CYP3A4

Summary

CYP3A4 (cytochrome P450 family 3 subfamily A member 4, HGNC:2637) is a protein-coding gene on chromosome 7q22.1, encoding Cytochrome P450 3A4 (P08684). A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids.

This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases that 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 glucocorticoids and some pharmacological agents. This enzyme is involved in the metabolism of approximately half the drugs in use today, including acetaminophen, codeine, cyclosporin A, diazepam, erythromycin, and chloroquine. The enzyme also metabolizes some steroids and carcinogens. This gene is part of a cluster of cytochrome P450 genes on chromosome 7q21.1. Previously another CYP3A gene, CYP3A3, was thought to exist; however, it is now thought that this sequence represents a transcript variant of CYP3A4. Alternatively spliced transcript variants encoding different isoforms have been identified.

Source: NCBI Gene 1576 — RefSeq curated summary.

At a glance

• Gene–disease (curated): vitamin D-dependent rickets, type 3 (Limited, GenCC)
• GWAS associations: 8
• Clinical variants (ClinVar): 40 total — 3 pathogenic
• Phenotypes (HPO): 15
• Druggable target: yes — 695 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_017460

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2637
Approved symbol	CYP3A4
Name	cytochrome P450 family 3 subfamily A member 4
Location	7q22.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000160868
Ensembl biotype	protein_coding
OMIM	124010
Entrez	1576

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 21 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000336411, ENST00000354593, ENST00000415003, ENST00000480043, ENST00000651162, ENST00000651514, ENST00000652018, ENST00000859200, ENST00000859201, ENST00000859202, ENST00000859203, ENST00000859204, ENST00000859205, ENST00000859206, ENST00000859207, ENST00000859208, ENST00000859209, ENST00000859210, ENST00000859211, ENST00000859212, ENST00000859213, ENST00000859214, ENST00000859215

RefSeq mRNA: 2 — MANE Select: NM_017460 NM_001202855, NM_017460

CCDS: CCDS5674

Canonical transcript exons

ENST00000651514 — 13 exons

Exon	Start	End
ENSE00002436830	99760819	99760981
ENSE00002497209	99784011	99784184
ENSE00002499538	99767131	99767258
ENSE00002499614	99779992	99780085
ENSE00002504817	99766377	99766443
ENSE00002510012	99762041	99762267
ENSE00002515593	99763855	99764015
ENSE00002527926	99769768	99769856
ENSE00002718292	99768354	99768502
ENSE00003474032	99772590	99772689
ENSE00003604860	99770122	99770235
ENSE00003628574	99778028	99778080
ENSE00003849134	99756967	99758228

Expression profiles

Bgee: expression breadth ubiquitous, 194 present calls, max score 99.94.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 7.9434 / max 4187.0158, expressed in 26 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
85116	7.7738	26
85117	0.1405	12
85118	0.0291	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	99.94	gold quality
ileal mucosa	UBERON:0000331	98.94	gold quality
liver	UBERON:0002107	98.73	gold quality
right lobe of liver	UBERON:0001114	98.36	gold quality
duodenum	UBERON:0002114	98.34	gold quality
olfactory bulb	UBERON:0002264	95.97	silver quality
buccal mucosa cell	CL:0002336	92.56	silver quality
small intestine Peyer’s patch	UBERON:0003454	90.67	gold quality
type B pancreatic cell	CL:0000169	90.51	gold quality
small intestine	UBERON:0002108	90.49	gold quality
jejunum	UBERON:0002115	89.36	gold quality
diaphragm	UBERON:0001103	88.99	gold quality
epithelial cell of pancreas	CL:0000083	88.55	silver quality
pancreatic ductal cell	CL:0002079	87.97	silver quality
cervix squamous epithelium	UBERON:0006922	87.21	gold quality
upper arm skin	UBERON:0004263	86.38	silver quality
mucosa of paranasal sinus	UBERON:0005030	86.00	gold quality
tongue squamous epithelium	UBERON:0006919	84.87	silver quality
CA1 field of hippocampus	UBERON:0003881	83.29	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.17	gold quality
hair follicle	UBERON:0002073	81.87	gold quality
inferior vagus X ganglion	UBERON:0005363	81.69	silver quality
ventral tegmental area	UBERON:0002691	81.53	silver quality
subthalamic nucleus	UBERON:0001906	81.32	silver quality
body of pancreas	UBERON:0001150	81.23	gold quality
periodontal ligament	UBERON:0008266	80.89	silver quality
male germ cell	CL:0000015	80.68	gold quality
cardia of stomach	UBERON:0001162	80.44	silver quality
dorsal plus ventral thalamus	UBERON:0001897	80.33	silver quality
vena cava	UBERON:0004087	79.87	silver quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	1258.13
E-ANND-3	yes	9.68
E-ENAD-17	no	49.39

