146624	MITOGLITAZONE	2

PharmGKB: 1 entry (VIP=true, CPIC=true)

PharmGKB clinical annotations

28 annotations.

Variant	Type	Level	Drugs	Phenotypes
CYP2C81, CYP2C82, CYP2C8*3	Other	3	pioglitazone
CYP2C81, CYP2C82, CYP2C83, CYP2C84	Efficacy	4	ibuprofen	Pain;Postoperative
CYP2C81, CYP2C82, CYP2C83, CYP2C84	Toxicity	4	paclitaxel	Drug Toxicity;Neutropenia;Peripheral Nervous System Diseases;Toxic liver disease
CYP2C81, CYP2C83	Metabolism/PK	3	tacrolimus	Kidney Transplantation
CYP2C81, CYP2C83	Toxicity	3	tacrolimus	Kidney Transplantation
CYP2C81, CYP2C83	Dosage	3	ibuprofen
CYP2C81, CYP2C83	Metabolism/PK	3	rosiglitazone
CYP2C81, CYP2C83	Toxicity	3	rosiglitazone
CYP2C81, CYP2C83	Metabolism/PK	3	ibuprofen
CYP2C81, CYP2C83	Efficacy	3	rosiglitazone
CYP2C81, CYP2C83, CYP2C8*4	Metabolism/PK	3	montelukast	Asthma
CYP2C81, CYP2C83, CYP2C8*4	Metabolism/PK	3	diclofenac
rs10509681	Other	3	paclitaxel
rs10509681	Other	3	repaglinide
rs10509681	Toxicity	3	amodiaquine
rs1058932	Toxicity	3	carboplatin;gemcitabine	Non-Small Cell Lung Carcinoma;Thrombocytopenia
rs1113129	Toxicity	3	paclitaxel
rs1113129	Toxicity	3	paclitaxel	Breast Neoplasms
rs11572076	Toxicity	3	mycophenolate mofetil	Kidney Transplantation
rs11572078	Toxicity	3	carboplatin;gemcitabine	Non-Small Cell Lung Carcinoma;Thrombocytopenia
rs11572080	Other	3	paclitaxel
rs11572080	Dosage	3	repaglinide
rs11572080	Toxicity	3	amodiaquine
rs11572080	Toxicity	3	paclitaxel	Drug Toxicity;Neurotoxicity Syndromes
rs11572103	Dosage	4	paclitaxel
rs117458836	Toxicity	3	cyclophosphamide;epirubicin;fluorouracil	Breast Neoplasms;Neutropenia
rs1934951	Toxicity	4	Bisphosphonates;pamidronate;zoledronate	Multiple Myeloma;Osteonecrosis
rs1934951	Toxicity	4	paclitaxel	Breast Neoplasms

PharmGKB variants

24 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1058930	CYP2C8		0.00	4
rs1113129	CYP2C8	3	2.00	2	paclitaxel
rs1934951	CYP2C8	4	-0.50	2	Bisphosphonates;pamidronate;zoledronate;paclitaxel
rs1934980	CYP2C8		0.00	0
rs2275622	CYP2C8		0.00	0
rs7909236	CYP2C8		0.00	0
rs10509681	CYP2C8	3	1.50	15	repaglinide;amodiaquine;paclitaxel
rs11572076	CYP2C8	3	3.00	1	mycophenolate mofetil
rs11572080	CYP2C8	3	2.00	16	amodiaquine;paclitaxel;repaglinide
rs11572103	CYP2C8	4	-1.25	4	paclitaxel
rs17110453	CYP2C8		0.00	0
rs66501115	CYP2C8		0.00	0
rs72558195	CYP2C8		0.00	0
rs72558196	CYP2C8		0.00	0
rs78637571	CYP2C8		0.00	0
rs142886225	CYP2C8		0.00	0
rs1058932	CYP2C8	3	2.50	1	carboplatin;gemcitabine
rs11572078	CYP2C8	3	2.50	1	carboplatin;gemcitabine
rs769460274	CYP2C8		0.00	0
rs10882526	CYP2C8		0.00	0
rs11572093	CYP2C8		0.00	0
rs1341164	CYP2C8		0.00	0
rs7910936	CYP2C8		0.00	0
rs10882521	CYP2C8		0.00	0

PharmGKB dosing guidelines

1 guidelines.

Source	Drug	Guideline	Dosing?	Recommendation?
CPIC	diclofenac;ibuprofen	Annotation of CPIC Guideline for diclofenac, ibuprofen and CYP2C8

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — CYP2 family: drug metabolising subset

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
compound 51 [Crosignani et al., 2011]	Inhibition	7.37	pIC50
phenelzine	Inhibition	5.14	pKi
voxelotor	Inhibition	5.1	pIC50

Binding affinities (BindingDB)

