CYP2C9

Summary

CYP2C9 (cytochrome P450 family 2 subfamily C member 9, HGNC:2623) is a protein-coding gene on chromosome 10q23.33, encoding Cytochrome P450 2C9 (P11712). A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids and steroids.

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 rifampin. The enzyme is known to metabolize many xenobiotics, including phenytoin, tolbutamide, ibuprofen and S-warfarin. Studies identifying individuals who are poor metabolizers of phenytoin and tolbutamide suggest that this gene is polymorphic. The gene is located within a cluster of cytochrome P450 genes on chromosome 10q24.

Source: NCBI Gene 1559 — RefSeq curated summary.

At a glance

• GWAS associations: 20
• Clinical variants (ClinVar): 58 total — 1 pathogenic
• Phenotypes (HPO): 2
• Druggable target: yes — 357 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000771

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2623
Approved symbol	CYP2C9
Name	cytochrome P450 family 2 subfamily C member 9
Location	10q23.33
Locus type	gene with protein product
Status	Approved
Aliases	P450IIC9
Ensembl gene	ENSG00000138109
Ensembl biotype	protein_coding
OMIM	601130
Entrez	1559

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 18 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000260682, ENST00000461906, ENST00000473496, ENST00000643112, ENST00000645207, ENST00000880946, ENST00000880947, ENST00000880948, ENST00000880949, ENST00000880950, ENST00000880951, ENST00000880952, ENST00000880953, ENST00000880954, ENST00000880955, ENST00000880956, ENST00000880957, ENST00000880958, ENST00000880959, ENST00000880960, ENST00000880961

RefSeq mRNA: 1 — MANE Select: NM_000771 NM_000771

CCDS: CCDS7437

Canonical transcript exons

ENST00000260682 — 9 exons

Exon	Start	End
ENSE00001162173	94988847	94990091
ENSE00002442427	94986033	94986174
ENSE00002448359	94972104	94972245
ENSE00002454713	94981183	94981370
ENSE00002485068	94949108	94949284
ENSE00002700597	94938658	94938850
ENSE00003593739	94941858	94942020
ENSE00003599164	94942192	94942341
ENSE00003670754	94947779	94947939

Expression profiles

Bgee: expression breadth ubiquitous, 157 present calls, max score 99.54.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 3.6743 / max 1368.1893, expressed in 30 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
106345	3.5608	20
106347	0.1133	21
106346	0.0002	0

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	99.54	gold quality
jejunal mucosa	UBERON:0000399	99.00	gold quality
liver	UBERON:0002107	98.10	gold quality
pancreatic ductal cell	CL:0002079	96.89	gold quality
ileal mucosa	UBERON:0000331	96.84	gold quality
duodenum	UBERON:0002114	96.21	gold quality
tongue squamous epithelium	UBERON:0006919	90.70	silver quality
cervix squamous epithelium	UBERON:0006922	89.34	gold quality
gall bladder	UBERON:0002110	87.44	gold quality
lower esophagus mucosa	UBERON:0035834	86.67	gold quality
small intestine	UBERON:0002108	86.01	gold quality
small intestine Peyer’s patch	UBERON:0003454	86.00	gold quality
epithelial cell of pancreas	CL:0000083	85.15	silver quality
jejunum	UBERON:0002115	83.06	gold quality
squamous epithelium	UBERON:0006914	82.84	silver quality
gingival epithelium	UBERON:0001949	81.78	silver quality
epithelium of esophagus	UBERON:0001976	80.71	silver quality
esophagus squamous epithelium	UBERON:0006920	80.19	gold quality
body of stomach	UBERON:0001161	79.42	gold quality
mucosa of stomach	UBERON:0001199	79.40	gold quality
esophagus mucosa	UBERON:0002469	79.08	gold quality
gingiva	UBERON:0001828	77.61	silver quality
stomach	UBERON:0000945	76.88	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.46	gold quality
pylorus	UBERON:0001166	75.90	gold quality
mucosa of transverse colon	UBERON:0004991	73.43	gold quality
endometrium epithelium	UBERON:0004811	72.36	gold quality
fundus of stomach	UBERON:0001160	71.76	gold quality
epithelium of nasopharynx	UBERON:0001951	70.68	gold quality
cardia of stomach	UBERON:0001162	70.34	silver quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-100618	yes	1577.97
E-HCAD-9	yes	59.56
E-ANND-3	yes	16.59

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, ESR1, FOS, FOXA3, FOXC1, GATA2, GATA4, HNF1A, HNF4A, JUND, MYC, NCOA1, NCOA6, NFE2L2, NR1I2, NR1I3, NR3C1, PPARA, PPARGC1A, RORA, RORC, SUPT20H, TCF3, VDR

miRNA regulators (miRDB)

30 targeting CYP2C9, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-143-3P	99.49	69.05	1457
HSA-MIR-4770	99.49	69.09	1451
HSA-MIR-365A-3P	99.43	70.02	836
HSA-MIR-365B-3P	99.43	70.02	836
HSA-MIR-183-3P	99.41	69.41	1598
HSA-MIR-4797-5P	99.39	68.01	1354
HSA-MIR-155-5P	99.35	70.16	1509
HSA-MIR-542-3P	99.34	67.58	1270
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-3606-5P	99.31	69.67	1168
HSA-MIR-6088	99.29	68.45	1284
HSA-MIR-4426	99.17	66.74	1949
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-1843	98.97	66.07	838
HSA-MIR-4802-5P	98.97	66.26	833
HSA-MIR-4501	98.72	67.19	921
HSA-MIR-532-5P	98.43	67.53	760
HSA-MIR-1279	97.83	67.50	1898
HSA-MIR-7161-3P	96.79	68.79	798
HSA-MIR-552-3P	96.68	64.12	1026
HSA-MIR-12128	96.67	66.98	1471

Literature-anchored findings (GeneRIF, showing 40)

• polymorphic alleles are rare in Inuit population (PMID:11697742)
• Identification of a null allele of CYP2C9 in an African-American exhibiting toxicity to phenytoin (PMID:11740344)
• Cytochrome P4502C9 genotype in southeast anatolia and possible relation with some serum tumour markers and cytokines. (PMID:11833786)
• Anti-cytochrome P450 autoantibodies, identified on the basis of their specific binding in immunoblots, are significantly increased among children on immunosuppressive drugs and in some cases are associated with drug toxicity and organ rejection. (PMID:11876753)
• Influence of cytochrome P450 CYP2C9 genotypes in lung cancer risk. (PMID:11911968)
• CYP2C9*2 and CYP2C9*3 polymorphisms are associated with an increased risk of overanticoagulation and of bleeding events among patients in a warfarin anticoagulation clinic setting (PMID:11926893)
• Association of CYP2C9 genotypes leading to high enzyme activity and colorectal cancer risk. (PMID:11960920)
• expression in hepatocytes by vitamin D receptor pathway (PMID:11991950)
• 2C9*3 and 2C9*2 variants of cytochrome P-450 CYP2C9 show a different sensitivity to the anticoagulant enocoumarol (PMID:12010835)
• the pharmacokinetics of racemic and of S-ibuprofen depended on the CYP2C9 isoleucine359leucine amino acid polymorphism (PMID:12152005)
• Regulation of human CYP2C9 by the constitutive androstane receptor: discovery of a new distal binding site. (PMID:12181452)
• CYP2C9 genotype influences the blood pressure-decreasing response to antihypertensive treatment with irbesartan (PMID:12359989)
• contributes to the biotransformation of E- and Z-doxepin in healthy volunteers (PMID:12360109)
• structure-function relationship of the CYP2C9 promoter and coding regions [review] (PMID:12406644)
• cytochrome P450 CYP2C9 polymorphisms influence acenocoumarol dose requirements and stability of anticoagulation (PMID:12414349)
• 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)
• CYP2C9 substrate specificity and hydroxylation depend on phenylalanine residues (PMID:12464247)
• CYP 2C9 has role in regulation of hyperaemia and oxygen uptake during exercise. Interaction between CYP 2C9 and NOS appears to exist so that a CYP-dependent vasodilator mechanism takes over when NO production is compromised. (PMID:12509498)
• the presence of N-hydroxydapsone caused the same effects on stoichiometry as those of flurbiprofen 4(’)-hydroxylation but failed to reduce excess water formation, which suggests that, while N-hydroxydapsone activates CYP2C9, it does so less efficiently (PMID:12559973)
• an examination of the promoter sequence (PMID:12668916)
• crystal structure of a human CYP450, CYP2C9, both unliganded and in complex with the anti-coagulant drug warfarin (PMID:12861225)
• pharmacokinetics of both enantiomers of fluvastatin depended on the CYP2C9 genotype, but differences in plasma concentrations were not reflected in cholesterol lowering (PMID:12891229)
• CYP2C9 and CYP2C19 provided enhanced formation of R-EDDP from methadone and CYP2D6 incubation resulted in the preferential conversion to S-EDDP. (PMID:12900870)
• The prevalence of mutations of allelic variant predict genotype frequency in the croatian populations. (PMID:12950145)
• Study shows a higher frequency of the CYP2C9*3 allele in major depressive patients compared to schizophrenic patients and healthy volunteers. (PMID:14583800)
• role of polymorphism of cytochrome P450 CYP2C9 as an independent risk factor modulating the sensitivity of patients to the anticoagulant effect of acenocoumarol (PMID:14614357)
• The ontogeny of CYP2C9 and -2C19 were dissimilar among both fetal and 0- to 5-months postnatal samples, implying different developmental regulatory mechanisms. (PMID:14634042)
• Genotyping of CYP2C9 and certain vitamin K-dependent protein genes is useful for predicting anticoagulant (warfarin) responses. (PMID:14656880)
• review of genetic variants associated with the metabolism of (S)-warfarin by cytochrome P450 2C9, and implications for increased propensity for bleeding (PMID:14739630)
• analysis of the -2.1-kb 5’-flanking region of CYP2C9 was undertaken in 22 white and 38 Japanese patients whose unbound oral clearance of S-warfarin had been previously determined (PMID:15070684)
• “Genetic polymorphism of cytochrome P450 (CYP)enzymes are one of the factors that contribute to the pharmacokinetic variability of drugs.” (PMID:15102864)
• CYP2C9,the most abundant among human CYP2c, metabolises a number of therapeutically important drugs, including most steroidal anti-inflammatory drugs,S-warfarin, phenytoin and losartan" (PMID:15177309)
• Possession of the CYP2C9*2 or CYP2C9*3 variant alleles results in decreased enzyme activity and has been associated with a significant decrease in mean warfarin dose requirements. (PMID:15199455)
• Novel CYP2C9 alleles correlated with reduced plasma clearance of drugs that are substrates for CYP2C9. (PMID:15226678)
• “The results of the present study show that CYP2C9 is not likely to be involved in risperidone metabolism.” P. 191 (PMID:15260906)
• Of several human P450 enzymes, CYP2C9 had the greatest activity for hydroxylation of R-etodolac. (PMID:15370961)
• The frequency of the CYP2C9*2 polymorphism is lower among Mexican-Americans compared to Spaniards (P<0.05). (PMID:15452553)
• Overexpression of CYP2C9 in endothelial cells increased cAMP levels, stimulated the cAMP-response element-binding protein, and enhanced COX-2 promoter activity, protein expression, prostacyclin production, & endothelial tube formation. (PMID:15569819)
• The coding region polymorphisms associated with the CYP2C9 alleles are the major CYP2C9-related factor affecting warfarin dose in UK Caucasians. Upstream CYP2C9 polymorphisms appear not to be important independent determinants of dose requirement. (PMID:15608560)
• The frequency of CYP2C9 genetic variants in the Russian population and their associations with individual sensitivity to warfarin therapy were studied. (PMID:15617742)

