CYP2C18

Summary

CYP2C18 (cytochrome P450 family 2 subfamily C member 18, HGNC:2620) is a protein-coding gene on chromosome 10q23.33, encoding Cytochrome P450 2C18 (P33260). A cytochrome P450 monooxygenase involved in retinoid metabolism.

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 but its specific substrate has not yet been determined. The gene is located within a cluster of cytochrome P450 genes on chromosome 10q24. An additional gene, CYP2C17, was once thought to exist; however, CYP2C17 is now considered an artefact based on a chimera of CYP2C18 and CYP2C19. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 1562 — RefSeq curated summary.

At a glance

• GWAS associations: 14
• Clinical variants (ClinVar): 95 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000772

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2620
Approved symbol	CYP2C18
Name	cytochrome P450 family 2 subfamily C member 18
Location	10q23.33
Locus type	gene with protein product
Status	Approved
Aliases	P450IIC17, CPCI, CYP2C
Ensembl gene	ENSG00000108242
Ensembl biotype	protein_coding
OMIM	601131
Entrez	1562

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000285979, ENST00000339022, ENST00000867040

RefSeq mRNA: 2 — MANE Select: NM_000772 NM_000772, NM_001128925

CCDS: CCDS44460, CCDS7435

Canonical transcript exons

ENST00000285979 — 9 exons

Exon	Start	End
ENSE00001893364	94735263	94736190
ENSE00001895878	94683729	94683987
ENSE00002434776	94688125	94688274
ENSE00003266049	94687770	94687932
ENSE00003520658	94724346	94724533
ENSE00003528047	94706784	94706960
ENSE00003609077	94733297	94733438
ENSE00003649740	94720396	94720537
ENSE00003684873	94694917	94695077

Expression profiles

Bgee: expression breadth ubiquitous, 113 present calls, max score 98.65.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3334 / max 113.1125, expressed in 45 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
106339	0.1395	32
106333	0.0565	15
106336	0.0529	18
106337	0.0302	12
106338	0.0250	11
106334	0.0203	11
106335	0.0090	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	98.65	gold quality
tongue squamous epithelium	UBERON:0006919	97.59	gold quality
pancreatic ductal cell	CL:0002079	96.15	gold quality
ileal mucosa	UBERON:0000331	95.67	gold quality
right lobe of liver	UBERON:0001114	95.16	gold quality
liver	UBERON:0002107	94.44	gold quality
duodenum	UBERON:0002114	94.18	gold quality
esophagus squamous epithelium	UBERON:0006920	92.16	gold quality
epithelium of esophagus	UBERON:0001976	92.15	gold quality
squamous epithelium	UBERON:0006914	92.05	gold quality
cervix squamous epithelium	UBERON:0006922	91.36	silver quality
oral cavity	UBERON:0000167	91.27	gold quality
gingiva	UBERON:0001828	91.08	gold quality
gingival epithelium	UBERON:0001949	90.07	gold quality
esophagus mucosa	UBERON:0002469	89.70	gold quality
cervix epithelium	UBERON:0004801	89.34	gold quality
pharyngeal mucosa	UBERON:0000355	87.95	gold quality
lower esophagus mucosa	UBERON:0035834	87.48	gold quality
gall bladder	UBERON:0002110	84.74	gold quality
epithelium of nasopharynx	UBERON:0001951	83.35	silver quality
epithelial cell of pancreas	CL:0000083	81.80	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.57	silver quality
small intestine	UBERON:0002108	81.01	gold quality
small intestine Peyer’s patch	UBERON:0003454	80.46	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.58	silver quality
body of tongue	UBERON:0011876	77.94	gold quality
mammalian vulva	UBERON:0000997	76.71	gold quality
tongue	UBERON:0001723	76.52	gold quality
jejunum	UBERON:0002115	75.77	gold quality
mucosa of transverse colon	UBERON:0004991	75.10	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.12

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR1I2, NR1I3

miRNA regulators (miRDB)