68 measured of 100 human assays (100 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(2S)-N-[5-[2-(2-methoxy-3-pyridinyl)-7-methylimidazo[1,2-a]pyridin-3-yl]-6-[2-(1-methylisoquinolin-6-yl)ethynyl]-2-pyridinyl]-2-(methylamino)propanamide	IC50	1 nM	US-9481673: 6-alkynyl-pyridine derivatives
(2S)-2-(methylamino)-N-[6-[2-(1-methylisoquinolin-6-yl)ethynyl]-5-[7-methyl-2-(2-methyl-4-pyridinyl)imidazo[1,2-a]pyridin-3-yl]-2-pyridinyl]propanamide	IC50	1 nM	US-9481673: 6-alkynyl-pyridine derivatives
(2S)-2-(methylamino)-N-[6-[2-(1-methylisoquinolin-6-yl)ethynyl]-5-[7-methyl-2-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]-2-pyridinyl]propanamide	IC50	1 nM	US-9481673: 6-alkynyl-pyridine derivatives
(2S)-2-(methylamino)-N-[6-[2-(1-methylisoquinolin-6-yl)ethynyl]-5-[7-methyl-2-(3-methylimidazol-4-yl)imidazo[1,2-a]pyridin-3-yl]-2-pyridinyl]propanamide	IC50	1 nM	US-9481673: 6-alkynyl-pyridine derivatives
(2S)-2-(methylamino)-N-[6-[2-(1-methylisoquinolin-6-yl)ethynyl]-5-[7-methyl-2-(6-methyl-3-pyridinyl)imidazo[1,2-a]pyridin-3-yl]-2-pyridinyl]propanamide	IC50	1 nM	US-9481673: 6-alkynyl-pyridine derivatives
(2S)-2-(methylamino)-N-[6-[2-(1-methylisoquinolin-6-yl)ethynyl]-5-[7-methyl-2-(2-methylpyrimidin-5-yl)imidazo[1,2-a]pyridin-3-yl]-2-pyridinyl]propanamide	IC50	1 nM	US-9481673: 6-alkynyl-pyridine derivatives
(2S)-N-[5-[2-(2-methoxy-4-pyridinyl)-7-methylimidazo[1,2-a]pyridin-3-yl]-6-[2-(1-methylisoquinolin-6-yl)ethynyl]-2-pyridinyl]-2-(methylamino)propanamide	IC50	1 nM	US-9481673: 6-alkynyl-pyridine derivatives
(2S)-N-[5-[2-(6-methoxy-3-pyridinyl)-7-methylimidazo[1,2-a]pyridin-3-yl]-6-[2-(1-methylisoquinolin-6-yl)ethynyl]-2-pyridinyl]-2-(methylamino)propanamide	IC50	1 nM	US-9481673: 6-alkynyl-pyridine derivatives
(2S)-N-[5-[2-(2-methoxy-3-pyridinyl)-7-methylimidazo[1,2-a]pyridin-3-yl]-6-[2-(1-methyl-2-oxoquinolin-6-yl)ethynyl]-2-pyridinyl]-2-(methylamino)propanamide	IC50	1 nM	US-9481673: 6-alkynyl-pyridine derivatives
(2S)-2-(methylamino)-N-[5-[7-methyl-2-(2-methyl-4-pyridinyl)imidazo[1,2-a]pyridin-3-yl]-6-(2-phenylethynyl)-2-pyridinyl]propanamide	IC50	1 nM	US-9481673: 6-alkynyl-pyridine derivatives
(2S)-N-[5-[2-(2-methoxy-4-pyridinyl)-7-methylimidazo[1,2-a]pyridin-3-yl]-6-[2-(1-methyl-2-oxoquinolin-6-yl)ethynyl]-2-pyridinyl]-2-(methylamino)propanamide	IC50	1 nM	US-9481673: 6-alkynyl-pyridine derivatives
(2S)-N-[5-[2-(6-methoxy-3-pyridinyl)-7-methylimidazo[1,2-a]pyridin-3-yl]-6-[2-(1-methyl-2-oxoquinolin-6-yl)ethynyl]-2-pyridinyl]-2-(methylamino)propanamide	IC50	1 nM	US-9481673: 6-alkynyl-pyridine derivatives
(S)-(4-fluorophenyl)-[4-[(5-methylpyrazolidin-3-yl)amino]quinazolin-2-yl]methanol	IC50	1.55 nM	US-9295672: Optically active pyrazolylaminoquinazoline, and pharmaceutical compositions and methods of use thereof
(2S)-2-(methylamino)-N-[6-[2-(1-methylisoquinolin-6-yl)ethynyl]-5-[7-methyl-2-(2-methyl-3-pyridinyl)imidazo[1,2-a]pyridin-3-yl]-2-pyridinyl]propanamide	IC50	2 nM	US-9481673: 6-alkynyl-pyridine derivatives
(2S)-2-(methylamino)-N-[5-[7-methyl-2-(2-methylpyrimidin-5-yl)imidazo[1,2-a]pyridin-3-yl]-6-[2-(1-methyl-2-oxoquinolin-6-yl)ethynyl]-2-pyridinyl]propanamide	IC50	2 nM	US-9481673: 6-alkynyl-pyridine derivatives
(2S)-N-[5-[7-chloro-2-(2-methoxy-3-pyridinyl)imidazo[1,2-a]pyridin-3-yl]-6-[2-(1-methylisoquinolin-6-yl)ethynyl]-2-pyridinyl]-2-(methylamino)propanamide	IC50	2 nM	US-9481673: 6-alkynyl-pyridine derivatives
(2S)-N-[5-[2-(2-methoxy-3-pyridinyl)imidazo[1,2-a]pyridin-3-yl]-6-[2-(1-methylisoquinolin-6-yl)ethynyl]-2-pyridinyl]-2-(methylamino)propanamide	IC50	2 nM	US-9481673: 6-alkynyl-pyridine derivatives
N-[4-[2-(dimethylamino)-1-imidazol-1-ylpropyl]phenyl]-1,3-benzothiazol-2-amine	IC50	4.3 nM	US-9963439: Specific inhibitors of cytochrome P450 26 retinoic acid hydroxylase