Cross-species orthologs

0 orthologs

Paralogs (15): CYP2W1 (ENSG00000073067), CYP2D6 (ENSG00000100197), CYP2C18 (ENSG00000108242), CYP2E1 (ENSG00000130649), CYP2J2 (ENSG00000134716), CYP2C8 (ENSG00000138115), CYP2U1 (ENSG00000155016), CYP2C19 (ENSG00000165841), CYP2S1 (ENSG00000167600), CYP2R1 (ENSG00000186104), CYP2B6 (ENSG00000197408), CYP2F1 (ENSG00000197446), CYP2A13 (ENSG00000197838), CYP2A7 (ENSG00000198077), CYP2A6 (ENSG00000255974)

Protein

Protein identifiers

Cytochrome P450 2C9 — P11712 (reviewed: P11712)

Alternative names: (R)-limonene 6-monooxygenase, (S)-limonene 6-monooxygenase, (S)-limonene 7-monooxygenase, CYPIIC9, Cholesterol 25-hydroxylase, Cytochrome P-450MP, Cytochrome P450 MP-4, Cytochrome P450 MP-8, Cytochrome P450 PB-1, S-mephenytoin 4-hydroxylase

All UniProt accessions (3): P11712, A0A2R8YF67, S5RV20

UniProt curated annotations — full annotation on UniProt →

Function. A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids and steroids. 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). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis. Exhibits low catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2. Catalyzes bisallylic hydroxylation and hydroxylation with double-bond migration of polyunsaturated fatty acids (PUFA). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol. Contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.

Subcellular location. Endoplasmic reticulum membrane. Microsome membrane.

Induction. By rifampicin.

Pathway. Lipid metabolism; arachidonate metabolism. Steroid metabolism; cholesterol metabolism. Terpene metabolism; (4R)-limonene degradation.

Similarity. Belongs to the cytochrome P450 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P11712-1	1	yes
P11712-2	2

RefSeq proteins (1): NP_000762* (*=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 1.14.99.38 — cholesterol 25-monooxygenase (BRENDA: 12 organisms, 12 substrates, 2 inhibitors, 0 Km, 0 kcat entries)

Catalyzed reactions (Rhea), 12 shown:

• an organic molecule + reduced [NADPH–hemoprotein reductase] + O2 = an alcohol + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:17149)
• (4S)-limonene + reduced [NADPH–hemoprotein reductase] + O2 = (1S,5R)-carveol + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:17945)
• (4R)-limonene + reduced [NADPH–hemoprotein reductase] + O2 = (1R,5S)-carveol + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:18957)
• (4S)-limonene + reduced [NADPH–hemoprotein reductase] + O2 = (4S)-perillyl alcohol + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:23432)
• (5Z,8Z,11Z,14Z)-eicosatetraenoate + reduced [NADPH–hemoprotein reductase] + O2 = 19-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:39759)
• (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)
• estrone + reduced [NADPH–hemoprotein reductase] + O2 = 2-hydroxyestrone + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:47208)
• 17beta-estradiol + reduced [NADPH–hemoprotein reductase] + O2 = 2-hydroxy-17beta-estradiol + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:47212)
• (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)

UniProt features (70 total): helix 21, sequence variant 17, strand 17, turn 6, sequence conflict 5, splice variant 2, chain 1, binding site 1

Structure

Experimental structures (PDB)

15 structures.

PDB	Method	Resolution (Å)
1R9O	X-RAY DIFFRACTION	2
5A5I	X-RAY DIFFRACTION	2
5X23	X-RAY DIFFRACTION	2
5W0C	X-RAY DIFFRACTION	2
7RL2	X-RAY DIFFRACTION	2.23
5K7K	X-RAY DIFFRACTION	2.3
5XXI	X-RAY DIFFRACTION	2.3
4NZ2	X-RAY DIFFRACTION	2.45
5X24	X-RAY DIFFRACTION	2.48
8VZ7	X-RAY DIFFRACTION	2.53
1OG5	X-RAY DIFFRACTION	2.55
1OG2	X-RAY DIFFRACTION	2.6
5A5J	X-RAY DIFFRACTION	2.9
8VX0	X-RAY DIFFRACTION	3.05
6VLT	X-RAY DIFFRACTION	3.12

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P11712-F1	93.03	0.79

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 (1): 435 (axial binding residue)

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: 144 (showing top): MORF_RAGE, REACTOME_BIOLOGICAL_OXIDATIONS, WANG_CLIM2_TARGETS_UP, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, GNF2_GSTM1, XU_HGF_TARGETS_REPRESSED_BY_AKT1_DN, GNF2_HPN, GOBP_OXIDATIVE_DEMETHYLATION, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_LONG_CHAIN_FATTY_ACID_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_DEMETHYLATION, CAIRO_HEPATOBLASTOMA_CLASSES_DN, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS

GO Biological Process (17): xenobiotic metabolic process (GO:0006805), steroid metabolic process (GO:0008202), cholesterol metabolic process (GO:0008203), estrogen metabolic process (GO:0008210), monoterpenoid metabolic process (GO:0016098), epoxygenase P450 pathway (GO:0019373), urea metabolic process (GO:0019627), monocarboxylic acid metabolic process (GO:0032787), xenobiotic catabolic process (GO:0042178), long-chain fatty acid biosynthetic process (GO:0042759), icosanoid biosynthetic process (GO:0046456), oxidative demethylation (GO:0070989), organofluorine metabolic process (GO:0090346), omega-hydroxylase P450 pathway (GO:0097267), lipid metabolic process (GO:0006629), terpenoid metabolic process (GO:0006721), arachidonate metabolic process (GO:0019369)

GO Molecular Function (16): monooxygenase activity (GO:0004497), iron ion binding (GO:0005506), arachidonate epoxygenase activity (GO:0008392), steroid hydroxylase activity (GO:0008395), arachidonate 14,15-epoxygenase activity (GO:0008404), arachidonate 11,12-epoxygenase activity (GO:0008405), oxidoreductase activity (GO:0016491), 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), (S)-limonene 6-monooxygenase activity (GO:0018675), (S)-limonene 7-monooxygenase activity (GO:0018676), heme binding (GO:0020037), caffeine oxidase activity (GO:0034875), (R)-limonene 6-monooxygenase activity (GO:0052741), estrogen 2-hydroxylase activity (GO:0101021), oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen (GO:0016705), metal ion binding (GO:0046872)

GO Cellular Component (6): cytoplasm (GO:0005737), endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), intracellular membrane-bounded organelle (GO:0043231), 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
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	4
limonene monooxygenase activity	3
arachidonate metabolic process	2
long-chain fatty acid metabolic process	2
icosanoid metabolic process	2
oxidoreductase activity	2
monooxygenase activity	2
arachidonate epoxygenase activity	2
intracellular anatomical structure	2
cellular anatomical structure	2
metabolic process	1
cellular response to xenobiotic stimulus	1
lipid metabolic process	1
sterol metabolic process	1
secondary alcohol metabolic process	1
steroid metabolic process	1
hormone metabolic process	1
terpenoid metabolic process	1
small molecule metabolic process	1
nitrogen cycle metabolic process	1
carboxylic acid metabolic process	1
xenobiotic metabolic process	1
catabolic process	1
fatty acid biosynthetic process	1
carboxylic acid biosynthetic process	1
demethylation	1
organohalogen metabolic process	1
primary metabolic process	1
isoprenoid metabolic process	1
unsaturated fatty acid metabolic process	1
olefinic compound metabolic process	1
transition metal ion binding	1
arachidonate monooxygenase activity	1
catalytic activity	1
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	1
tetrapyrrole binding	1
oxidoreductase activity, acting on CH or CH2 groups, quinone or similar compound as acceptor	1
steroid hydroxylase activity	1
cation binding	1
organelle membrane	1