47 targeting CYP2C18, 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-5692A	100.00	74.40	6850
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-4804-3P	99.65	67.78	866
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-2113	99.58	71.22	1521
HSA-MIR-888-3P	99.53	69.77	1057
HSA-MIR-642A-5P	99.51	65.10	1152
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-4797-5P	99.39	68.01	1354
HSA-MIR-6853-3P	99.36	70.79	1558
HSA-MIR-6882-5P	99.35	71.13	1206
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-888-5P	99.30	70.15	1855
HSA-MIR-1843	98.97	66.07	838
HSA-MIR-4802-5P	98.97	66.26	833
HSA-MIR-6760-5P	98.87	66.73	1515
HSA-MIR-760	98.81	66.65	1392
HSA-MIR-323A-5P	98.59	65.13	651

Literature-anchored findings (GeneRIF, showing 3)

• Despite the observed alterations, tg-CYP2C18&19 did not show any macroscopic or microscopic pathology at the examined age. Hence, these hemizygous transgenic mice were considered to be viable and healthy animals. (PMID:19038035)
• These results suggest that there is no notable influence of sequence variation in the CYP2C genes on longevity in the examined German population (PMID:21798861)
• A Novel CYP2C-Haplotype Associated With Ultrarapid Metabolism of Escitalopram. (PMID:33759177)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cyp2c55	ENSMUSG00000025002
rattus_norvegicus	Cyp2c55	ENSRNOG00000001466
rattus_norvegicus	Cyp2c24	ENSRNOG00000013241
rattus_norvegicus	Cyp2c11	ENSRNOG00000052810

Paralogs (15): CYP2W1 (ENSG00000073067), CYP2D6 (ENSG00000100197), CYP2E1 (ENSG00000130649), CYP2J2 (ENSG00000134716), CYP2C9 (ENSG00000138109), 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 2C18 — P33260 (reviewed: P33260)

Alternative names: CYPIIC18, Cytochrome P450-6b/29c

All UniProt accessions (1): P33260

UniProt curated annotations — full annotation on UniProt →

Function. A cytochrome P450 monooxygenase involved in retinoid metabolism. Hydroxylates all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may modulate atRA signaling and clearance. 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 (CPR; NADPH-ferrihemoprotein reductase).

Subcellular location. Endoplasmic reticulum membrane. Microsome membrane.

Pathway. Cofactor metabolism; retinol metabolism.

Similarity. Belongs to the cytochrome P450 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P33260-1	1	yes
P33260-2	2

RefSeq proteins (2): NP_000763, NP_001122397 (=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

Catalyzed reactions (Rhea), 2 shown:

• an organic molecule + reduced [NADPH–hemoprotein reductase] + O2 = an alcohol + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:17149)
• all-trans-retinoate + reduced [NADPH–hemoprotein reductase] + O2 = all-trans-4-hydroxyretinoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:51984)

UniProt features (5 total): signal peptide 1, chain 1, binding site 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2CIK	X-RAY DIFFRACTION	1.75
2H6P	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P33260-F1	93.93	0.83

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

1 pathways

ID	Pathway
R-HSA-211981	Xenobiotics

MSigDB gene sets: 122 (showing top): REACTOME_BIOLOGICAL_OXIDATIONS, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_DN, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_LONG_CHAIN_FATTY_ACID_METABOLIC_PROCESS, GOBP_RETINOL_METABOLIC_PROCESS, MODULE_16, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, HSIAO_LIVER_SPECIFIC_GENES, CAIRO_HEPATOBLASTOMA_DN, GOBP_RETINOIC_ACID_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS

GO Biological Process (10): xenobiotic metabolic process (GO:0006805), epoxygenase P450 pathway (GO:0019373), xenobiotic catabolic process (GO:0042178), retinol metabolic process (GO:0042572), retinoic acid metabolic process (GO:0042573), linoleic acid metabolic process (GO:0043651), lipid metabolic process (GO:0006629), terpenoid metabolic process (GO:0006721), arachidonate metabolic process (GO:0019369), monocarboxylic acid metabolic process (GO:0032787)

GO Molecular Function (11): 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), oxygen binding (GO:0019825), heme binding (GO:0020037), linoleic acid epoxygenase activity (GO:0071614), 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-1 pathways:

Category	Pathways
Cytochrome P450 - arranged by substrate type	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
olefinic compound metabolic process	3
monooxygenase activity	3
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	3
retinoid metabolic process	2
hormone metabolic process	2
long-chain fatty acid metabolic process	2
unsaturated fatty acid metabolic process	2
oxidoreductase activity	2
cellular anatomical structure	2
metabolic process	1
cellular response to xenobiotic stimulus	1
arachidonate metabolic process	1
xenobiotic metabolic process	1
catabolic process	1
primary alcohol metabolic process	1
monocarboxylic acid metabolic process	1
primary metabolic process	1
isoprenoid metabolic process	1
icosanoid metabolic process	1
carboxylic acid metabolic process	1
transition metal ion binding	1
arachidonate monooxygenase activity	1
small molecule binding	1
tetrapyrrole 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
cell periphery	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1542 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CYP2C18	AP1AR	Q63HQ0	911
CYP2C18	PPIG	Q13427	814
CYP2C18	HTR7	P34969	757
CYP2C18	KIF20B	Q96Q89	753
CYP2C18	RBP4	P02753	712
CYP2C18	EPHX2	P34913	685
CYP2C18	ENTPD1	P49961	648
CYP2C18	NR1I2	O75469	601
CYP2C18	GSTA1	P08263	546
CYP2C18	NR1I3	Q14994	540
CYP2C18	CYP3A7	P24462	533
CYP2C18	UGT1A6	P19224	516
CYP2C18	CYP1A1	P04798	513
CYP2C18	VKORC1	Q9BQB6	507
CYP2C18	GRIP1	Q9Y3R0	495

IntAct

10 interactions, top by confidence:

A	B	Type	Score
CYP2C18	CYP2C9	psi-mi:“MI:0914”(association)	0.530
CYP2C18	A2M	psi-mi:“MI:0915”(physical association)	0.370
CYP2C18	ECSIT	psi-mi:“MI:0915”(physical association)	0.370
CYP2C18	SDC2	psi-mi:“MI:0915”(physical association)	0.370
TMEM260	MYH3	psi-mi:“MI:0914”(association)	0.350
CYP2C19	MFN2	psi-mi:“MI:0914”(association)	0.350
CYP2C18	PGRMC1	psi-mi:“MI:0914”(association)	0.350

BioGRID (32): ACAD8 (Affinity Capture-MS), CYP2C9 (Affinity Capture-MS), SLC7A2 (Affinity Capture-MS), AMZ2 (Affinity Capture-MS), CYP2C18 (Affinity Capture-MS), CYP2C9 (Affinity Capture-MS), CYP2C18 (Affinity Capture-MS), SLC7A2 (Affinity Capture-MS), CYP2C18 (Affinity Capture-MS), SLC7A2 (Affinity Capture-MS), CYP2C18 (Affinity Capture-MS), CYP2C9 (Affinity Capture-MS), CDK16 (Affinity Capture-MS), PDZD8 (Affinity Capture-MS), SLC12A7 (Affinity Capture-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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	65
Likely benign	11
Benign	7

Top pathogenic / likely-pathogenic (0)

SpliceAI

1586 predictions. Top by Δscore:

Variant	Effect	Δscore
10:94687894:G:GT	donor_gain	1.0000
10:94687927:GAC:G	donor_gain	1.0000
10:94688124:GGA:G	acceptor_gain	1.0000
10:94688235:G:GT	donor_gain	1.0000
10:94688256:GAGT:G	donor_gain	1.0000
10:94688275:G:A	donor_loss	1.0000
10:94722795:GGGT:G	donor_gain	1.0000
10:94733291:TTTCA:T	acceptor_loss	1.0000
10:94733292:TTCA:T	acceptor_loss	1.0000
10:94733292:TTCAG:T	acceptor_loss	1.0000
10:94733293:TCA:T	acceptor_loss	1.0000
10:94733293:TCAG:T	acceptor_loss	1.0000
10:94733294:CA:C	acceptor_loss	1.0000
10:94733294:CAGGG:C	acceptor_loss	1.0000
10:94733295:A:AC	acceptor_loss	1.0000
10:94733295:A:AG	acceptor_gain	1.0000
10:94733295:AG:A	acceptor_gain	1.0000
10:94733295:AGG:A	acceptor_gain	1.0000
10:94733296:G:GA	acceptor_gain	1.0000
10:94733296:G:GG	acceptor_gain	1.0000
10:94733296:G:GT	acceptor_loss	1.0000
10:94733296:GG:G	acceptor_gain	1.0000
10:94733296:GGG:G	acceptor_gain	1.0000
10:94733296:GGGC:G	acceptor_gain	1.0000
10:94733296:GGGCA:G	acceptor_gain	1.0000
10:94733416:C:G	donor_gain	1.0000
10:94733434:AGCAG:A	donor_loss	1.0000
10:94733435:GCAG:G	donor_gain	1.0000
10:94733435:GCAGG:G	donor_loss	1.0000
10:94733436:CAGGT:C	donor_loss	1.0000