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BHLHE40, CEBPA, CEBPB, CEBPG, DBP, ESR1, FOXA1, FOXA2, FOXA3, FOXM1, HDAC1, HNF1A, HNF4A, HR, MYC, NCOA1, NCOA2, NCOA6, NCOR1, NCOR2, NFIL3, NFKB, NR0B2, NR1H3, NR1I2, NR1I3, NR2F1, NR2F2, NR3C1, ONECUT1, PPARA, RELA, RXRA, SP1, SP3, TCF3, THRA, TP53, USF1, VDR

miRNA regulators (miRDB)

69 targeting CYP3A4, 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-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-609	99.82	64.26	505
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-2116-3P	99.74	64.32	889
HSA-MIR-4255	99.72	67.70	1541
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-4666B	99.64	68.69	1282
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-766-5P	99.47	67.91	2225

Literature-anchored findings (GeneRIF, showing 40)

• There is a correlation between the CYP3A4*1B allele and early menarche, but this difference disappears when corrected for ethnicity and birth year. (PMID:11749050)
• Comparative aflatoxin B(1) activation and cytotoxicity in human bronchial cells expressing cytochromes P450 1A2 and 3A4. (PMID:11782366)
• 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)
• population screen on a panel of 101 human DNA samples of the 5’ proximal regulatory region of the CYP3A4 gene using non-radioactive single strand conformation polymorphism (SSCP) (PMID:11890939)
• presence of the ER6 motif of CYP3A4 mediates the high expression of CYP3A7 in subjects carrying CYP3A7*1C allele (PMID:11940601)
• expression in hepatocytes by vitamin D receptor pathway (PMID:11991950)
• xenobiotic inhibition of CYP3A4 promotor activity- role of the steroid and xenobiotic receptor (PMID:12072427)
• An association uncorrected for stratification was observed between CYP3A4-V and prostate cancer in African Americans (P=0.007). (PMID:12107441)
• Transcriptional regulation of the human CYP3A4 gene by the constitutive androstane receptor. (PMID:12130689)
• Polymorphism has no functional significance and is not associated with risk of breast or ovarian cancer. (PMID:12142725)
• change in vitamin D receptor-mediated mRNA induction in Caco-2 cells by altering cellular phosphorylation state (PMID:12147248)
• Efavirenz is an inducer of liver CYP3A4 but did not appear to induce intestinal CYP3A4 (PMID:12151999)
• CYP3A4 is the only P450 of those tested that converts tamoxifen to alpha-hydroxytamoxifen and the only one that results in appreciable levels of irreversible binding of tamoxifen to DNA. (PMID:12419838)
• description of CYP3A4 binding sites for diazepam and kinetic studies (PMID:12464248)
• CYP3A4 expression in the endometrium of premenopausal women is comparable between the secretory and proliferative phases. (PMID:12485945)
• Different alterations of cytochrome P450 3A4 isoform and its gene expression in livers of patients with chronic liver diseases. CYP3A4 isoenzyme and its activity declined among patients with hepatic cirrhosis. (PMID:12532467)
• High activity CYP3A4, but not CYP3A5, which primarily metabolizes testosterone, showed a striking association with the onset of puberty. (PMID:12692107)
• C/EBP alpha and HNF-3 gamma cooperatively regulate CYP3A4 expression in hepatic cells by a mechanism that probably involves chromatin remodeling. (PMID:12695546)
• Down-regulation of cytochrome P450 CYP3A4 is associated with breast cancer CYP3A4 (PMID:12738724)
• “… enzymatic activity of CYP3A4 contributes to many adverse drug-drug interactions.” “…results suggest that human CYP3A4 promoter functions in transgenic mice and this in vivo model can be useful to study transcriptional regulation of this gene” (PMID:12867495)
• Incubation of racemic and nonracemic methadone with CYP3A4 revealed no stereoselectivity for the transformation to EDDP, whereas no EDDP formation was observed with CYP1A2. (PMID:12900870)