Protein interactions and networks

STRING

2122 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CYP2C9	VKORC1	Q9BQB6	980
CYP2C9	PPIG	Q13427	956
CYP2C9	SLCO1B1	Q9Y6L6	911
CYP2C9	GGCX	P38435	905
CYP2C9	UGT1A6	P19224	884
CYP2C9	NR1I2	O75469	833
CYP2C9	UGT1A4	P22310	803
CYP2C9	UGT1A10	Q9HAW8	790
CYP2C9	UGT1A1	P22309	789
CYP2C9	UGT1A8	Q9HAW9	789
CYP2C9	UGT1A7	Q9HAW7	786
CYP2C9	UGT2B4	P06133	783
CYP2C9	UGT2B7	P16662	778
CYP2C9	SLC35A2	P78381	767
CYP2C9	SULT1A1	P50225	742

IntAct

17 interactions, top by confidence:

A	B	Type	Score
CYP2C9	TOMM40	psi-mi:“MI:0914”(association)	0.530
CYP2C18	CYP2C9	psi-mi:“MI:0914”(association)	0.530
CYP2C9	CYP2C19	psi-mi:“MI:0914”(association)	0.530
	CYP2C9	psi-mi:“MI:0407”(direct interaction)	0.440
CYP2C9	CDC37	psi-mi:“MI:0915”(physical association)	0.370
CYP2C9	MAST1	psi-mi:“MI:0915”(physical association)	0.370
CYP2C9	RAB3D	psi-mi:“MI:0915”(physical association)	0.370
RNF32	CYP2C9	psi-mi:“MI:0915”(physical association)	0.370
STAMBP	CYP2C9	psi-mi:“MI:0915”(physical association)	0.370
STAT5A	CYP2C9	psi-mi:“MI:0915”(physical association)	0.370
CYP2C18	PGRMC1	psi-mi:“MI:0914”(association)	0.350

BioGRID (111): CYP2C9 (Affinity Capture-MS), CYP3A4 (Reconstituted Complex), CYP2C9 (Affinity Capture-MS), CYP2C19 (Affinity Capture-MS), CD97 (Affinity Capture-MS), TOMM40 (Affinity Capture-MS), SSR3 (Proximity Label-MS), HNRNPA1L2 (Proximity Label-MS), CYP2C9 (Positive Genetic), ACSL3 (Proximity Label-MS), ADCY9 (Proximity Label-MS), ALDH3A2 (Proximity Label-MS), ANKLE2 (Proximity Label-MS), ARFGAP3 (Proximity Label-MS), CAMLG (Proximity Label-MS)

ESM2 similar proteins: E9Q5K4, O55071, O62671, P00179, P00180, P00181, P00182, P05178, P05179, P05180, P05181, P08683, P11371, P11509, P11711, P11712, P12790, P13107, P15123, P15392, P17666, P19225, P20678, P20812, P20814, P20852, P20853, P24454, P24470, P33260, P33261, P33263, P33264, P33265, P33272, P33273, P56593, P56594, P56654, P56655

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

2 interactions.

A	Effect	B	Mechanism
apigenin	down-regulates	CYP2C9	“chemical inhibition”
baicalein	down-regulates	CYP2C9	“chemical inhibition”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	34
Likely benign	3
Benign	3

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
8410	NM_000771.4(CYP2C9):c.622T>G (p.Leu208Val)	Pathogenic

SpliceAI

1179 predictions. Top by Δscore:

Variant	Effect	Δscore
10:94941856:A:AG	acceptor_gain	1.0000
10:94941857:G:GG	acceptor_gain	1.0000
10:94942019:TG:T	donor_loss	1.0000
10:94942020:GG:G	donor_loss	1.0000
10:94942021:G:GG	donor_gain	1.0000
10:94942022:T:G	donor_loss	1.0000
10:94942191:GGA:G	acceptor_gain	1.0000
10:94942302:G:GT	donor_gain	1.0000
10:94942323:GAGT:G	donor_gain	1.0000
10:94942326:T:G	donor_gain	1.0000
10:94942340:GG:G	donor_gain	1.0000
10:94942341:GG:G	donor_gain	1.0000
10:94947935:TCCAG:T	donor_loss	1.0000
10:94947937:CAGGT:C	donor_loss	1.0000
10:94947938:AGGT:A	donor_loss	1.0000
10:94947939:GGT:G	donor_loss	1.0000
10:94947941:T:A	donor_loss	1.0000
10:94972240:TCAC:T	donor_gain	1.0000
10:94972241:CACAG:C	donor_loss	1.0000
10:94972242:ACAGG:A	donor_loss	1.0000
10:94972244:AG:A	donor_loss	1.0000
10:94972245:GG:G	donor_loss	1.0000
10:94972247:T:G	donor_loss	1.0000
10:94938815:A:G	donor_gain	0.9900
10:94938851:G:GG	donor_gain	0.9900
10:94941848:A:AG	acceptor_gain	0.9900
10:94941849:C:G	acceptor_gain	0.9900
10:94941856:A:G	acceptor_loss	0.9900
10:94941857:GC:G	acceptor_gain	0.9900
10:94941857:GCT:G	acceptor_gain	0.9900

AlphaMissense

3257 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:94986165:T:C	F428L	0.985
10:94986167:C:A	F428L	0.985
10:94986167:C:G	F428L	0.985
10:94981269:G:C	A350P	0.981
10:94986117:T:C	F412L	0.981
10:94986119:T:A	F412L	0.981
10:94986119:T:G	F412L	0.981
10:94986084:T:C	F401L	0.978
10:94986086:T:A	F401L	0.978
10:94986086:T:G	F401L	0.978
10:94981292:A:C	R357S	0.971
10:94981292:A:T	R357S	0.971
10:94942305:G:C	A149P	0.969
10:94941913:T:A	V75E	0.965
10:94988891:T:C	F446L	0.965
10:94988893:T:A	F446L	0.965
10:94988893:T:G	F446L	0.965
10:94941980:A:C	R97S	0.963
10:94941980:A:T	R97S	0.963
10:94981291:G:C	R357T	0.963
10:94938805:T:A	N41K	0.961
10:94938805:T:G	N41K	0.961
10:94988921:T:C	F456L	0.961
10:94988923:T:A	F456L	0.961
10:94988923:T:G	F456L	0.961
10:94942236:T:C	F126L	0.959
10:94942238:C:A	F126L	0.959
10:94942238:C:G	F126L	0.959
10:94942255:G:C	R132P	0.959
10:94942231:G:C	R124P	0.957

dbSNP variants (sampled 300 via entrez): RS1000001742 (10:94957369 CT>C,CTT), RS1000080177 (10:94939055 C>A), RS1000110511 (10:94978013 C>A,T), RS1000154154 (10:94953418 C>A), RS1000193052 (10:94962448 G>A), RS1000231367 (10:94961746 A>G), RS1000279424 (10:94987525 G>A), RS1000303460 (10:94958010 T>A,G), RS1000354392 (10:94967499 T>C), RS1000441562 (10:94977685 C>G), RS1000460185 (10:94962154 G>T), RS1000466565 (10:94943798 G>T), RS1000538930 (10:94981804 C>G,T), RS1000568662 (10:94960645 C>A,T), RS1000572833 (10:94947513 C>T)

Disease associations

OMIM: gene MIM:601130 | disease phenotypes: MIM:122700

GenCC curated gene-disease

Mondo (2): pulmonary disease, chronic obstructive, susceptibility to (MONDO:0100167), coumarin resistance (MONDO:0007390)

Orphanet (0):

HPO phenotypes

2 total (2 of 2 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001871	Abnormality of blood and blood-forming tissues

GWAS associations

20 associations (top):

Study	Trait	p-value
GCST000204_2	Warfarin maintenance dose	6.000000e-12
GCST000360_2	Warfarin maintenance dose	1.000000e-31
GCST000360_4	Warfarin maintenance dose	3.000000e-79
GCST000467_1	Response to clopidogrel therapy	2.000000e-13
GCST000792_5	Warfarin maintenance dose	4.000000e-07
GCST001038_3	Dehydroepiandrosterone sulphate levels	2.000000e-08
GCST001491_37	Immune response to smallpox vaccine (IL-6)	2.000000e-07
GCST002061_1	Warfarin maintenance dose	5.000000e-12
GCST002549_1	Response to serotonin reuptake inhibitors in major depressive disorder (plasma drug and metabolite levels)	2.000000e-16
GCST002549_2	Response to serotonin reuptake inhibitors in major depressive disorder (plasma drug and metabolite levels)	4.000000e-09
GCST003085_9	Warfarin maintenance dose	2.000000e-13
GCST004264_1	Clopidogrel active metabolite levels	1.000000e-14
GCST004266_1	Response to clopidogrel therapy	1.000000e-16
GCST006249_39	Serum metabolite levels	7.000000e-23
GCST006249_40	Serum metabolite levels	7.000000e-21
GCST007094_20	Diastolic blood pressure	2.000000e-06
GCST007096_250	Pulse pressure	2.000000e-06
GCST007099_101	Systolic blood pressure	1.000000e-09
GCST007684_2	Plasma clozapine-norclozapine ratio in treatment-resistant schizophrenia	5.000000e-14
GCST011998_7	Glucocorticoid receptor gene expression in B-cell precursor acute lymphoblastic leukaemia	3.000000e-06