AlphaMissense

3270 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:94733429:T:C	F428L	0.995
10:94733431:C:A	F428L	0.995
10:94733431:C:G	F428L	0.995
10:94724432:G:C	A350P	0.992
10:94724455:A:C	R357S	0.991
10:94724455:A:T	R357S	0.991
10:94724454:G:C	R357T	0.989
10:94733381:T:C	F412L	0.989
10:94733383:T:A	F412L	0.989
10:94733383:T:G	F412L	0.989
10:94733348:T:C	F401L	0.987
10:94733350:C:A	F401L	0.987
10:94733350:C:G	F401L	0.987
10:94688169:T:C	F126L	0.981
10:94688171:C:A	F126L	0.981
10:94688171:C:G	F126L	0.981
10:94688238:G:C	A149P	0.980
10:94733429:T:A	F428I	0.979
10:94687892:A:C	R97S	0.977
10:94687892:A:T	R97S	0.977
10:94724445:A:T	E354V	0.977
10:94688164:G:C	R124P	0.975
10:94688188:G:C	R132P	0.975
10:94733307:T:A	I387K	0.974
10:94735263:G:A	G431E	0.974
10:94735307:T:C	F446L	0.974
10:94735309:T:A	F446L	0.974
10:94735309:T:G	F446L	0.974
10:94735269:G:C	R433P	0.973
10:94687881:T:C	F94L	0.972

dbSNP variants (sampled 300 via entrez): RS1000068655 (10:94735516 C>G,T), RS1000196127 (10:94695193 G>A), RS1000398501 (10:94722159 T>A), RS1000610541 (10:94699761 C>G,T), RS1000659112 (10:94710144 T>C), RS1000720513 (10:94704427 G>A,T), RS1000769992 (10:94704194 C>A), RS1000861846 (10:94687235 C>T), RS1000942250 (10:94713073 T>C), RS1001004781 (10:94694068 G>T), RS1001095733 (10:94717283 T>C), RS1001118600 (10:94694260 G>C), RS1001139766 (10:94735702 C>A), RS1001148170 (10:94717067 G>A,C,T), RS1001299753 (10:94723350 G>A)

Disease associations

OMIM: gene MIM:601131 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST000436_1	Acenocoumarol maintenance dosage	8.000000e-12
GCST000467_1	Response to clopidogrel therapy	2.000000e-13
GCST002061_1	Warfarin maintenance dose	5.000000e-12
GCST004264_1	Clopidogrel active metabolite levels	1.000000e-14
GCST004266_1	Response to clopidogrel therapy	1.000000e-16
GCST005182_5	Common carotid intima-media thickness in HIV negative individuals	5.000000e-06
GCST006206_3	Thiopurine-induced alopecia in inflammatory bowel disease	1.000000e-06
GCST006249_39	Serum metabolite levels	7.000000e-23
GCST006249_64	Serum metabolite levels	4.000000e-26
GCST007684_2	Plasma clozapine-norclozapine ratio in treatment-resistant schizophrenia	5.000000e-14
GCST008374_1	Warfarin maintenance dose (adjusted for clinical factors)	3.000000e-11
GCST90002404_495	Red cell distribution width	1.000000e-09
GCST90011900_60	Serum alkaline phosphatase levels	2.000000e-10
GCST90013407_40	Liver enzyme levels (gamma-glutamyl transferase)	9.000000e-11