R115866	EC50	5 nM
(R)-(4-fluorophenyl)-[4-[(5-methylpyrazolidin-3-yl)amino]quinazolin-2-yl]methanol	IC50	28 nM	US-9295672: Optically active pyrazolylaminoquinazoline, and pharmaceutical compositions and methods of use thereof
1-[4-[4-[[2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]ethanone	IC50	127 nM	US-9394290: Selective CYP11B1 inhibitors for the treatment of cortisol dependent diseases
(4-fluorophenyl)-[4-[(5-methylpyrazolidin-3-yl)amino]quinazolin-2-yl]methanol	KD	1800 nM	US-9295672: Optically active pyrazolylaminoquinazoline, and pharmaceutical compositions and methods of use thereof
Liazal	IC50	1900 nM	US-9963439: Specific inhibitors of cytochrome P450 26 retinoic acid hydroxylase
2-(methylamino)-N-[6-[2-(1-methyl-2-oxoquinolin-6-yl)ethynyl]-5-(7-methyl-2-pyridin-4-ylimidazo[1,2-a]pyridin-3-yl)-2-pyridinyl]propanamide	IC50	2800 nM	US-9481673: 6-alkynyl-pyridine derivatives
2-(methylamino)-N-[6-[2-(4-methyl-3-oxo-1,4-benzoxazin-7-yl)ethynyl]-5-(7-methyl-2-pyridin-4-ylimidazo[1,2-a]pyridin-3-yl)-2-pyridinyl]propanamide	IC50	2900 nM	US-9481673: 6-alkynyl-pyridine derivatives
2-(methylamino)-N-[5-(7-methyl-2-pyridin-4-ylimidazo[1,2-a]pyridin-3-yl)-6-[2-(2-methylquinolin-6-yl)ethynyl]-2-pyridinyl]propanamide	IC50	4300 nM	US-9481673: 6-alkynyl-pyridine derivatives
2-(methylamino)-N-[5-(7-methyl-2-pyridin-4-ylimidazo[1,2-a]pyridin-3-yl)-6-[2-[4-(1,2-oxazol-3-yl)phenyl]ethynyl]-2-pyridinyl]propanamide	IC50	4800 nM	US-9481673: 6-alkynyl-pyridine derivatives
trans-(1S,2S)-2-[5-[[(1R)-4-[2,6-dimethyl-4-(2-methyltetrazol-5-yl)phenyl]-7-fluoro-2,3-dihydro-1H-inden-1-yl]amino]-2-pyridinyl]cyclopropane-1-carboxylic acid	IC50	5000 nM	US-10125101: Indanylaminopyridylcyclopropanecarboxylic acids, pharmaceutical compositions and uses thereof
trans-(1S,2S)-2-[5-[[(1R)-4-(2,6-dimethylphenyl)-7-fluoro-2,3-dihydro-1H-inden-1-yl]amino]-2-pyridinyl]cyclopropane-1-carboxylic acid	IC50	5000 nM	US-10125101: Indanylaminopyridylcyclopropanecarboxylic acids, pharmaceutical compositions and uses thereof
2-(methylamino)-N-[5-(7-methyl-2-pyridin-4-ylimidazo[1,2-a]pyridin-3-yl)-6-(2-quinolin-6-ylethynyl)-2-pyridinyl]propanamide	IC50	5300 nM	US-9481673: 6-alkynyl-pyridine derivatives
trans-(1S,2S)-2-[5-[[(1R)-7-fluoro-4-[4-(3-hydroxy-3-methylbutoxy)-2,6-dimethylphenyl]-2,3-dihydro-1H-inden-1-yl]amino]-2-pyridinyl]cyclopropane-1-carboxylic acid	IC50	6000 nM	US-10125101: Indanylaminopyridylcyclopropanecarboxylic acids, pharmaceutical compositions and uses thereof
trans-(1S,2S)-2-[5-[[(1R)-4-[2,6-dimethyl-4-(2-methylpyrazol-3-yl)phenyl]-7-fluoro-2,3-dihydro-1H-inden-1-yl]amino]-2-pyridinyl]cyclopropane-1-carboxylic acid	IC50	7000 nM	US-10125101: Indanylaminopyridylcyclopropanecarboxylic acids, pharmaceutical compositions and uses thereof
trans-(1S,2S)-2-[5-[[(1R)-7-fluoro-4-[4-(2-methoxy-4-pyridinyl)-2,6-dimethylphenyl]-2,3-dihydro-1H-inden-1-yl]amino]-2-pyridinyl]cyclopropane-1-carboxylic acid	IC50	8000 nM	US-10125101: Indanylaminopyridylcyclopropanecarboxylic acids, pharmaceutical compositions and uses thereof
trans-(1S,2S)-2-[5-[[(1R)-4-(3-cyano-2-methylphenyl)-7-fluoro-2,3-dihydro-1H-inden-1-yl]amino]-2-pyridinyl]cyclopropane-1-carboxylic acid	IC50	9000 nM	US-10125101: Indanylaminopyridylcyclopropanecarboxylic acids, pharmaceutical compositions and uses thereof
trans-(1S,2S)-2-[5-[[(1R)-7-fluoro-4-(2-propan-2-ylphenyl)-2,3-dihydro-1H-inden-1-yl]amino]-2-pyridinyl]cyclopropane-1-carboxylic acid	IC50	10000 nM	US-10125101: Indanylaminopyridylcyclopropanecarboxylic acids, pharmaceutical compositions and uses thereof
trans-(1S,2S)-2-[5-[[(1R)-7-fluoro-4-[4-[(2-hydroxy-2-methylpropyl)carbamoyl]-2,6-dimethylphenyl]-2,3-dihydro-1H-inden-1-yl]amino]-2-pyridinyl]cyclopropane-1-carboxylic acid	IC50	10000 nM	US-10125101: Indanylaminopyridylcyclopropanecarboxylic acids, pharmaceutical compositions and uses thereof