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004730	hormone measurement
EFO:0004645	response to vaccine
EFO:0005658	response to selective serotonin reuptake inhibitor
EFO:0007966	clopidogrel metabolite measurement
EFO:0006336	diastolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0006335	systolic blood pressure
EFO:0600040	plasma clozapine-to-N-desmethylclozapine ratio measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C563039	Coumarin Resistance (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3397 (SINGLE PROTEIN), CHEMBL4523986 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

357 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 866,446 (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
CHEMBL1008	BEPRIDIL	4	11,776
CHEMBL101	PHENYLBUTAZONE	4	59,455
CHEMBL1017	TELMISARTAN	4	27,457
CHEMBL1018	DIENESTROL	4	5,607
CHEMBL103	PROGESTERONE	4	162,141
CHEMBL1034	DICLOFENAC SODIUM	4	45,460
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL1043	DAPSONE	4	64,779
CHEMBL106	FLUCONAZOLE	4	58,942
CHEMBL107	COLCHICINE	4	93,932
CHEMBL1073	GLIPIZIDE	4	42,268
CHEMBL1089	PHENELZINE	4	18,793
CHEMBL1108	DROPERIDOL	4	16,888
CHEMBL1109	SULFAPHENAZOLE	4	4,065
CHEMBL111	RIMONABANT	4	15,726
CHEMBL1123	DICYCLOMINE	4	8,691
CHEMBL1148	TORSEMIDE	4	15,151
CHEMBL1170	TESTOSTERONE PROPIONATE	4	17,619
CHEMBL1175	DULOXETINE	4	28,527
CHEMBL118	CELECOXIB	4	112,844
CHEMBL1200326	NICARDIPINE HYDROCHLORIDE	4
CHEMBL1200604	TROPICAMIDE	4
CHEMBL1200681	MONTELUKAST SODIUM	4
CHEMBL1200806	NAPROXEN SODIUM	4
CHEMBL1201039	BENZTHIAZIDE	4
CHEMBL1201139	MEGESTROL ACETATE	4
CHEMBL1201155	LOXAPINE SUCCINATE	4
CHEMBL1201217	DYCLONINE	4
CHEMBL1201322	THONZONIUM	4
CHEMBL1221	SULCONAZOLE	4

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

PharmGKB clinical annotations

74 annotations.

Variant	Type	Level	Drugs	Phenotypes
CYP2C91, CYP2C919, CYP2C927, CYP2C936, CYP2C940, CYP2C941, CYP2C947, CYP2C949, CYP2C951, CYP2C953, CYP2C954, CYP2C956	Metabolism/PK	3	phenytoin
CYP2C91, CYP2C929	Metabolism/PK	3	warfarin
CYP2C91, CYP2C92	Toxicity	3	ketoprofen	Dyspepsia;Pain;Postoperative
CYP2C91, CYP2C92, CYP2C9*3	Metabolism/PK	1A	ibuprofen
CYP2C91, CYP2C92, CYP2C9*3	Toxicity	2A	acenocoumarol	Hemorrhage
CYP2C91, CYP2C92, CYP2C9*3	Dosage,Metabolism/PK	3	valproic acid	Bipolar Disorder;Psychotic Disorder
CYP2C91, CYP2C92, CYP2C9*3	Toxicity	3	sulfonamides;urea derivatives	Diabetes Mellitus;Type 2
CYP2C91, CYP2C92, CYP2C9*3	Efficacy	3	sulfonamides;urea derivatives	Diabetes Mellitus
CYP2C91, CYP2C92, CYP2C9*3	Dosage	3	phenprocoumon
CYP2C91, CYP2C92, CYP2C9*3	Metabolism/PK	3	phenprocoumon
CYP2C91, CYP2C92, CYP2C9*3	Efficacy	3	ketorolac	Pain;Postoperative
CYP2C91, CYP2C92, CYP2C9*3	Metabolism/PK	4	methadone
CYP2C91, CYP2C92, CYP2C9*3	Efficacy	4	clopidogrel	Acute coronary syndrome;Coronary Artery Disease
CYP2C91, CYP2C92, CYP2C9*3	Efficacy	4	warfarin
CYP2C91, CYP2C92, CYP2C9*3	Metabolism/PK	1A	tenoxicam
CYP2C91, CYP2C92, CYP2C9*3	Metabolism/PK	1A	piroxicam
CYP2C91, CYP2C92, CYP2C9*3	Toxicity	1A	phenytoin	Epilepsy
CYP2C91, CYP2C92, CYP2C9*3	Metabolism/PK	1A	fluvastatin
CYP2C91, CYP2C92, CYP2C9*3	Toxicity	1A	fluvastatin
CYP2C91, CYP2C92, CYP2C9*3	Metabolism/PK	1A	siponimod
CYP2C91, CYP2C92, CYP2C9*3	Toxicity	1B	acenocoumarol	over-anticoagulation
CYP2C91, CYP2C92, CYP2C9*3	Dosage	1B	acenocoumarol
CYP2C91, CYP2C92, CYP2C93, CYP2C913	Metabolism/PK	1A	celecoxib
CYP2C91, CYP2C92, CYP2C93, CYP2C913	Metabolism/PK	1A	meloxicam
CYP2C91, CYP2C92, CYP2C93, CYP2C913, CYP2C9*14	Efficacy	2A	warfarin	Atrial Fibrillation;Heart valve replacement
CYP2C91, CYP2C92, CYP2C93, CYP2C929	Metabolism/PK	1A	flurbiprofen
CYP2C91, CYP2C92, CYP2C93, CYP2C929	Metabolism/PK	4	naproxen
CYP2C91, CYP2C92, CYP2C93, CYP2C94, CYP2C95, CYP2C96, CYP2C98, CYP2C911	Dosage	1A	warfarin	Cardiovascular Disease
CYP2C91, CYP2C92, CYP2C93, CYP2C95, CYP2C96, CYP2C911	Toxicity	1A	warfarin	over-anticoagulation
CYP2C91, CYP2C92, CYP2C93, CYP2C95, CYP2C96, CYP2C911	Toxicity	1A	warfarin	Hemorrhage
CYP2C91, CYP2C92, CYP2C93, CYP2C95, CYP2C96, CYP2C98, CYP2C911, CYP2C913, CYP2C914, CYP2C916, CYP2C929, CYP2C931, CYP2C933, CYP2C937, CYP2C939, CYP2C942, CYP2C943, CYP2C945, CYP2C950, CYP2C952, CYP2C9*55	Metabolism/PK	1A	phenytoin	Epilepsy
CYP2C91, CYP2C92, CYP2C93, CYP2C95, CYP2C96, CYP2C98, CYP2C913, CYP2C959, CYP2C9*62	Metabolism/PK	3	losartan
CYP2C91, CYP2C92, CYP2C93, CYP2C962	Metabolism/PK	3	tolbutamide
CYP2C91, CYP2C92, CYP2C93, CYP2C96	Toxicity	3	olanzapine	Hypotensive disorder
CYP2C91, CYP2C92, CYP2C93, CYP2C98, CYP2C913, CYP2C936, CYP2C937, CYP2C938, CYP2C939, CYP2C940, CYP2C942, CYP2C943, CYP2C944, CYP2C945, CYP2C946, CYP2C947, CYP2C948, CYP2C950, CYP2C952, CYP2C953, CYP2C954, CYP2C955, CYP2C959, CYP2C960, CYP2C9*62	Metabolism/PK	3	diclofenac
CYP2C91, CYP2C93	Efficacy	3	doxepin
CYP2C91, CYP2C93	Other	3	trimipramine
CYP2C91, CYP2C93	Metabolism/PK	3	dipyrone
CYP2C91, CYP2C93	Toxicity	3	indomethacin

PharmGKB variants

106 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1057910	CYP2C9	3	6.00	44	Antiinflammatory agents;non-steroids;celecoxib;diclofenac;losartan;irbesartan
rs1057911	CYP2C9		0.00	0
rs1799853	CYP2C9	3	3.00	37	busulfan;hormonal contraceptives for systemic use;irbesartan
rs1934969	CYP2C9	3	2.75	2	losartan;phenytoin
rs2256871	CYP2C9		0.00	0
rs2860905	CYP2C9		0.00	0
rs4086116	CYP2C9	3	2.50	2	acenocoumarol;phenprocoumon
rs4917639	CYP2C9	3	5.50	1	warfarin
rs4918758	CYP2C9	3	2.75	1	warfarin
rs7089580	CYP2C9	3	5.75	1	warfarin
rs7900194	CYP2C9		0.00	5
rs9332094	CYP2C9		0.00	0
rs9332096	CYP2C9	3	3.50	2	warfarin;ethambutol;isoniazid;pyrazinamide;rifampin
rs9332104	CYP2C9		0.00	0
rs9332120	CYP2C9		0.00	0
rs9332127	CYP2C9		0.00	0
rs9332130	CYP2C9		0.00	0
rs9332131	CYP2C9		0.00	6
rs9332174	CYP2C9		0.00	0
rs9332197	CYP2C9		0.00	0
rs9332238	CYP2C9		0.00	0
rs9332239	CYP2C9	3	0.00	1	tolbutamide
rs10509680	CYP2C9	3	3.00	1	warfarin
rs12414460	CYP2C9		0.00	2
rs12782374	CYP2C9	3	2.00	1	phenytoin
rs28371685	CYP2C9		0.00	4
rs28371686	CYP2C9		0.00	7
rs56165452	CYP2C9		0.00	1
rs57505750	CYP2C9		0.00	1
rs71486745	CYP2C9	3	2.00	1	phenytoin
rs72558187	CYP2C9	3	4.50	9	irbesartan
rs72558189	CYP2C9		0.00	2
rs72558192	CYP2C9		0.00	1
rs114071557	CYP2C9		0.00	2
rs141011391	CYP2C9		0.00	0
rs142240658	CYP2C9		0.00	0
rs182132442	CYP2C9		0.00	4
rs199523631	CYP2C9		0.00	2
rs200965026	CYP2C9		0.00	1
rs367826293	CYP2C9		0.00	0

PharmGKB dosing guidelines

19 guidelines.