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0007966	clopidogrel metabolite measurement
EFO:0600040	plasma clozapine-to-N-desmethylclozapine ratio measurement
EFO:0009188	Red cell distribution width
EFO:0004533	alkaline phosphatase measurement
EFO:0004532	serum gamma-glutamyl transferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2408 (SINGLE PROTEIN), CHEMBL4523986 (PROTEIN FAMILY), CHEMBL6066546 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 19,605 (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
CHEMBL1109	SULFAPHENAZOLE	4	4,065
CHEMBL477772	PAZOPANIB	4	15,540

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

PharmGKB variants

6 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2901783	CYP2C18		0.00	0
rs1126545	CYP2C18		0.00	0
rs2860840	CYP2C18		0.00	0
rs11188059	CYP2C18		0.00	0
rs41291550	CYP2C18		0.00	0
rs1042192	CYP2C18		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — CYP2 family: drug metabolising subset

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
compound 9 [PMID: 11606127]	Inhibition	5.52	pIC50

ChEMBL bioactivities

30 potent at pChembl≥5 of 40 total, top 30 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.60	IC50	251.2	nM	CHEMBL601428
6.16	IC50	700	nM	CHEMBL3330409
6.05	IC50	900	nM	CHEMBL3330410
5.96	IC50	1100	nM	CHEMBL2130955
5.72	IC50	1900	nM	CHEMBL2130955
5.60	IC50	2500	nM	CHEMBL5612347
5.55	IC50	2800	nM	CHEMBL2130955
5.52	IC50	3000	nM	CHEMBL121503
5.52	IC50	3000	nM	CHEMBL121323
5.43	IC50	3700	nM	CHEMBL5406721
5.43	IC50	3700	nM	CHEMBL46909
5.42	IC50	3800	nM	CHEMBL5418617
5.41	IC50	3900	nM	CHEMBL5429178
5.40	IC50	4000	nM	CHEMBL121420
5.31	IC50	4900	nM	CHEMBL2130955
5.30	IC50	5000	nM	CHEMBL120426
5.23	IC50	5900	nM	CHEMBL5406218
5.23	IC50	5900	nM	CHEMBL5857118
5.22	IC50	6053	nM	CHEMBL65590
5.22	IC50	6000	nM	CHEMBL331485
5.16	IC50	7000	nM	CHEMBL120797
5.16	IC50	7000	nM	CHEMBL330871
5.10	IC50	7900	nM	PAZOPANIB
5.10	IC50	8000	nM	CHEMBL121522
5.10	IC50	8000	nM	CHEMBL120183
5.05	IC50	9000	nM	CHEMBL414238
5.05	IC50	9000	nM	CHEMBL121048
5.02	IC50	9500	nM	CHEMBL5784006
5.00	IC50	1e+04	nM	CHEMBL5395150
5.00	IC50	1e+04	nM	CHEMBL333704