trans-(1S,2S)-2-[5-[[(1R)-4-(2,6-dichlorophenyl)-7-fluoro-2,3-dihydro-1H-inden-1-yl]amino]-2-pyridinyl]cyclopropane-1-carboxylic acid	IC50	11000 nM	US-10125101: Indanylaminopyridylcyclopropanecarboxylic acids, pharmaceutical compositions and uses thereof
trans-(1S,2S)-2-[5-[[(1R)-4-[2,6-dimethyl-4-(3-methylsulfonylpropoxy)phenyl]-7-fluoro-2,3-dihydro-1H-inden-1-yl]amino]-2-pyridinyl]cyclopropane-1-carboxylic acid	IC50	12000 nM	US-10125101: Indanylaminopyridylcyclopropanecarboxylic acids, pharmaceutical compositions and uses thereof
trans-(1S,2S)-2-[5-[[(1R)-4-[2,6-dimethyl-4-(oxan-4-ylmethoxy)phenyl]-7-fluoro-2,3-dihydro-1H-inden-1-yl]amino]-2-pyridinyl]cyclopropane-1-carboxylic acid	IC50	14000 nM	US-10125101: Indanylaminopyridylcyclopropanecarboxylic acids, pharmaceutical compositions and uses thereof
trans-(1S,2S)-2-[5-[[(1R)-4-[2,6-dimethyl-4-(1-methyl-2-oxo-4-pyridinyl)phenyl]-7-fluoro-2,3-dihydro-1H-inden-1-yl]amino]-2-pyridinyl]cyclopropane-1-carboxylic acid	IC50	14000 nM	US-10125101: Indanylaminopyridylcyclopropanecarboxylic acids, pharmaceutical compositions and uses thereof
trans-(1S,2S)-2-[5-[[(1R)-4-[2,6-dimethyl-4-(5-methylpyrimidin-2-yl)phenyl]-7-fluoro-2,3-dihydro-1H-inden-1-yl]amino]-2-pyridinyl]cyclopropane-1-carboxylic acid	IC50	15000 nM	US-10125101: Indanylaminopyridylcyclopropanecarboxylic acids, pharmaceutical compositions and uses thereof
trans-(1S,2S)-2-[5-[[(1R)-7-fluoro-4-[2-(trifluoromethyl)phenyl]-2,3-dihydro-1H-inden-1-yl]amino]-2-pyridinyl]cyclopropane-1-carboxylic acid	IC50	15000 nM	US-10125101: Indanylaminopyridylcyclopropanecarboxylic acids, pharmaceutical compositions and uses thereof
(2S,5S,8S)-14-methoxy-5-methyl-2-(2-methylpropyl)-3,6,17-triazatetracyclo[8.7.0.03,8.011,16]heptadeca-1(10),11,13,15-tetraene-4,7-dione	IC50	15400 nM	US-9695174: Inhibitor of breast cancer resistance protein (BCRP)
2-(methylamino)-N-[5-(7-methyl-2-pyridin-4-ylimidazo[1,2-a]pyridin-3-yl)-6-(2-phenylethynyl)-2-pyridinyl]propanamide	IC50	16000 nM	US-9481673: 6-alkynyl-pyridine derivatives
3-{[(2R)-4-methylmorpholin-2-yl]methoxy}-5-(5-methyl-1,3-thiazol-2-yl)-N-{(1R)-1-[2-(trifluoromethyl)pyrimidin-5-yl]ethyl}benzamide	IC50	18000 nM	US-10202369: 1,3-thiazol-2-yl substituted benzamides
trans-(1S,2S)-2-[5-[[(1R)-4-[2,6-dimethyl-4-(1-methyl-6-oxopiperidin-3-yl)phenyl]-7-fluoro-2,3-dihydro-1H-inden-1-yl]amino]-2-pyridinyl]cyclopropane-1-carboxylic acid	IC50	19000 nM	US-10125101: Indanylaminopyridylcyclopropanecarboxylic acids, pharmaceutical compositions and uses thereof
trans-(1S,2S)-2-[5-[[(1R)-4-[4-(2-cyano-2-methylpropoxy)-2,6-dimethylphenyl]-7-fluoro-2,3-dihydro-1H-inden-1-yl]amino]-2-pyridinyl]cyclopropane-1-carboxylic acid	IC50	19000 nM	US-10125101: Indanylaminopyridylcyclopropanecarboxylic acids, pharmaceutical compositions and uses thereof
trans-(1S,2S)-2-[5-[[(1R)-7-fluoro-4-[4-(3-hydroxy-3-methylbutoxy)-2,6-dimethylphenyl]-2,3-dihydro-1H-inden-1-yl]amino]-2-pyridinyl]cyclopropane-1-carboxylic acid	IC50	20000 nM	US-10125101: Indanylaminopyridylcyclopropanecarboxylic acids, pharmaceutical compositions and uses thereof
trans-(1S,2S)-2-[5-[[(1R)-4-[4-(5-methoxypyrazin-2-yl)phenyl]-2,3-dihydro-1H-inden-1-yl]amino]-2-pyridinyl]cyclopropane-1-carboxylic acid	IC50	20000 nM	US-10125101: Indanylaminopyridylcyclopropanecarboxylic acids, pharmaceutical compositions and uses thereof
trans-(1S,2S)-2-[5-[[(1R)-4-[2,6-dimethyl-4-(2-methyltetrazol-5-yl)phenyl]-7-fluoro-2,3-dihydro-1H-inden-1-yl]amino]-2-pyridinyl]cyclopropane-1-carboxylic acid	IC50	20000 nM	US-10125101: Indanylaminopyridylcyclopropanecarboxylic acids, pharmaceutical compositions and uses thereof