Source	Drug	Guideline	Dosing?	Recommendation?
CPIC	aceclofenac;aspirin;diclofenac;dipyrone;indomethacin;lumiracoxib;nabumetone;naproxen	Annotation of CPIC Guideline for aceclofenac, aspirin, diclofenac, dipyrone, indomethacin, lumiracoxib, nabumetone, naproxen and CYP2C9
CPIC	celecoxib;flurbiprofen;ibuprofen;lornoxicam	Annotation of CPIC Guideline for celecoxib, flurbiprofen, ibuprofen, lornoxicam and CYP2C9	yes	yes
CPIC	fluvastatin	Annotation of CPIC Guideline for fluvastatin and CYP2C9, SLCO1B1	yes	yes
CPIC	fosphenytoin;phenytoin	Annotation of CPIC Guideline for fosphenytoin, phenytoin and CYP2C9, HLA-B	yes	yes
CPIC	meloxicam	Annotation of CPIC Guideline for meloxicam and CYP2C9	yes	yes
CPIC	piroxicam	Annotation of CPIC Guideline for piroxicam and CYP2C9		yes
CPIC	tenoxicam	Annotation of CPIC Guideline for tenoxicam and CYP2C9		yes
CPIC	warfarin	Annotation of CPIC Guideline for warfarin and CYP2C9, CYP4F2, VKORC1	yes	yes
DPWG	acenocoumarol	Annotation of DPWG Guideline for acenocoumarol and CYP2C9
DPWG	gliclazide	Annotation of DPWG Guideline for gliclazide and CYP2C9
DPWG	glimepiride	Annotation of DPWG Guideline for glimepiride and CYP2C9
DPWG	glyburide	Annotation of DPWG Guideline for glyburide and CYP2C9
DPWG	phenprocoumon	Annotation of DPWG Guideline for phenprocoumon and CYP2C9
DPWG	phenytoin	Annotation of DPWG Guideline for phenytoin and CYP2C9	yes	yes
DPWG	siponimod	Annotation of DPWG Guideline for siponimod and CYP2C9	yes	yes
DPWG	tolbutamide	Annotation of DPWG Guideline for tolbutamide and CYP2C9
DPWG	warfarin	Annotation of DPWG Guideline for warfarin and CYP2C9	yes	yes
CPNDS	warfarin	Annotation of CPNDS Guideline for warfarin and CYP2C9, VKORC1	yes	yes
RNPGx	acenocoumarol;fluindione;warfarin	Annotation of RNPGx Guideline for acenocoumarol, fluindione, warfarin and CYP2C9, VKORC1	yes	yes

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — CYP2 family: drug metabolising subset

Most potent curated ligand interactions (4 total), top 4:

Ligand	Action	Affinity	Parameter
compound 3 [PMID: 18255300]	Inhibition	8.38	pKi
compound 51 [Crosignani et al., 2011]	Inhibition	6.7	pIC50
sulfaphenazole	Inhibition	6.52	pKi
voxelotor	Inhibition	5.07	pIC50

Binding affinities (BindingDB)