• A stereoselectivity in the formation of 2’-hydroxymethaqualone and 2-hydroxymethaqualone from methaqualone was observed in urine and also in vitro using human liver microsomes and preparations containing the cytochrome P450 enzyme (CYP) CYP3A4 only. (PMID:12900872)
• The CYP3A4*1B allele is associated with small cell lung cancers (PMID:14515059)
• increased expression of CYP3A4 is associated with breast tumour (PMID:14643022)
• inherited mutations in the CYP3A4 gene proximal promoter region could cause significant up-regulation of in vitro transcriptional activation by CYP3A4 xenobiotic inducers (PMID:14660173)
• role in detoxification of lithocholic acid (PMID:14681232)
• The catalytic activity of testosterone 6 beta-hydroxylation, membrane binding, and membrane insertion of CYP3A4 increase as a function of anionic phospholipid concentration. (PMID:14690448)
• A novel enhancer of the CYP3A4 gene is identified, referred to as CLEM4, that confers the constitutive activation of CYP3A4 gene in the liver. (PMID:14742674)
• three crystal structures of CYP3A4: unliganded, bound to the inhibitor metyrapone, and bound to the substrate progesterone (PMID:15256616)
• cyp3A4 X-ray crystallographic structure, to 2.05-A resolution (PMID:15258162)
• “The available data indicate that St. John’s wort is a potent inducer of CYP 3A4…” See page 262. (PMID:15260917)
• cytochrome P4503A4 is 46% homologous with CYP2C5 and they are shown to have active sites which accept the same substrates (PMID:15277015)
• No difference in CYP3A4 activity in kidney transplant patients taking either FK506 or Rapamyicn and healthy controls. (PMID:15307840)
• This protein interacts with viral X protein in vivo by yeast two-hybrid system, and may contribute to the development of hepatocellular carcinoma. (PMID:15334674)
• certain properties of CYP3A4 are masked by expression of the protein in insect cells and reinforce the concept that the enzyme possesses multiple binding domains (PMID:15370963)
• P. 92:“In this study…primary human hepatocytes … were treated with dimethylsulfoxide.” “In our experiments CYP3A4 was induced in a concentration-dependent manner by DMSO.” (PMID:15379787)
• presence of two functional FXR recognition sites located in a 345-bp element within the 5’-flanking region of CYP3A4 (PMID:15454728)
• results present a new insight into the individualized CYP3A4-dependent pharmacotherapy and the importance of expression imbalance to human phenotypic diversity (PMID:15459178)
• found a significant increase in the frequency of rearrangements during chemotherapy only in patients homozygous for the wild type CYP3A4*1A allele, providing a direct link between CYP3A4 genotype and susceptibility to drug genotoxicity (PMID:15475069)
• CYP3A4 is both a 24- and 25-hydroxylase for vitamin D(2), 1 alpha OHD(2), and 1 alpha OHD(3). (PMID:15546903)

Cross-species orthologs

20 orthologs

Organism	Symbol	Gene ID
danio_rerio	cyp3c1	ENSDARG00000015575
danio_rerio	cyp3c3	ENSDARG00000037873
danio_rerio	cyp3c2	ENSDARG00000037874
danio_rerio	cyp3c4	ENSDARG00000070021
danio_rerio	cyp3a65	ENSDARG00000103295
mus_musculus	Cyp3a25	ENSMUSG00000029630
mus_musculus	Cyp3a13	ENSMUSG00000029727
mus_musculus	Cyp3a16	ENSMUSG00000038656
mus_musculus	Cyp3a44	ENSMUSG00000054417
mus_musculus	Cyp3a11	ENSMUSG00000056035
mus_musculus	Cyp3a59	ENSMUSG00000061292
mus_musculus	Cyp3a57	ENSMUSG00000070419
mus_musculus	Cyp3a41a	ENSMUSG00000075551
mus_musculus	Cyp3a41b	ENSMUSG00000075552
rattus_norvegicus	Cyp3a18	ENSRNOG00000000969
rattus_norvegicus	Cyp3a73	ENSRNOG00000000978
rattus_norvegicus	Cyp3a62	ENSRNOG00000001379
rattus_norvegicus	Cyp3a23-3a1	ENSRNOG00000032560
rattus_norvegicus	Cyp3a9	ENSRNOG00000046643
rattus_norvegicus	Cyp3a23-3a1	ENSRNOG00000067532