ChEMBL bioactivities

339 potent at pChembl≥5 of 530 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.60	IC50	2.5	nM	CHEMBL4577468
7.66	Ki	22	nM	CHEMBL4066318
7.58	IC50	26	nM	CHEMBL4086080
7.37	IC50	43	nM	CHEMBL2036213
7.30	IC50	50	nM	CHEMBL2036225
7.28	Ki	52.1	nM	CHEMBL4066318
7.27	IC50	54	nM	CHEMBL2036220
7.25	IC50	56.5	nM	MONTELUKAST
7.10	IC50	79	nM	CHEMBL2036222
7.10	IC50	79.43	nM	CHEMBL4446613
7.07	IC50	86	nM	CHEMBL2036210
7.00	IC50	100	nM	CHEMBL4242598
7.00	IC50	100	nM	CHEMBL4437930
6.92	IC50	120	nM	CHEMBL2413882
6.89	IC50	130	nM	MONTELUKAST
6.80	IC50	160	nM	MONTELUKAST
6.75	IC50	180	nM	CHEMBL3810042
6.68	IC50	210	nM	RELACORILANT
6.66	IC50	220	nM	CHEMBL2036223
6.66	IC50	220	nM	CHEMBL2413881
6.66	IC50	220	nM	CHEMBL5590455
6.66	IC50	220	nM	TALAROZOLE
6.60	IC50	250	nM	CHEMBL2018923
6.60	IC50	251.2	nM	CHEMBL601428
6.58	IC50	260	nM	CHEMBL4169721
6.57	IC50	270	nM	CHEMBL5279540
6.52	IC50	300	nM	CHEMBL3925961
6.52	IC50	300	nM	CHEMBL3969750
6.50	IC50	320	nM	CHEMBL2036017
6.50	IC50	316.2	nM	CHEMBL4102696
6.46	IC50	350	nM	CHEMBL4096241
6.40	IC50	400	nM	CHEMBL2425146
6.40	IC50	398.1	nM	CHEMBL4084771
6.40	IC50	400	nM	CHEMBL6191738
6.34	IC50	456	nM	CHEMBL3627894
6.33	IC50	470	nM	CHEMBL2036030
6.32	IC50	480	nM	LIAROZOLE
6.30	IC50	500	nM	CHEMBL3910478
6.30	IC50	501.2	nM	CHEMBL5437247
6.29	IC50	510	nM	CHEMBL502335
6.28	IC50	530	nM	CHEMBL5412197
6.24	IC50	570	nM	CHEMBL2036203
6.23	IC50	590	nM	CHEMBL5086239
6.20	IC50	631	nM	CHEMBL4526347
6.17	IC50	680	nM	CHEMBL2018926
6.17	IC50	680	nM	CHEMBL3934548
6.16	IC50	700	nM	CHEMBL4537998
6.16	IC50	700	nM	CHEMBL3330409
6.16	IC50	700	nM	CHEMBL6191009
6.10	IC50	800	nM	CHEMBL3114608