198 measured of 460 human assays (460 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(6S)-6-(4-fluorophenyl)-3-[(1S)-1-[4-(4-fluorophenyl)phenyl]ethyl]-6-(2-hydroxyethyl)-1,3-oxazinan-2-one	IC50	0.51 nM	US-8598163: Derivatives of [1,3]Oxazin-2-one useful for the treatment of metabolic diseases such as lipid disorders
3-[(6R)-3-[(1S)-1-[4-(4-fluorophenyl)phenyl]ethyl]-2-oxo-6-phenyl-1,3-oxazinan-6-yl]propanamide	IC50	0.55 nM	US-8598163: Derivatives of [1,3]Oxazin-2-one useful for the treatment of metabolic diseases such as lipid disorders
(6R)-3-[(1S)-1-[4-(4-fluorophenyl)phenyl]ethyl]-6-(3-hydroxypropyl)-6-phenyl-1,3-oxazinan-2-one	IC50	0.55 nM	US-8598163: Derivatives of [1,3]Oxazin-2-one useful for the treatment of metabolic diseases such as lipid disorders
2,2-dimethyl-3-[(6R)-3-[(1S)-1-[4-(1-methyl-2-oxo-4-pyridinyl)phenyl]ethyl]-2-oxo-6-phenyl-1,3-oxazinan-6-yl]propanenitrile	IC50	0.61 nM	US-8575157
(6R)-6-(2,2-dimethylbut-3-ynyl)-3-[(1S)-1-[4-(6-oxo-1H-pyridin-3-yl)phenyl]ethyl]-6-phenyl-1,3-oxazinan-2-one	IC50	0.65 nM	US-8575157
3-[(6R)-6-(4-fluorophenyl)-3-[(1S)-1-[4-(1-methyl-6-oxo-3-pyridinyl)phenyl]ethyl]-2-oxo-1,3-oxazinan-6-yl]-2,2-dimethylpropanenitrile	IC50	0.72 nM	US-8575157
(6R)-3-[(1S)-1-[4-(2,4-difluorophenyl)phenyl]ethyl]-6-(3-hydroxypropyl)-6-phenyl-1,3-oxazinan-2-one	IC50	0.72 nM	US-8598163: Derivatives of [1,3]Oxazin-2-one useful for the treatment of metabolic diseases such as lipid disorders
(6S)-3-[(1S)-1-[4-(2,4-difluorophenyl)phenyl]ethyl]-6-(4-fluorophenyl)-6-(2-hydroxyethyl)-1,3-oxazinan-2-one	IC50	0.75 nM	US-8598163: Derivatives of [1,3]Oxazin-2-one useful for the treatment of metabolic diseases such as lipid disorders
(6S)-3-[(1S)-1-(4-bromophenyl)ethyl]-6-(4-fluorophenyl)-6-(2-hydroxy-2-methylpropyl)-1,3-oxazinan-2-one	IC50	0.76 nM	US-8598163: Derivatives of [1,3]Oxazin-2-one useful for the treatment of metabolic diseases such as lipid disorders
(6S)-3-[3-(2,4-difluorophenyl)phenyl]-6-(2-hydroxyethyl)-6-phenyl-1,3-oxazinan-2-one	IC50	0.77 nM	US-8598163: Derivatives of [1,3]Oxazin-2-one useful for the treatment of metabolic diseases such as lipid disorders
(6S)-3-[(1S)-1-(4-bromophenyl)ethyl]-6-(2-hydroxy-2-methylpropyl)-6-phenyl-1,3-oxazinan-2-one	IC50	0.79 nM	US-8598163: Derivatives of [1,3]Oxazin-2-one useful for the treatment of metabolic diseases such as lipid disorders
(6S)-3-[(1S)-1-[4-(1-ethyl-2-oxo-4-pyridinyl)phenyl]ethyl]-6-(2-hydroxy-2-methylpropyl)-6-phenyl-1,3-oxazinan-2-one	IC50	0.8 nM	US-8575157
(6S)-3-[(1S)-1-[4-[1-(cyclopropylmethyl)-6-oxopyridazin-3-yl]phenyl]ethyl]-6-(2-hydroxy-2-methylpropyl)-6-phenyl-1,3-oxazinan-2-one	IC50	0.86 nM	US-8592410: Cyclic inhibitors of 11BETA-hydroxysteroid dehydrogenase 1
(6R)-6-ethyl-3-[(1S)-1-[4-(1-methyl-2-oxo-4-pyridinyl)phenyl]propyl]-6-phenyl-1,3-oxazinan-2-one	IC50	0.87 nM	US-8575157
(6S)-6-(2-hydroxy-2-methylpropyl)-3-[(1S)-1-[4-(2-oxo-1-propan-2-yl-4-pyridinyl)phenyl]ethyl]-6-phenyl-1,3-oxazinan-2-one	IC50	0.96 nM	US-8575157
(6R)-6-(3-hydroxypropyl)-3-[(1S)-1-[4-(1-methyl-2-oxo-4-pyridinyl)phenyl]ethyl]-6-phenyl-1,3-oxazinan-2-one	IC50	0.96 nM	US-8575157
3-[(6R)-3-[(1S)-1-[4-(2,4-difluorophenyl)phenyl]ethyl]-6-(4-fluorophenyl)-2-oxo-1,3-oxazinan-6-yl]propanamide	IC50	0.99 nM	US-8598163: Derivatives of [1,3]Oxazin-2-one useful for the treatment of metabolic diseases such as lipid disorders
(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
(6S)-3-[(1S)-1-[4-(1-ethyl-5-methyl-6-oxo-3-pyridinyl)phenyl]ethyl]-6-(2-hydroxy-2-methylpropyl)-6-phenyl-1,3-oxazinan-2-one	IC50	1.01 nM	US-8575157
2,2-dimethyl-3-[(6R)-3-[(1S)-1-[4-(1-methyl-6-oxo-3-pyridinyl)phenyl]ethyl]-2-oxo-6-phenyl-1,3-oxazinan-6-yl]propanenitrile	IC50	1.03 nM	US-8575157
(6S)-3-[(1S)-1-[4-(1-cyclopropyl-6-oxopyridazin-3-yl)phenyl]ethyl]-6-(2-hydroxy-2-methylpropyl)-6-phenyl-1,3-oxazinan-2-one	IC50	1.08 nM	US-8592410: Cyclic inhibitors of 11BETA-hydroxysteroid dehydrogenase 1
(6S)-3-[(1S)-1-[4-(4-fluorophenyl)phenyl]ethyl]-6-(2-hydroxy-2-methylpropyl)-6-phenyl-1,3-oxazinan-2-one	IC50	1.08 nM	US-8598163: Derivatives of [1,3]Oxazin-2-one useful for the treatment of metabolic diseases such as lipid disorders
2,2-dimethyl-3-[(6R)-2-oxo-3-[(1S)-1-[4-(2-oxo-1H-pyridin-4-yl)phenyl]ethyl]-6-phenyl-1,3-oxazinan-6-yl]propanenitrile	IC50	1.11 nM	US-8575157
(6S)-6-(2-hydroxy-2-methylpropyl)-3-[(1S)-1-[4-[6-oxo-1-(2,2,2-trifluoroethyl)pyridazin-3-yl]phenyl]ethyl]-6-phenyl-1,3-oxazinan-2-one	IC50	1.14 nM	US-8592410: Cyclic inhibitors of 11BETA-hydroxysteroid dehydrogenase 1
(6S)-3-[(1S)-1-[4-(1-cyclopropyl-2-oxo-4-pyridinyl)phenyl]ethyl]-6-(2-fluorophenyl)-6-(2-hydroxy-2-methylpropyl)-1,3-oxazinan-2-one	IC50	1.2 nM	US-8575157
(6S)-3-[(1S)-1-[4-(1,5-dimethyl-6-oxopyridazin-3-yl)phenyl]ethyl]-6-(2-hydroxy-2-methylpropyl)-6-phenyl-1,3-oxazinan-2-one	IC50	1.25 nM	US-8592410: Cyclic inhibitors of 11BETA-hydroxysteroid dehydrogenase 1
(6S)-3-[(1S)-1-[4-[1-(difluoromethyl)-2-oxo-4-pyridinyl]phenyl]ethyl]-6-(2-hydroxy-2-methylpropyl)-6-phenyl-1,3-oxazinan-2-one	IC50	1.25 nM	US-8575157
(6S)-3-[(1S)-1-[4-(difluoromethoxy)phenyl]ethyl]-6-(4-fluorophenyl)-6-(2-hydroxyethyl)-1,3-oxazinan-2-one	IC50	1.3 nM	US-8598163: Derivatives of [1,3]Oxazin-2-one useful for the treatment of metabolic diseases such as lipid disorders
(6S)-3-[(1S)-1-[4-(1-ethyl-6-oxo-3-pyridinyl)phenyl]ethyl]-6-(2-hydroxy-2-methylpropyl)-6-phenyl-1,3-oxazinan-2-one	IC50	1.35 nM	US-8575157
(6S)-6-(4-fluorophenyl)-6-(2-hydroxy-2-methylpropyl)-3-[(1S)-1-[4-(1-methyl-6-oxopyridazin-3-yl)phenyl]ethyl]-1,3-oxazinan-2-one	IC50	1.39 nM	US-8592410: Cyclic inhibitors of 11BETA-hydroxysteroid dehydrogenase 1
(6R)-6-(3-hydroxypropyl)-3-[(1S)-1-[4-(6-oxo-1H-pyridin-3-yl)phenyl]ethyl]-6-phenyl-1,3-oxazinan-2-one	IC50	1.39 nM	US-8575157
(6S)-3-[(1S)-1-[4-(1,5-dimethyl-6-oxo-3-pyridinyl)phenyl]ethyl]-6-(2-hydroxy-2-methylpropyl)-6-phenyl-1,3-oxazinan-2-one	IC50	1.4 nM	US-8575157
(6S)-3-[(1S)-1-[4-(1-cyclopropyl-2-oxo-4-pyridinyl)phenyl]ethyl]-6-(2-hydroxy-2-methylpropyl)-6-phenyl-1,3-oxazinan-2-one	IC50	1.4 nM	US-8575157
(6S)-3-[6-(4-fluorophenyl)-2-pyridinyl]-6-(2-hydroxyethyl)-6-phenyl-1,3-oxazinan-2-one	IC50	1.44 nM	US-8598163: Derivatives of [1,3]Oxazin-2-one useful for the treatment of metabolic diseases such as lipid disorders
(6R)-6-(3-hydroxypropyl)-3-[(1S)-1-[4-(1-methyl-6-oxo-3-pyridinyl)phenyl]ethyl]-6-phenyl-1,3-oxazinan-2-one	IC50	1.44 nM	US-8575157
(6S)-6-(2-hydroxy-2-methylpropyl)-3-[(1S)-1-[4-[2-oxo-1-(2,2,2-trifluoroethyl)-4-pyridinyl]phenyl]ethyl]-6-phenyl-1,3-oxazinan-2-one	IC50	1.47 nM	US-8575157
(6S)-3-[(1S)-1-[4-(2,4-difluorophenyl)phenyl]ethyl]-6-(4-fluorophenyl)-6-(2-hydroxy-2-methylpropyl)-1,3-oxazinan-2-one	IC50	1.48 nM	US-8598163: Derivatives of [1,3]Oxazin-2-one useful for the treatment of metabolic diseases such as lipid disorders
(6S)-6-(2-fluorophenyl)-6-(2-hydroxy-2-methylpropyl)-3-[(1S)-1-[4-(1-methyl-2-oxo-4-pyridinyl)phenyl]ethyl]-1,3-oxazinan-2-one	IC50	1.49 nM	US-8575157
(6S)-3-[(1S)-1-[4-(1-ethyl-6-oxopyridazin-3-yl)phenyl]ethyl]-6-(2-hydroxy-2-methylpropyl)-6-phenyl-1,3-oxazinan-2-one	IC50	1.52 nM	US-8592410: Cyclic inhibitors of 11BETA-hydroxysteroid dehydrogenase 1

ChEMBL bioactivities

6100 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.30	IC50	0.5	nM	QUIFLAPON
9.03	IC50	0.93	nM	TARANABANT
9.00	IC50	1	nM	CHEMBL38958
9.00	IC50	1	nM	CHEMBL1825089
8.90	AC50	1.259	nM	KAEMPFEROL
8.89	Potency	1.3	nM	KAEMPFEROL
8.82	IC50	1.5	nM	CHEMBL1922663
8.80	Potency	1.6	nM	CHEMBL1337541
8.80	Potency	1.6	nM	1R,9S-HYDRASTINE
8.80	AC50	1.585	nM	CHEMBL1337541
8.80	AC50	1.585	nM	1R,9S-HYDRASTINE
8.60	Potency	2.5	nM	CHEMBL1513508
8.60	Potency	2.5	nM	CHEMBL1568083
8.60	Potency	2.5	nM	CHEMBL1513940
8.60	Potency	2.5	nM	CHEMBL1517793
8.59	IC50	2.6	nM	CHEMBL1223034
8.57	IC50	2.7	nM	CHEMBL4593464
8.52	IC50	3	nM	CHEMBL1172346
8.49	IC50	3.2	nM	CHEMBL5561914
8.49	Potency	3.2	nM	CHEMBL1355040
8.47	IC50	3.4	nM	CHEMBL4557596
8.40	Potency	4	nM	CHEMBL1452657
8.40	Potency	4	nM	CHEMBL1411360
8.38	Ki	4.2	nM	CHEMBL456432
8.35	IC50	4.5	nM	CHEMBL1229205
8.30	Potency	5	nM	SULFAMERAZINE
8.30	Potency	5	nM	CHEMBL1329823
8.30	Potency	5	nM	CHEMBL1551557
8.30	Potency	5	nM	SULOCTIDIL
8.30	Potency	5	nM	CHEMBL1357770
8.30	AC50	5.012	nM	CHEMBL1595491
8.30	AC50	5.012	nM	CHEMBL1357770
8.30	AC50	5.012	nM	SULOCTIDIL
8.28	IC50	5.3	nM	RIMONABANT
8.25	AC50	5.623	nM	CHEMBL1331572
8.25	AC50	5.623	nM	CHEMBL1717461
8.25	AC50	5.623	nM	CHEMBL1413367
8.25	AC50	5.623	nM	CHEMBL1331020
8.25	AC50	5.623	nM	CHEMBL1703998
8.25	AC50	5.623	nM	CHEMBL1487316
8.25	AC50	5.623	nM	CHEMBL1401073
8.25	AC50	5.623	nM	CHEMBL1571970
8.25	AC50	5.623	nM	CHEMBL1440921
8.25	AC50	5.623	nM	CHEMBL1414071
8.25	AC50	5.623	nM	CHEMBL1419308
8.25	AC50	5.623	nM	CHEMBL3198484
8.25	AC50	5.623	nM	CHEMBL1710203
8.25	AC50	5.623	nM	CHEMBL1531213
8.25	AC50	5.623	nM	CHEMBL1607206
8.25	AC50	5.623	nM	CHEMBL1736619