PubChem BioAssay actives

30 with measured affinity, of 509 total; 27 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
8-imidazol-1-yl-5,6,7,8-tetrahydroquinoline	2022035: Inhibition of CYP450 (unknown origin)	ic50	0.0335	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
2-(dimethylamino)-2-(2-ethylphenyl)-N-[3-(3-sulfamoylphenyl)-1H-indazol-5-yl]acetamide	2119433: Inhibition of CYP450 (unknown origin)	ic50	0.7000	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
2-[4-(trifluoromethyl)phenyl]chromen-4-one	1860369: Inhibition of CYP450 in human HCT-116 cells assessed as 20-HETE formation in presence of arachidonic acid incubated for 15 mins by multi-enzyme assay based LC-MS/MS analysis	ic50	1.1000	uM
4-N-[(1S)-1,2,3,4-tetrahydronaphthalen-1-yl]-4-N-[[(7R)-5,6,7,8-tetrahydro-1,6-naphthyridin-7-yl]methyl]cyclohexane-1,4-diamine	2124397: Inhibition of CYP450 (unknown origin)	ic50	2.5000	uM
4-(3-aminophenyl)-N-(3-hydroxypropyl)-N-(2-phenylpyrazol-3-yl)benzenesulfonamide	54374: Inhibitory effect on human recombinant liver cytochrome P450 2C18 expressed in yeast strain	ic50	3.0000	uM
4-amino-N-(2-phenylpyrazol-3-yl)-N-propan-2-ylbenzenesulfonamide	54374: Inhibitory effect on human recombinant liver cytochrome P450 2C18 expressed in yeast strain	ic50	3.0000	uM
1-[3-(2,4-dimethoxyphenyl)phenyl]-2,4-dimethoxybenzene	1973305: Inhibition of CYP450 in pooled human liver microsomes in presence of NADPH measured every 3 mins for 120 mins by fluorescence based analysis	ic50	3.7000	uM
1-[(E)-2-(2,4-dimethoxyphenyl)ethenyl]-3,5-dimethoxybenzene	1973305: Inhibition of CYP450 in pooled human liver microsomes in presence of NADPH measured every 3 mins for 120 mins by fluorescence based analysis	ic50	3.7000	uM
2,4-bis(3,5-dimethoxyphenyl)pyrimidine	1973305: Inhibition of CYP450 in pooled human liver microsomes in presence of NADPH measured every 3 mins for 120 mins by fluorescence based analysis	ic50	3.8000	uM
2,5-bis(3,5-dimethoxyphenyl)thiophene	1973305: Inhibition of CYP450 in pooled human liver microsomes in presence of NADPH measured every 3 mins for 120 mins by fluorescence based analysis	ic50	3.9000	uM
N-(4-hydroxybutyl)-4-(3-nitrophenyl)-N-(2-phenylpyrazol-3-yl)benzenesulfonamide	54374: Inhibitory effect on human recombinant liver cytochrome P450 2C18 expressed in yeast strain	ic50	4.0000	uM
4-(3-nitrophenyl)-N-(2-phenylpyrazol-3-yl)benzenesulfonamide	54374: Inhibitory effect on human recombinant liver cytochrome P450 2C18 expressed in yeast strain	ic50	5.0000	uM
4-[2-(2,4-dimethoxyphenyl)-1,3-thiazol-4-yl]phenol	1973305: Inhibition of CYP450 in pooled human liver microsomes in presence of NADPH measured every 3 mins for 120 mins by fluorescence based analysis	ic50	5.9000	uM
4-amino-N-butyl-N-(2-phenylpyrazol-3-yl)benzenesulfonamide	54374: Inhibitory effect on human recombinant liver cytochrome P450 2C18 expressed in yeast strain	ic50	6.0000	uM
1-pyridin-4-yl-1a,2,3,7b-tetrahydro-1H-cyclopropa[a]naphthalen-4-ol	2022025: Inhibition of CYP450 in human liver microsomes	ic50	6.0534	uM
4-amino-N-benzyl-N-(2-phenylpyrazol-3-yl)benzenesulfonamide	54374: Inhibitory effect on human recombinant liver cytochrome P450 2C18 expressed in yeast strain	ic50	7.0000	uM
4-amino-N-ethyl-N-(2-phenylpyrazol-3-yl)benzenesulfonamide	54374: Inhibitory effect on human recombinant liver cytochrome P450 2C18 expressed in yeast strain	ic50	7.0000	uM
(5R)-3-[1-(1H-indol-2-ylmethyl)piperidin-4-yl]-5-(6-methoxyquinolin-4-yl)-1,3-oxazolidin-2-one	306257: Inhibition of CYP450	ic50	7.9433	uM
4-amino-N-(2-phenylpyrazol-3-yl)-N-propylbenzenesulfonamide	54374: Inhibitory effect on human recombinant liver cytochrome P450 2C18 expressed in yeast strain	ic50	8.0000	uM
N-(3-hydroxypropyl)-4-(3-nitrophenyl)-N-(2-phenylpyrazol-3-yl)benzenesulfonamide	54374: Inhibitory effect on human recombinant liver cytochrome P450 2C18 expressed in yeast strain	ic50	8.0000	uM
4-amino-N-(3-methylbutyl)-N-(2-phenylpyrazol-3-yl)benzenesulfonamide	54374: Inhibitory effect on human recombinant liver cytochrome P450 2C18 expressed in yeast strain	ic50	9.0000	uM
N-(2-hydroxyethyl)-4-(3-nitrophenyl)-N-(2-phenylpyrazol-3-yl)benzenesulfonamide	54374: Inhibitory effect on human recombinant liver cytochrome P450 2C18 expressed in yeast strain	ic50	9.0000	uM
3-[1-[(3,4-dimethylphenyl)methyl]piperidin-4-yl]-5-(6-methoxyquinolin-4-yl)-1,3-oxazolidin-2-one	306257: Inhibition of CYP450	ic50	10.0000	uM
N-methyl-N-(2-phenylpyrazol-3-yl)-4-prop-2-enylbenzenesulfonamide	54374: Inhibitory effect on human recombinant liver cytochrome P450 2C18 expressed in yeast strain	ic50	10.0000	uM
1-[3-(3,5-dimethoxyphenyl)phenyl]-3,5-dimethoxybenzene	1973305: Inhibition of CYP450 in pooled human liver microsomes in presence of NADPH measured every 3 mins for 120 mins by fluorescence based analysis	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression, affects cotreatment	3
Ifosfamide	increases reaction, increases activity, increases metabolic processing, increases response to substance	3
Aflatoxin B1	decreases methylation, affects expression, decreases expression	3
Benzo(a)pyrene	decreases expression, decreases methylation, affects methylation	2
Cyclophosphamide	increases activity, increases response to substance, increases reaction	2
Rifampin	decreases expression	2
Cyclosporine	decreases expression, affects cotreatment	2
aristolochic acid I	increases expression	1
sporidesmin	affects reaction, increases expression	1
propionaldehyde	increases expression	1
bisphenol A	affects cotreatment, increases methylation	1
senecionine	decreases expression	1
sodium arsenate	increases abundance, decreases expression	1
hydroxyhydroquinone	increases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	increases expression	1
triflumuron	increases metabolic processing	1
1,4-naphthoquinone	increases abundance	1
desethylamodiaquine	increases abundance, increases metabolic processing	1
nefazodone	affects cotreatment, decreases expression	1
5-hydroxydiclofenac	affects cotreatment, increases abundance	1
1,1,1-trichloro-2-(4-hydroxyphenyl)-2-(4-methoxyphenyl)ethane	increases chemical synthesis	1
bisphenol S	affects cotreatment, increases methylation	1
5-hydroxythalidomide	increases metabolic processing	1
4,5-dihydropyrazole-1,5-dicarboxylic acid 1-((4-chlorophenyl)-amide) 5-(2-oxo-2H-(1,3’)bipyridinyl-6’-yl)-amide	increases metabolic processing	1
(+)-JQ1 compound	decreases expression	1
walrycin A	increases expression	1
2’-(glutathion-S-yl)-deschlorodiclofenac	increases abundance, affects cotreatment	1
Atazanavir Sulfate	affects cotreatment, decreases expression	1
Acenocoumarol	affects response to substance	1