PubChem BioAssay actives

307 with measured affinity, of 2024 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-[[[5-[5-(6-chloro-1H-benzimidazol-2-yl)-2-pyridinyl]-2-pyridinyl]amino]methyl]benzoic acid	1593780: Inhibition of CYP2C8 (unknown origin)	ic50	0.0025	uM
(2S,3S,4S,5R,6S)-6-[(E)-3-[2-[1-[[2-(5-bromopyrimidin-2-yl)-3-cyclopentyl-1-methylindole-6-carbonyl]amino]cyclobutyl]-3-methylbenzimidazol-5-yl]prop-2-enoyl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid	1450607: Reversible inhibition of CYP2C8 in human liver microsomes after 5 mins by LC-MS/MS analysis	ki	0.0220	uM
2-(4-fluorophenyl)-N-methyl-5-[2-methyl-5-[(1-pyridin-4-ylcyclopropyl)carbamoyl]phenyl]-1-benzofuran-3-carboxamide	1447779: Inhibition of microsomal CYP2C8 (unknown origin)	ic50	0.0260	uM
8-imidazol-1-yl-5,6,7,8-tetrahydroquinoline	2022035: Inhibition of CYP450 (unknown origin)	ic50	0.0335	uM
N-[3-fluoro-5-(2H-tetrazol-5-yl)phenyl]-N-[[4-(trifluoromethoxy)phenyl]methyl]propanamide	664814: Inhibition of human recombinant CYP2C8 incubated for 15 mins prior to substrate addition measured after 30 mins by spectrophotometry	ic50	0.0430	uM
N-[3-fluoro-5-(2H-tetrazol-5-yl)phenyl]-N-[(4-methylsulfonylphenyl)methyl]-2-phenylacetamide	664814: Inhibition of human recombinant CYP2C8 incubated for 15 mins prior to substrate addition measured after 30 mins by spectrophotometry	ic50	0.0500	uM
N-[3-fluoro-5-(2H-tetrazol-5-yl)phenyl]-N-[(4-methylsulfonylphenyl)methyl]propanamide	664814: Inhibition of human recombinant CYP2C8 incubated for 15 mins prior to substrate addition measured after 30 mins by spectrophotometry	ic50	0.0540	uM
N-[3-fluoro-5-(2H-tetrazol-5-yl)phenyl]-3-methyl-N-[(4-methylsulfonylphenyl)methyl]butanamide	664814: Inhibition of human recombinant CYP2C8 incubated for 15 mins prior to substrate addition measured after 30 mins by spectrophotometry	ic50	0.0790	uM
6-(2,4-difluorophenyl)-N-pyridin-4-yl-1H-pyrrolo[2,3-b]pyridin-4-amine	1627675: Inhibition of CYP2C8 (unknown origin)	ic50	0.0794	uM
N-[3-fluoro-5-(2H-tetrazol-5-yl)phenyl]-N-[[4-(trifluoromethyl)phenyl]methyl]propanamide	664814: Inhibition of human recombinant CYP2C8 incubated for 15 mins prior to substrate addition measured after 30 mins by spectrophotometry	ic50	0.0860	uM
2-(4-phenoxyphenoxy)-6-[(1S,4S)-5-prop-2-enoyl-2,5-diazabicyclo[2.2.1]heptan-2-yl]pyridine-3-carboxamide	1399794: Inhibition of CYP2C8 (unknown origin)	ic50	0.1000	uM
6-(5-chloro-2,4-difluorophenyl)-N-pyridin-4-yl-1H-pyrrolo[2,3-b]pyridin-4-amine	1627675: Inhibition of CYP2C8 (unknown origin)	ic50	0.1000	uM
(E)-3-[4-[(E)-2-(2-chloro-4-fluorophenyl)-1-(1H-indazol-5-yl)but-1-enyl]phenyl]prop-2-enoic acid	1228278: Inhibition of CYP2C8 (unknown origin)	ic50	0.1000	uM
N-[3-[(1-tert-butyltetrazol-5-yl)-pyrrolidin-1-ylmethyl]phenyl]-7-chloroquinolin-4-amine	765159: Inhibition of CYP2C8 in human liver microsomes assessed as paclitaxel 6alpha-hydroxylation after 20 mins by LC-MS analysis	ic50	0.1200	uM
Montelukast	1911194: Inhibition of CYP2C8 in human liver microsomes using paclitaxel as substrate incubated for 5 to 45 mins in presence of NADPH by LC/MS analysis	ic50	0.1300	uM
N-[2-oxo-1-[2-[propan-2-yloxy-[3-(trifluoromethyl)phenyl]methyl]-1H-imidazol-5-yl]-4-pyridinyl]-1,3-thiazole-4-carboxamide	1304154: Inhibition of CYP2C8 (unknown origin)	ic50	0.1800	uM
[(4aR)-1-(4-fluorophenyl)-6-(1-methylpyrazol-4-yl)sulfonyl-4,5,7,8-tetrahydropyrazolo[5,4-g]isoquinolin-4a-yl]-[4-(trifluoromethyl)-2-pyridinyl]methanone	1482067: Inhibition of CYP2C8 (unknown origin)	ic50	0.2100	uM
2-[[4-[6-[[2-fluoro-4-(oxetan-3-yl)phenyl]methoxy]-2-pyridinyl]piperidin-1-yl]methyl]-3-[[(2S)-oxetan-2-yl]methyl]benzimidazole-5-carboxylic acid	2117589: Inhibition of CYP2C8 in human liver microsomes using paclitaxel as substrate preincubated for 5 mins followed by NADPH addition and measured after 20 mins by LC-MS/MS analysis	ic50	0.2200	uM
N-[3-fluoro-5-(2H-tetrazol-5-yl)phenyl]-N-[(4-methylsulfonylphenyl)methyl]cyclopentanecarboxamide	664814: Inhibition of human recombinant CYP2C8 incubated for 15 mins prior to substrate addition measured after 30 mins by spectrophotometry	ic50	0.2200	uM
N-[3-[(1-tert-butyltetrazol-5-yl)-(diethylamino)methyl]phenyl]-7-chloroquinolin-4-amine	765159: Inhibition of CYP2C8 in human liver microsomes assessed as paclitaxel 6alpha-hydroxylation after 20 mins by LC-MS analysis	ic50	0.2200	uM
6-methoxy-2-[(3-phenylphenyl)methylsulfanyl]-1H-benzimidazole	656028: Inhibition of CYP2C8 in human liver microsomes using paclitaxel as substrate preincubated for 5 mins by LC-MS/MS analysis	ic50	0.2500	uM
N-(4-chlorophenyl)-5-ethyl-N-methyl-3-phenyl-1,2-oxazole-4-carboxamide	2108148: Inhibition of CYP450 (unknown origin)	ic50	0.2512	uM
[5-(4-propyl-3-pyridinyl)furan-2-yl]methanamine;dihydrochloride	1356006: Inhibition of CYP2C8 in human liver microsomes using amodiaquine as substrate preincubated for 5 mins followed by addition of NADPH-regenerating system and measured after 15 mins by UPLC-MS analysis	ic50	0.2600	uM
1-[(3S)-2,2-bis(ethenyl)-3-phenyl-5-[2-(2H-tetrazol-5-yl)phenyl]-3H-1-benzofuran-7-yl]-3-(4-methylphenyl)urea	1955443: Inhibition of CYP2C8 (unknown origin)	ic50	0.2700	uM