PubChem BioAssay actives

1034 with measured affinity, of 6100 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
N-[(2S,3S)-4-(4-chlorophenyl)-3-(3-cyanophenyl)butan-2-yl]-2-methyl-2-[[5-(trifluoromethyl)-2-pyridinyl]oxy]propanamide	501824: Inhibition of CYP2C9 in human liver microsomes after 30 mins	ic50	0.0009	uM
5-cyano-N-[2-(cyclohexen-1-yl)-4-pyridin-4-ylphenyl]-1H-imidazole-2-carboxamide	489893: Inhibition of CYP2C9	ic50	0.0030	uM
(1R,2S,5S,8R,9R,10S,11R,18R)-10,18-dihydroxy-12,12-dimethyl-6-methylidene-9-(1,3-thiazol-5-ylmethoxy)-17-oxapentacyclo[7.6.2.15,8.01,11.02,8]octadec-14-en-7-one	2072304: Inhibition of CYP2C9 (unknown origin) using diclofenac as substrate preincubated for 5 min followed by NADPH addition and measured after 15 mins	ic50	0.0032	uM
3-(4-hydroxy-3,5-diiodobenzoyl)-2-propylchromen-4-one	381656: Binding affinity to CYP2C9	ki	0.0042	uM
5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-piperidin-1-ylpyrazole-3-carboxamide	501824: Inhibition of CYP2C9 in human liver microsomes after 30 mins	ic50	0.0053	uM
4-[[4-(benzotriazol-1-yl)pyrimidin-2-yl]amino]cyclohexan-1-ol	769535: Inhibition of CYP2C9 (unknown origin)	ic50	0.0078	uM
6-bromo-N-naphthalen-2-yl-2-pyridin-4-ylquinoline-4-carboxamide	413199: Inhibition of reconstituted CYP2C9	ki	0.0090	uM
3-[3-tert-butylsulfanyl-5-(pyridin-2-ylmethoxy)-1-[[4-(1,3-thiazol-2-yl)phenyl]methyl]indol-2-yl]-2,2-dimethylpropanoic acid	432014: Inhibition of CYP2C9	ic50	0.0091	uM
6,8-dimethyl-N-naphthalen-2-yl-2-pyridin-4-ylquinoline-4-carboxamide	413199: Inhibition of reconstituted CYP2C9	ki	0.0110	uM
6-chloro-N-naphthalen-2-yl-2-pyridin-4-ylquinoline-4-carboxamide	413199: Inhibition of reconstituted CYP2C9	ki	0.0120	uM
3-[3-tert-butylsulfanyl-5-(pyridin-2-ylmethoxy)-1-[(4-pyridin-3-ylphenyl)methyl]indol-2-yl]-2,2-dimethylpropanoic acid	432014: Inhibition of CYP2C9	ic50	0.0155	uM
4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-(6-imidazol-1-yl-4-methyl-1H-benzimidazol-2-yl)-1H-pyridin-2-one	254885: Concentration required to inhibit Cytochrome P450 2C9 in vitro by 50%	ic50	0.0180	uM
(3,5-dibromo-4-hydroxyphenyl)-(2-ethyl-1-benzofuran-3-yl)methanone	282443: Inhibition of human CYP2C9	ki	0.0190	uM
3-[(E)-[3-[(E)-2-pyridin-4-ylethenyl]indazol-6-ylidene]methyl]-1H-indol-2-ol	1178621: Inhibition of CYP2C9 (unknown origin) using MFC substrate after 45 mins by fluorescence assay	ic50	0.0200	uM
(2R,3R)-2-(2,4-difluorophenyl)-3-[3-(2,4-difluorophenyl)prop-2-ynoxy]-1-(1,2,4-triazol-1-yl)butan-2-ol	2131804: Inhibition of human CYP2C9 using diclofenac as substrate prewarmed for 10 mins followed by NADPH addition and measured after 10 mins by LC-MS/MS analysis	ic50	0.0230	uM
3-[3-tert-butylsulfanyl-1-[[4-(6-methoxypyridazin-3-yl)phenyl]methyl]-5-(pyridin-2-ylmethoxy)indol-2-yl]-2,2-dimethylpropanoic acid	432014: Inhibition of CYP2C9	ic50	0.0269	uM
(E)-3-[1-[(2,4-dichlorophenyl)methyl]-5-fluoro-3-methylindol-7-yl]-N-(4,5-dichlorothiophen-2-yl)sulfonylprop-2-enamide	445684: Inhibition of human CYP2C9	ic50	0.0300	uM
3-(6-imidazol-1-yl-4-methyl-1H-benzimidazol-2-yl)-4-(pyridin-2-ylmethylamino)-1H-pyridin-2-one	290575: Inhibition of CYP2C9 in microsomes	ic50	0.0300	uM
5-chloro-2-fluoro-4-[[(6S)-5-(4-fluorophenyl)-1,2,3,6-tetrahydropyridin-6-yl]methylamino]-N-(1,3-thiazol-2-yl)benzenesulfonamide	1449857: Inhibition of CYP2C9 in human liver microsomes using diclofenac as substrate preincubated for 10 mins followed by substrate addition measured after 10 mins in presence of NADPH by LC-MS/MS analysis	ic50	0.0330	uM
N-naphthalen-2-yl-2-pyridin-4-ylquinoline-4-carboxamide	413199: Inhibition of reconstituted CYP2C9	ki	0.0330	uM
8-imidazol-1-yl-5,6,7,8-tetrahydroquinoline	2022035: Inhibition of CYP450 (unknown origin)	ic50	0.0335	uM
4-[3-[(2R,3R)-3-(2,4-difluorophenyl)-3-hydroxy-4-(1,2,4-triazol-1-yl)butan-2-yl]oxyprop-1-ynyl]benzonitrile	2131804: Inhibition of human CYP2C9 using diclofenac as substrate prewarmed for 10 mins followed by NADPH addition and measured after 10 mins by LC-MS/MS analysis	ic50	0.0340	uM
4-(4-tert-butylphenyl)sulfonyl-1-(1H-imidazol-5-ylmethyl)-2-(2-phenylethyl)-3,5-dihydro-2H-1,4-benzodiazepine	54407: Inhibitory activity against ccytochrome P450 2C9	ic50	0.0380	uM
(2R,3R)-2-(2,4-difluorophenyl)-3-(3-pyridin-4-ylprop-2-ynoxy)-1-(1,2,4-triazol-1-yl)butan-2-ol	2131804: Inhibition of human CYP2C9 using diclofenac as substrate prewarmed for 10 mins followed by NADPH addition and measured after 10 mins by LC-MS/MS analysis	ic50	0.0390	uM
N-[4-[[4-(benzotriazol-1-yl)pyrimidin-2-yl]amino]cyclohexyl]acetamide	769535: Inhibition of CYP2C9 (unknown origin)	ic50	0.0390	uM
(2-ethyl-1-benzofuran-3-yl)-(4-hydroxy-3,5-dimethylphenyl)methanone	282443: Inhibition of human CYP2C9	ki	0.0400	uM
4-[[(2S)-1-hydroxy-3-phenylpropan-2-yl]amino]-3-(6-imidazol-1-yl-4-methyl-1H-benzimidazol-2-yl)-1H-pyridin-2-one	290575: Inhibition of CYP2C9 in microsomes	ic50	0.0400	uM
5-(4-butoxyphenyl)-1,3-oxazole	54386: Concentration required to inhibit cytochrome P450 2C9.	ic50	0.0460	uM
4-(4-butoxyphenyl)pyridine	54386: Concentration required to inhibit cytochrome P450 2C9.	ic50	0.0460	uM
5-(4-butoxyphenyl)-1,2-thiazole	54386: Concentration required to inhibit cytochrome P450 2C9.	ic50	0.0460	uM
5-[3-[2-(trifluoromethyl)phenyl]phenyl]-1H-imidazole	502849: Inhibition of CYP2C9	ic50	0.0500	uM
[(2R)-1-[4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl]oxypropan-2-yl] 2-aminoacetate	316213: Inhibition of human CYP2C9	ic50	0.0630	uM
3-[6-methoxy-3-[(4-methoxyphenyl)methyl]naphthalen-2-yl]pyridine	364755: Inhibition of human recombinant CYP2C9 expressed in baculovirus-infected insect microsomes	ic50	0.0640	uM
methyl N-[(1R)-2-[(2S)-2-[[3-fluoro-4-[2-fluoro-4-[[(2S)-1-[(2R)-2-(methoxycarbonylamino)-2-phenylacetyl]pyrrolidine-2-carbonyl]amino]phenyl]phenyl]carbamoyl]pyrrolidin-1-yl]-2-oxo-1-phenylethyl]carbamate	1241909: Inhibition of human CYP2C9 by luminometry	ec50	0.0877	uM
1-(4-butoxyphenyl)-5-methylimidazole	54386: Concentration required to inhibit cytochrome P450 2C9.	ic50	0.0880	uM
(10bS)-7-acetyl-8,10-dihydroxy-3,9,10b-trimethyl-2H-[1]benzofuro[2,3-g]indazol-4-one	1922616: Inhibition of CYP2C9 in human liver microsomes	ic50	0.0940	uM
1-(4-butoxyphenyl)imidazole	54386: Concentration required to inhibit cytochrome P450 2C9.	ic50	0.0960	uM
N-[2-[[4-[4-[(3,4-dimethoxyphenyl)methyl]piperazin-1-yl]phenyl]carbamoyl]-4,5-dimethoxyphenyl]quinoline-3-carboxamide	295529: Inhibition of human CYP2C9 expressed in insect microsome after 45 mins	ic50	0.0968	uM
4-methyl-N-(2-phenylpyrazol-3-yl)benzenesulfonamide	54405: Binding affinity measured on human cytochrome P450 2C9 (CYP2C9) enzyme	ki	0.1000	uM
propan-2-yl 4-[1-(2-fluoro-4-methylsulfonylphenyl)pyrazolo[5,4-d]pyrimidin-4-yl]oxypiperidine-1-carboxylate	596036: Inhibition of CYP2C9	ki	0.1000	uM
4-[[(1R,6R)-6-amino-2-(4-fluorophenyl)cyclohex-2-en-1-yl]methylsulfanyl]-5-chloro-2-fluoro-N-(1,3-thiazol-2-yl)benzenesulfonamide;hydrochloride	1366221: Inhibition of CYP2C9 in human liver microsomes using diclofenac as substrate preincubated for 10 mins followed by substrate addition measured after 10 mins in presence of NADPH by LC-MS/MS analysis	ic50	0.1000	uM
4-[[(1R,6R)-6-amino-2-(4-fluorophenyl)cyclohex-2-en-1-yl]methoxy]-5-chloro-2-fluoro-N-(1,3-thiazol-2-yl)benzenesulfonamide;hydrochloride	1366221: Inhibition of CYP2C9 in human liver microsomes using diclofenac as substrate preincubated for 10 mins followed by substrate addition measured after 10 mins in presence of NADPH by LC-MS/MS analysis	ic50	0.1000	uM
N-phenyl-2-pyridin-4-ylquinoline-4-carboxamide	413199: Inhibition of reconstituted CYP2C9	ki	0.1000	uM
N’-(4-butyl-2-methylphenyl)-N-hydroxymethanimidamide	1860379: Inhibition of CYP2C9 in human kidney microsomes assessed as inhibition of 20-HETE formation using 7-methoxy-4-trifluoromethylcoumarin as substrate in presence of arachidonic acid and NADPH by fluorescence assay	ic50	0.1000	uM
5-(2,4,5-trichlorophenoxy)pyridin-2-amine	1416595: Inhibition of CYP2C9 (unknown origin)	ic50	0.1000	uM
3-(3,5-dibromo-4-hydroxybenzoyl)-2-ethylchromen-4-one	313084: Inhibition of CYP2C9	ki	0.1010	uM
6-(2-methylsulfonylpropan-2-yl)-8-(3-pyridin-4-ylphenyl)quinoline	314159: Inhibition of CYP2C9	ic50	0.1100	uM
6-methoxy-N-(oxan-4-ylmethyl)-3-[[4-(triazol-1-ylmethyl)naphthalene-1-carbonyl]amino]pyridine-2-carboxamide	724237: Inhibition of human recombinant CYP2C9 expressed in Escherichia coli cells	ic50	0.1100	uM
N-(naphthalen-1-ylmethyl)-2-pyridin-4-ylquinoline-4-carboxamide	413202: Inhibition of purified CYP2C9	ki	0.1130	uM
methyl N-[(1R)-2-[(2S)-2-[[3-chloro-4-[2-chloro-4-[[(2S)-1-[(2R)-2-(methoxycarbonylamino)-2-phenylacetyl]pyrrolidine-2-carbonyl]amino]phenyl]phenyl]carbamoyl]pyrrolidin-1-yl]-2-oxo-1-phenylethyl]carbamate	1241909: Inhibition of human CYP2C9 by luminometry	ec50	0.1160	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Warfarin	affects metabolic processing, decreases hydroxylation, decreases response to substance, decreases activity, affects response to substance (+14 more)	192
Diclofenac	affects metabolic processing, increases metabolic processing, affects hydrolysis, increases response to substance, affects response to substance (+13 more)	47
Sulfaphenazole	increases chemical synthesis, increases oxidation, decreases metabolic processing, decreases expression, decreases reaction (+8 more)	33
Tolbutamide	increases hydroxylation, decreases reaction, decreases metabolic processing, increases chemical synthesis, increases hydrolysis (+6 more)	33
Rifampin	increases activity, affects response to substance, decreases reaction, increases expression, affects cotreatment (+2 more)	29
Phenytoin	affects reaction, increases expression, increases activity, decreases activity, increases response to substance (+9 more)	24
Phenobarbital	affects cotreatment, affects metabolic processing, decreases reaction, increases expression, decreases activity (+1 more)	11
4’-hydroxydiclofenac	increases metabolic processing, affects abundance, affects metabolic processing, decreases activity, increases chemical synthesis (+4 more)	9
Ibuprofen	decreases metabolic processing, affects metabolic processing, affects response to substance, affects binding, increases metabolic processing (+1 more)	9
Acenocoumarol	affects response to substance, affects metabolic processing, increases metabolic processing, increases response to substance	8
Flurbiprofen	decreases reaction, increases hydroxylation, affects hydroxylation, increases reaction, affects metabolic processing (+5 more)	8
Benzbromarone	decreases activity, affects metabolic processing, decreases reaction, affects hydroxylation, increases reaction (+1 more)	7
Ticrynafen	affects metabolic processing, increases metabolic processing, increases response to substance, decreases reaction, decreases activity (+1 more)	7
Amiodarone	decreases reaction, increases reaction, increases metabolic processing, decreases activity, decreases chemical synthesis (+3 more)	6
Ketoconazole	increases expression, decreases activity, decreases expression, increases metabolic processing, affects metabolic processing (+4 more)	6
Valproic Acid	increases response to substance, increases metabolic processing, decreases expression, increases expression	6
Fluconazole	affects metabolic processing, affects reaction, affects binding, decreases activity, decreases reaction (+1 more)	6
Losartan	decreases reaction, increases hydroxylation, affects metabolic processing, increases metabolic processing	6
7-hydroxywarfarin	affects metabolic processing, increases metabolic processing, decreases reaction, increases chemical synthesis, increases hydroxylation (+2 more)	5
Resveratrol	affects cotreatment, decreases expression, decreases reaction, increases metabolic processing, decreases activity	5
Cyclophosphamide	increases metabolic processing, increases response to substance, increases activity, affects cotreatment, decreases reaction	5
Naproxen	affects metabolic processing, increases reaction, decreases methylation, increases metabolic processing	5
Plant Extracts	affects cotreatment, decreases expression, decreases activity	5
Quercetin	decreases reaction, increases hydroxylation, affects cotreatment, increases metabolic processing, decreases activity (+1 more)	5
Clopidogrel	affects reaction, affects response to substance, decreases metabolic processing, increases cleavage, increases oxidation	4
Carbamazepine	affects response to substance, affects metabolic processing, increases activity, increases expression, affects cotreatment	4
Methoxychlor	decreases methylation, decreases activity, affects cotreatment	4
Miconazole	affects binding, affects metabolic processing, decreases reaction, increases hydroxylation, increases abundance (+1 more)	4
Piroxicam	affects metabolic processing, increases metabolic processing, decreases reaction	4
Tobacco Smoke Pollution	decreases expression, increases expression	4