Paralogs (3): CYP3A43 (ENSG00000021461), CYP3A5 (ENSG00000106258), CYP3A7 (ENSG00000160870)

Protein

Protein identifiers

Cytochrome P450 3A4 — P08684 (reviewed: P08684)

Alternative names: 1,4-cineole 2-exo-monooxygenase, 1,8-cineole 2-exo-monooxygenase, Albendazole monooxygenase (sulfoxide-forming), Albendazole sulfoxidase, CYPIIIA3, CYPIIIA4, Cholesterol 25-hydroxylase, Cytochrome P450 3A3, Cytochrome P450 HLp, Cytochrome P450 NF-25, Cytochrome P450-PCN1, Nifedipine oxidase, Quinine 3-monooxygenase

All UniProt accessions (6): P08684, A0A494C0W7, A0A499FJM4, C9JBD2, E7EVM8, Q6GRK0

UniProt curated annotations — full annotation on UniProt →

Function. A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids. 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 hydroxylation of carbon-hydrogen bonds. Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position. Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone. Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones. Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis. Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond. Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling. Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance. Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole. Hydroxylates antimalarial drug quinine. Acts as a 1,4-cineole 2-exo-monooxygenase. Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)).

Subunit / interactions. Interacts with PGRMC1; the interaction requires PGRMC1 homodimerization.

Subcellular location. Endoplasmic reticulum membrane. Microsome membrane.

Tissue specificity. Expressed in prostate and liver. According to some authors, it is not expressed in brain. According to others, weak levels of expression are measured in some brain locations. Also expressed in epithelium of the small intestine and large intestine, bile duct, nasal mucosa, kidney, adrenal cortex, epithelium of the gastric mucosa with intestinal metaplasia, gallbladder, intercalated ducts of the pancreas, chief cells of the parathyroid and the corpus luteum of the ovary (at protein level).

Post-translational modifications. Polyubiquitinated in the presence of AMFR and UBE2G1 and also STUB1/CHIP and UBE2D1 (in vitro).

Disease relevance. Vitamin D-dependent rickets 3 (VDDR3) [MIM:619073] An autosomal dominant disorder of vitamin D metabolism resulting in early-onset rickets, reduced serum levels of the vitamin D metabolites 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, and deficient responsiveness to parent and activated forms of vitamin D. The gene represented in this entry is involved in disease pathogenesis.

Activity regulation. Activated by cytochrome b5.

Induction. By drugs, such as rifampicin.

Pathway. Steroid hormone biosynthesis. Cofactor metabolism; retinol metabolism. Steroid metabolism; cholesterol metabolism. Lipid metabolism; fatty acid metabolism.

Miscellaneous. Chimeric transcripts, characterized by CYP3A43 exon 1 joined at canonical splice sites to distinct sets of CYP3A4 exons, have been detected. All are possibly produced by trans-splicing. The chimeric transcripts exist in 3 different combinations: CYP3A43 exon 1 joined in frame to CYP3A4 exons 2-13, CYP3A43 exon 1 joined in frame to CYP3A4 exons 4-13 and CYP3A43 exon 1 joined in frame to CYP3A4 exon 7-13. The longest chimeric isoform (CYP3A43 exon 1 joined to CYP3A4 exons 2-13) exhibits 6-beta-hydroxylase activity, while a shorter isoform (CYP3A43 exon 1 joined to CYP3A4 exons 4-13) does not. All chimeric transcripts are expressed at very low levels in the liver.

Similarity. Belongs to the cytochrome P450 family.