ChEMBL screening assays

199 unique, capped per target: 196 admet, 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3529575	ADMET	Activity of human recombinant CYP2C18 assessed as enzyme-mediated 2-hydroxyethyl (1R,3aR,4aR,6R,8aR,9S,9aS)-9-((E)-2-(5-(3-fluorophenyl)pyridin-2-yl)vinyl)-1-methyl-3-oxododecahydronaphtho[2,3-c]furan-6-ylcarbamate formation at 25 uM after	Identification of human liver cytochrome P450 enzymes involved in the metabolism of SCH 530348 (Vorapaxar), a potent oral thrombin protease-activated receptor 1 antagonist. — Drug Metab Dispos
CHEMBL4614611	Binding	Drug metabolism in human liver microsomes assessed as Cytochrome P450-mediated formation of 12-OHNVP by measuring Kcat/Km ratio in presence of NADPH regenerating reagents by uHPLC-MS/MS analysis	Twelfth-Position Deuteration of Nevirapine Reduces 12-Hydroxy-Nevirapine Formation and Nevirapine-Induced Hepatocyte Death. — J Med Chem

Cellosaurus cell lines

2 cell lines: 1 spontaneously immortalized cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_0U07	CHL-CYP2C18	Spontaneously immortalized cell line	Female
CVCL_UH00	HEK293 CYP2C18*1-V5	Transformed cell line	Female

Clinical trials (associated diseases)

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