ChEMBL screening assays

3498 unique, capped per target: 3425 admet, 71 binding, 1 functional, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1000512	ADMET	Inhibition of human recombinant CYP2C9 expressed in insect microsomes	Discovery of (R)-4-(8-fluoro-2-oxo-1,2-dihydroquinazolin-3(4H)-yl)-N-(3-(7-methyl-1H-indazol-5-yl)-1-oxo-1-(4-(piperidin-1-yl)piperidin-1-yl)propan-2-yl)piperidine-1-carboxamide (BMS-694153): a potent antagonist of the human calcitonin gene-related peptide receptor for migraine with rapid and efficient intranasal exposure. — J Med Chem
CHEMBL1678447	Binding	Inhibition of human CYP2C9	Discovery, synthesis, and structure-activity relationship development of a series of N-(4-acetamido)phenylpicolinamides as positive allosteric modulators of metabotropic glutamate receptor 4 (mGlu(4)) with CNS exposure in rats. — J Med Chem
CHEMBL1741325	Functional	PUBCHEM_BIOASSAY: Cytochrome panel assay with activity outcomes. (Class of assay: other) Panel member name: p450-cyp2c9 Compounds with AC50 equal or less than 10 uM are considered active	PubChem BioAssay data set

Cellosaurus cell lines

49 cell lines: 45 transformed cell line, 3 finite cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_5B51	GM07038	Transformed cell line	Male
CVCL_5B91	GM10858	Transformed cell line	Male
CVCL_5E79	GM12841	Transformed cell line	Female
CVCL_5E94	GM12863	Transformed cell line	Female
CVCL_5F21	GM12912	Transformed cell line	Female
CVCL_5V30	GM15029	Transformed cell line	Sex unspecified
CVCL_5V46	GM15050	Transformed cell line	Sex unspecified
CVCL_5W48	GM15216	Transformed cell line	Sex unspecified
CVCL_5W58	GM15228	Transformed cell line	Sex unspecified
CVCL_5W68	GM15242	Transformed cell line	Sex unspecified

Clinical trials (associated diseases)

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