RefSeq proteins (2): NP_001189784, NP_059488* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001128	Cyt_P450	Family
IPR002402	Cyt_P450_E_grp-II	Family
IPR008072	Cyt_P450_E_CYP3A	Family
IPR017972	Cyt_P450_CS	Conserved_site
IPR036396	Cyt_P450_sf	Homologous_superfamily
IPR050705	Cytochrome_P450_3A	Family

Pfam: PF00067

Enzyme classification (BRENDA):

• EC 1.14.14.55 — quinine 3-monooxygenase (BRENDA: 5 organisms, 7 substrates, 62 inhibitors, 38 Km, 2 kcat entries)
• EC 1.14.14.73 — albendazole monooxygenase (sulfoxide-forming) (BRENDA: 5 organisms, 12 substrates, 8 inhibitors, 0 Km, 0 kcat entries)
• EC 1.14.99.38 — cholesterol 25-monooxygenase (BRENDA: 12 organisms, 12 substrates, 2 inhibitors, 0 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

1 substrates with measured Km, best-characterized 1. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
QUININE	0.0008–0.328	35

Catalyzed reactions (Rhea), 12 shown:

• an organic molecule + reduced [NADPH–hemoprotein reductase] + O2 = an alcohol + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:17149)
• quinine + reduced [NADPH–hemoprotein reductase] + O2 = 3-hydroxyquinine + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:20149)
• 1,8-cineole + reduced [NADPH–hemoprotein reductase] + O2 = 2-exo-hydroxy-1,8-cineole + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:32895)
• (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)
• all-trans-retinol + reduced [NADPH–hemoprotein reductase] + O2 = all-trans-retinal + oxidized [NADPH–hemoprotein reductase] + 2 H2O + H(+) (RHEA:42092)
• cholesterol + reduced [NADPH–hemoprotein reductase] + O2 = 4beta-hydroxycholesterol + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:46128)
• cholesterol + reduced [NADPH–hemoprotein reductase] + O2 = (22R)-hydroxycholesterol + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:46140)
• cholesterol + reduced [NADPH–hemoprotein reductase] + O2 = (24R)-hydroxycholesterol + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:46144)
• testosterone + reduced [NADPH–hemoprotein reductase] + O2 = 6beta,17beta-dihydroxyandrost-4-en-3-one + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:46296)
• estrone + reduced [NADPH–hemoprotein reductase] + O2 = 16alpha-hydroxyestrone + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:47204)
• 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)

UniProt features (91 total): helix 28, sequence variant 22, strand 16, sequence conflict 13, turn 8, initiator methionine 1, chain 1, transmembrane region 1, binding site 1

Structure

Experimental structures (PDB)

122 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
5VCC	X-RAY DIFFRACTION	1.7
9YK4	X-RAY DIFFRACTION	1.78
6MA8	X-RAY DIFFRACTION	1.83
4D6Z	X-RAY DIFFRACTION	1.93
5VCD	X-RAY DIFFRACTION	1.95
3NXU	X-RAY DIFFRACTION	2
1TQN	X-RAY DIFFRACTION	2.05
8EXB	X-RAY DIFFRACTION	2.05
8SO1	X-RAY DIFFRACTION	2.05
6MA7	X-RAY DIFFRACTION	2.09
8EWN	X-RAY DIFFRACTION	2.1
3UA1	X-RAY DIFFRACTION	2.15
6DAA	X-RAY DIFFRACTION	2.15
8EWS	X-RAY DIFFRACTION	2.15
8SO2	X-RAY DIFFRACTION	2.15
6MA6	X-RAY DIFFRACTION	2.18
5VCE	X-RAY DIFFRACTION	2.2
5VCG	X-RAY DIFFRACTION	2.2
8EWD	X-RAY DIFFRACTION	2.2
8EWR	X-RAY DIFFRACTION	2.2
6OOB	X-RAY DIFFRACTION	2.2
6BCZ	X-RAY DIFFRACTION	2.23
3TJS	X-RAY DIFFRACTION	2.25
4D75	X-RAY DIFFRACTION	2.25
6BDH	X-RAY DIFFRACTION	2.25
6DA5	X-RAY DIFFRACTION	2.25
6OO9	X-RAY DIFFRACTION	2.25
7UFB	X-RAY DIFFRACTION	2.25
8EWQ	X-RAY DIFFRACTION	2.25
9PLK	X-RAY DIFFRACTION	2.25