N-[2-(2,5-difluorophenyl)-5-methyl-4-pyridinyl]-1H-pyrazolo[4,3-b]pyridin-7-amine	1444765: Inhibition of CYP2C8 (unknown origin)	ic50	0.3162	uM
N-[(4-methoxyphenyl)methyl]-N-[3-(2H-tetrazol-5-yl)phenyl]pentanamide	664814: Inhibition of human recombinant CYP2C8 incubated for 15 mins prior to substrate addition measured after 30 mins by spectrophotometry	ic50	0.3200	uM
2-(4-fluorophenyl)-N-methyl-5-[2-methyl-5-[(1-pyridin-3-ylcyclopropyl)carbamoyl]phenyl]-1-benzofuran-3-carboxamide	1447779: Inhibition of microsomal CYP2C8 (unknown origin)	ic50	0.3500	uM
N-[2-(5-chloro-2-fluorophenyl)-5-methyl-4-pyridinyl]-1H-pyrazolo[4,3-b]pyridin-7-amine	1444765: Inhibition of CYP2C8 (unknown origin)	ic50	0.3981	uM
2-[3-[4-(2-chloro-4-hydroxyphenyl)phenyl]propanoylamino]benzoic acid	304081: Inhibition of CYP2C8 in human liver microsomes	ic50	0.4000	uM
1-[3-tert-butyl-1-(4-methylphenyl)pyrazol-5-yl]-3-(4-imidazol-1-ylphenyl)urea	770853: Inhibition of CYP2C8 (unknown origin)	ic50	0.4000	uM
2,6-dichloro-N-[(2R)-2-(6-chloro-5-methoxy-1H-benzimidazol-2-yl)-2-(3-fluorophenyl)ethyl]-4-(3-methyl-1,2,4-triazol-1-yl)benzamide	1252157: Inhibition of CYP2C8 (unknown origin)	ic50	0.4560	uM
N-[3-fluoro-5-(2H-tetrazol-5-yl)phenyl]-N-[(3-propan-2-yloxyphenyl)methyl]propanamide	664814: Inhibition of human recombinant CYP2C8 incubated for 15 mins prior to substrate addition measured after 30 mins by spectrophotometry	ic50	0.4700	uM
17-chloro-12-[2-(2-methoxyethoxy)ethyl]-5,14,22-trimethyl-28-oxa-2,9-dithia-5,6,12,13,24-pentazaheptacyclo[27.7.1.14,7.011,15.016,21.020,24.030,35]octatriaconta-1(36),4(38),6,11(15),13,16,18,20,22,29(37),30,32,34-tridecaene-23-carboxylic acid	2031297: Inhibition of human CYP2C8 assessed as fluorescent metabolites by CYP450 inhibition assay	ic50	0.5012	uM
6-methoxy-2-(naphthalen-2-ylmethylsulfanyl)-1H-benzimidazole	656028: Inhibition of CYP2C8 in human liver microsomes using paclitaxel as substrate preincubated for 5 mins by LC-MS/MS analysis	ic50	0.5100	uM
(3R)-1’-[3-(3,4-dihydro-2H-1,5-naphthyridin-1-yl)-1H-pyrazolo[3,4-b]pyrazin-6-yl]spiro[3H-1-benzofuran-2,4’-piperidine]-3-amine;hydrochloride	2016488: Reversible inhibition of CYP2C8 in human liver microsomes	ic50	0.5300	uM
N-(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)-N-[3-(2H-tetrazol-5-yl)phenyl]pentanamide	664814: Inhibition of human recombinant CYP2C8 incubated for 15 mins prior to substrate addition measured after 30 mins by spectrophotometry	ic50	0.5700	uM
4-(1-benzofuran-2-yl)-2-[1-(3H-imidazo[4,5-c]pyridin-2-ylmethyl)piperidin-4-yl]-1,3-thiazole	1827337: Inhibition of CYP2C8 in human liver microsomes using amodiaquine as substrate by LC-MS/MS analysis	ic50	0.5900	uM
6-(3,4-difluorophenyl)-N-pyridin-4-yl-1H-pyrrolo[2,3-b]pyridin-4-amine	1627675: Inhibition of CYP2C8 (unknown origin)	ic50	0.6310	uM
4-[(3R)-3-(4-fluorophenyl)sulfonyl-3-[4-(1,1,1,2,3,3,3-heptafluoropropan-2-yl)phenyl]pyrrolidine-1-carbonyl]cyclohexane-1-carboxylic acid	1542634: Inhibition of CYP2C8 (unknown origin)	ic50	0.6800	uM
6-methoxy-2-[(4-phenylmethoxyphenyl)methylsulfanyl]-1H-benzimidazole	656028: Inhibition of CYP2C8 in human liver microsomes using paclitaxel as substrate preincubated for 5 mins by LC-MS/MS analysis	ic50	0.6800	uM
2-(dimethylamino)-2-(2-ethylphenyl)-N-[3-(3-sulfamoylphenyl)-1H-indazol-5-yl]acetamide	2119433: Inhibition of CYP450 (unknown origin)	ic50	0.7000	uM
(5S)-5-(4-chlorophenyl)-N-[4-(4-fluorophenoxy)phenyl]-7,8-dihydro-5H-1,6-naphthyridine-6-carboxamide	1527211: Inhibition of CYP2C8 in human liver microsomes using amodiaquine as substrate by LC-MS/MS analysis	ic50	0.7000	uM
3-[2-[(4aR,7aR)-3,4a,5,6,7,7a-hexahydro-2H-cyclopenta[b][1,4]oxazin-4-yl]-4-(5-chloro-3-pyridinyl)-3-[(4-methylcyclohexyl)methyl]imidazo[4,5-c]pyridin-6-yl]-4H-1,2,4-oxadiazol-5-one	1807809: Inhibition of CYP2C8 (unknown origin)	ic50	0.8000	uM
(6aS)-5-(4-hydroxycyclohexyl)-6a-methyl-2-(7-methyl-1H-indol-3-yl)-9,10-dihydro-7H-[1,4]oxazino[3,4-h]pteridin-6-one	2021634: Inhibition of CYP2C8 (unknown origin)	ic50	0.8000	uM
N-[(1S,2R)-2-phenylcyclopropyl]-4-[4-(2H-tetrazol-5-yl)phenoxy]piperidine-1-carboxamide	1067393: Inhibition of CYP2C8 in human liver microsomes after 10 mins by LC/MS/MS analysis	ic50	0.8000	uM
Clotrimazole	1210016: Inhibition of CYP2C8 in human liver microsomes using paclitaxel as substrate after 8 mins by LC-MS/MS analysis	ic50	0.8030	uM
1-[4-[(1R)-1-[2-[[6-[6-(dimethylamino)pyrimidin-4-yl]-1H-benzimidazol-2-yl]amino]-4-pyridinyl]ethyl]piperazin-1-yl]-3,3,3-trifluoropropan-1-one	1582179: Inhibition of CYP2C8 (unknown origin)	ic50	0.8600	uM
1-[5-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)-2,3-dihydroindol-1-yl]-2-[3-(trifluoromethyl)phenyl]ethanone	777373: Inhibition of CYP2C8 in human liver microsomes using paclitaxel as substrate after 5 to 60 mins by LC-MS/MS analysis	ic50	0.8900	uM
2-pyrrolidin-1-yl-N-[3-(3-sulfamoylphenyl)-1H-indazol-5-yl]-2-thiophen-3-ylacetamide	2119433: Inhibition of CYP450 (unknown origin)	ic50	0.9000	uM
Resmetirom	2123726: Inhibition of CYP2C8 in human liver microsomes at 10 uM in presence of NADPH	ic50	0.9000	uM