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P08684-F1	92.62	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): 442 (axial binding residue)

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-211945	Phase I - Functionalization of compounds
R-HSA-211981	Xenobiotics
R-HSA-5423646	Aflatoxin activation and detoxification
R-HSA-9027307	Biosynthesis of maresin-like SPMs
R-HSA-9749641	Aspirin ADME
R-HSA-9754706	Atorvastatin ADME
R-HSA-9757110	Prednisone ADME

MSigDB gene sets: 244 (showing top): GOBP_LIPID_MODIFICATION, MODULE_93, REACTOME_BIOLOGICAL_OXIDATIONS, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, GOBP_POLYOL_METABOLIC_PROCESS, GOBP_OXIDATIVE_DEMETHYLATION, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_LONG_CHAIN_FATTY_ACID_METABOLIC_PROCESS, SAENZ_DETOX_PATHWAY_AND_CARCINOGENESIS_DN, GOBP_RETINOL_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_DEMETHYLATION, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS

GO Biological Process (21): lipid hydroxylation (GO:0002933), lipid metabolic process (GO:0006629), steroid catabolic process (GO:0006706), xenobiotic metabolic process (GO:0006805), steroid metabolic process (GO:0008202), cholesterol metabolic process (GO:0008203), androgen metabolic process (GO:0008209), estrogen metabolic process (GO:0008210), alkaloid catabolic process (GO:0009822), monoterpenoid metabolic process (GO:0016098), xenobiotic catabolic process (GO:0042178), vitamin D metabolic process (GO:0042359), vitamin D catabolic process (GO:0042369), retinol metabolic process (GO:0042572), retinoic acid metabolic process (GO:0042573), long-chain fatty acid biosynthetic process (GO:0042759), aflatoxin metabolic process (GO:0046222), oxidative demethylation (GO:0070989), fatty acid metabolic process (GO:0006631), steroid biosynthetic process (GO:0006694), calcitriol biosynthetic process from calciol (GO:0036378)

GO Molecular Function (25): monooxygenase activity (GO:0004497), steroid binding (GO:0005496), iron ion binding (GO:0005506), steroid hydroxylase activity (GO:0008395), retinoic acid 4-hydroxylase activity (GO:0008401), oxidoreductase activity (GO:0016491), oxygen binding (GO:0019825), enzyme binding (GO:0019899), heme binding (GO:0020037), vitamin D 25-hydroxylase activity (GO:0030343), caffeine oxidase activity (GO:0034875), quinine 3-monooxygenase activity (GO:0050591), testosterone 6-beta-hydroxylase activity (GO:0050649), 1-alpha,25-dihydroxyvitamin D3 23-hydroxylase activity (GO:0062181), anandamide 8,9 epoxidase activity (GO:0062187), anandamide 11,12 epoxidase activity (GO:0062188), anandamide 14,15 epoxidase activity (GO:0062189), vitamin D 24-hydroxylase activity (GO:0070576), estrogen 16-alpha-hydroxylase activity (GO:0101020), estrogen 2-hydroxylase activity (GO:0101021), 1,8-cineole 2-exo-monooxygenase activity (GO:0102320), protein binding (GO:0005515), oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen (GO:0016705), 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), metal ion binding (GO:0046872)

GO Cellular Component (5): cytoplasm (GO:0005737), endoplasmic reticulum membrane (GO:0005789), intracellular membrane-bounded organelle (GO:0043231), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Drug ADME	3
Biological oxidations	2
Cytochrome P450 - arranged by substrate type	1
Biosynthesis of maresins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
steroid metabolic process	5
steroid hydroxylase activity	5
hormone metabolic process	4
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	3
anandamide epoxidase activity	3
lipid metabolic process	2
catabolic process	2
retinoid metabolic process	2
monocarboxylic acid metabolic process	2
monooxygenase activity	2
intracellular anatomical structure	2
cellular anatomical structure	2
lipid modification	1
primary metabolic process	1
lipid catabolic process	1
metabolic process	1
cellular response to xenobiotic stimulus	1
sterol metabolic process	1
secondary alcohol metabolic process	1
alkaloid metabolic process	1
terpenoid metabolic process	1
xenobiotic metabolic process	1
steroid catabolic process	1
vitamin D metabolic process	1
fat-soluble vitamin catabolic process	1
primary alcohol metabolic process	1
olefinic compound metabolic process	1
long-chain fatty acid metabolic process	1
fatty acid biosynthetic process	1
mycotoxin metabolic process	1
demethylation	1
lipid biosynthetic process	1
oxidoreductase activity	1
lipid binding	1
transition metal ion binding	1
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	1
catalytic activity	1
small molecule binding	1
protein binding	1
tetrapyrrole binding	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