CTD chemical–gene interactions

213 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Paclitaxel	increases response to substance, affects metabolic processing, increases hydroxylation, increases oxidation, decreases reaction (+2 more)	14
Amodiaquine	decreases reaction, decreases expression, decreases activity, increases secretion, increases chemical synthesis (+8 more)	12
Rifampin	affects binding, increases response to substance, decreases expression, increases activity, decreases reaction (+1 more)	10
montelukast	increases metabolic processing, decreases activity	7
Rosiglitazone	increases metabolic processing, decreases activity, decreases expression, decreases metabolic processing, affects metabolic processing	7
Quercetin	decreases reaction, increases metabolic processing, increases abundance, affects cotreatment, decreases activity (+1 more)	7
Chloroquine	affects metabolic processing, increases metabolic processing, increases abundance, decreases reaction	5
Gemfibrozil	decreases activity, affects metabolic processing, decreases reaction, affects chemical synthesis, decreases chemical synthesis (+3 more)	5
desethylamodiaquine	increases chemical synthesis, increases abundance, increases metabolic processing, increases secretion	4
Carbamazepine	affects metabolic processing, increases metabolic processing, increases reaction, increases expression	4
desethylchloroquine	increases metabolic processing, decreases reaction, increases abundance	3
perfluorooctane sulfonic acid	decreases reaction, increases hydroxylation, increases expression	3
cerivastatin	affects response to substance, increases metabolic processing	3
Pioglitazone	decreases reaction, decreases activity, increases expression, affects metabolic processing	3
Troglitazone	increases metabolic processing, decreases activity, increases expression	3
Acetaminophen	affects cotreatment, decreases expression	3
Amiodarone	decreases activity, decreases response to substance, increases metabolic processing, decreases reaction	3
Chenodeoxycholic Acid	affects cotreatment, decreases expression	3
Ibuprofen	affects metabolic processing, decreases metabolic processing, increases metabolic processing	3
Ketoconazole	affects cotreatment, affects reaction, increases metabolic processing, decreases activity	3
Phenobarbital	increases expression	3
Fenofibrate	affects expression, decreases activity, increases expression	3
Tretinoin	affects metabolic processing, increases hydroxylation, increases metabolic processing	3
Aflatoxin B1	affects expression, decreases expression, decreases methylation	3
bisphenol A	decreases activity, increases glutathionylation, increases hydroxylation	2
sodium arsenite	decreases expression	2
Clotrimazole	decreases activity	2
Clozapine	increases metabolic processing	2
Deoxycholic Acid	affects cotreatment, decreases expression	2
Dexamethasone	affects binding, increases expression	2

ChEMBL screening assays

1025 unique, capped per target: 1005 admet, 19 binding, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1001843	ADMET	Inhibition of CYP2C8	Tetrahydro anthranilic acid as a surrogate for anthranilic acid: application to the discovery of potent niacin receptor agonists. — Bioorg Med Chem Lett
CHEMBL2422741	Binding	Inhibition of human CYP2C8 at 10 uM	Spirolactam-based acetyl-CoA carboxylase inhibitors: toward improved metabolic stability of a chromanone lead structure. — J Med Chem
CHEMBL5043018	Toxicity	Inhibition of CYP2C8 in human liver microsome at 10 uM	3CL Protease Inhibitors with an Electrophilic Arylketone Moiety as Anti-SARS-CoV-2 Agents. — J Med Chem

Cellosaurus cell lines

5 cell lines: 4 transformed cell line, 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B5W0	Hepc/2C8.46	Cancer cell line	Male
CVCL_UG90	HEK293 CYP2C8*1-V5	Transformed cell line	Female
CVCL_UG91	HEK293 CYP2C8*2-V5	Transformed cell line	Female
CVCL_UG92	HEK293 CYP2C8*3-V5	Transformed cell line	Female
CVCL_UG93	HEK293 CYP2C8*4-V5	Transformed cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.