15 interactions, top by confidence:

A	B	Type	Score
	CYP3A4	psi-mi:“MI:0407”(direct interaction)	0.560
CYP3A4	FANCG	psi-mi:“MI:0915”(physical association)	0.560
CYP3A4	LIAT1	psi-mi:“MI:0915”(physical association)	0.560
CYP3A4	PGRMC1	psi-mi:“MI:0915”(physical association)	0.460
CYP3A4	PGRMC1	psi-mi:“MI:0403”(colocalization)	0.460
CYP3A5	CYP3A4	psi-mi:“MI:0915”(physical association)	0.400
GK	CYP3A4	psi-mi:“MI:0915”(physical association)	0.370
UGT2B7	ACTN4	psi-mi:“MI:0914”(association)	0.350

BioGRID (31): CYP3A4 (Biochemical Activity), CYP3A4 (Biochemical Activity), CYP3A4 (Biochemical Activity), CYP3A4 (Biochemical Activity), CYP3A4 (Affinity Capture-MS), AMFR (Affinity Capture-MS), UBE2G1 (Affinity Capture-MS), UBE2D1 (Affinity Capture-MS), STUB1 (Affinity Capture-MS), HSPA8 (Affinity Capture-MS), CYP3A4 (Affinity Capture-Western), CYP3A4 (Far Western), CYP3A4 (Reconstituted Complex), UGT2B7 (Affinity Capture-Western), CYP3A4 (Affinity Capture-Western)

ESM2 similar proteins: A2A974, F1Q8C3, H1A988, O18993, O35728, O88833, P00186, P04799, P08516, P08684, P13584, P14579, P14581, P15128, P15129, P20815, P20816, P20817, P24453, P24462, P24463, P24464, P33268, P33274, P51869, P51871, P78329, P79102, P79401, P98187, Q00557, Q08477, Q29496, Q3MID2, Q64391, Q64462, Q64464, Q6A152, Q6NT55, Q86W10

Diamond homologs: A0A0C2W6G6, A0A1L9WQK2, A0A1V0QSE7, A0A2H3CSA7, A0A2H3CZX2, A0A3G9HRC2, A0A3S5HYN5, A0A8K1AW54, A2A974, A2RRT9, A8NCK6, B0XZV0, B8QHP5, F1SY62, F1SY74, F1SYB6, F1SYH7, F2K081, F2ZAF9, I1RE80, I1S2J5, I3PLR1, L7X3S1, O08336, O17624, O18993, O43174, O44221, O48786, O49396, O55127, O70537, O88833, P05183, P08684, P0DKI7, P0DOX0, P11372, P11707, P13584

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
DBP	“up-regulates quantity by expression”	CYP3A4	“transcriptional regulation”
NFIL3	“down-regulates quantity by repression”	CYP3A4	“transcriptional regulation”
NR1I2	“up-regulates quantity by expression”	CYP3A4	“transcriptional regulation”
VDR	“up-regulates quantity by expression”	CYP3A4	“transcriptional regulation”
ritonavir	“down-regulates activity”	CYP3A4	“chemical inhibition”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	20
Likely benign	7
Benign	3

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
4082122	NM_017460.6(CYP3A4):c.1095ATT[1] (p.Leu366del)	Pathogenic
545583	GRCh37/hg19 7q21.2-22.1(chr7:92445452-99686985)x1	Pathogenic
982369	NM_017460.6(CYP3A4):c.902T>C (p.Ile301Thr)	Pathogenic

SpliceAI

1499 predictions. Top by Δscore:

Variant	Effect	Δscore
7:99760991:C:CT	acceptor_gain	1.0000
7:99763851:TCAC:T	donor_loss	1.0000
7:99763852:CACC:C	donor_loss	1.0000
7:99763853:A:AC	donor_gain	1.0000
7:99763853:ACCTT:A	donor_loss	1.0000
7:99763854:C:CC	donor_gain	1.0000
7:99763854:CCTT:C	donor_gain	1.0000
7:99763854:CCTTA:C	donor_gain	1.0000
7:99763883:T:TA	donor_gain	1.0000
7:99763966:A:T	acceptor_gain	1.0000
7:99764011:CAGAG:C	acceptor_gain	1.0000
7:99764012:AGAG:A	acceptor_gain	1.0000
7:99764013:GAG:G	acceptor_gain	1.0000
7:99764014:AG:A	acceptor_gain	1.0000
7:99764014:AGCTG:A	acceptor_loss	1.0000
7:99764015:GCTGA:G	acceptor_loss	1.0000
7:99764016:C:CC	acceptor_gain	1.0000
7:99764016:CT:C	acceptor_loss	1.0000
7:99764017:T:C	acceptor_loss	1.0000
7:99766444:C:CC	acceptor_gain	1.0000
7:99767127:TTACC:T	donor_loss	1.0000
7:99767129:ACCTT:A	donor_loss	1.0000
7:99767130:C:CA	donor_loss	1.0000
7:99767254:GACTG:G	acceptor_gain	1.0000
7:99767256:CTG:C	acceptor_gain	1.0000
7:99767257:TG:T	acceptor_gain	1.0000
7:99767259:C:CC	acceptor_gain	1.0000
7:99767271:C:CT	acceptor_gain	1.0000
7:99768351:TACTT:T	donor_loss	1.0000
7:99768352:A:AC	donor_gain	1.0000

AlphaMissense

3332 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:99760930:A:C	F435L	0.997
7:99760930:A:T	F435L	0.997
7:99760932:A:G	F435L	0.997
7:99760978:G:C	F419L	0.996
7:99760978:G:T	F419L	0.996
7:99760980:A:G	F419L	0.996
7:99770178:A:G	W126R	0.996
7:99770178:A:T	W126R	0.996
7:99760915:T:A	R440S	0.995
7:99760915:T:G	R440S	0.995
7:99760922:C:T	G438E	0.995
7:99762200:C:G	R365T	0.995
7:99762209:T:A	E362V	0.995
7:99763889:A:G	L331P	0.995
7:99762199:T:A	R365S	0.994
7:99762199:T:G	R365S	0.994
7:99770165:C:G	R130P	0.994
7:99760916:C:G	R440T	0.993
7:99760928:C:T	G436E	0.993
7:99762169:C:A	R375S	0.993
7:99762169:C:G	R375S	0.993
7:99770176:C:A	W126C	0.993
7:99770176:C:G	W126C	0.993
7:99768484:G:C	S180R	0.992
7:99768484:G:T	S180R	0.992
7:99768486:T:G	S180R	0.992
7:99770143:G:C	F137L	0.992
7:99770143:G:T	F137L	0.992
7:99770145:A:G	F137L	0.992
7:99760909:G:C	C442W	0.990

dbSNP variants (sampled 300 via entrez): RS1000025030 (7:99766738 T>G), RS1000383193 (7:99780605 C>A), RS1000775179 (7:99785778 T>C), RS1000961622 (7:99759921 G>A), RS1001242501 (7:99758641 A>C), RS1001309110 (7:99760299 A>C), RS1001693874 (7:99758377 C>A,G), RS1001771604 (7:99771536 A>G,T), RS1001910502 (7:99769630 A>T), RS1001925092 (7:99777863 A>C), RS1001950465 (7:99771023 C>G), RS1002033850 (7:99763620 G>A), RS1002087603 (7:99763361 T>C), RS1002484986 (7:99784700 A>G), RS1002555313 (7:99782648 T>A)

Disease associations

OMIM: gene MIM:124010 | disease phenotypes: MIM:619073, MIM:143890, MIM:183600

GenCC curated gene-disease

Disease	Classification	Inheritance
vitamin D-dependent rickets, type 3	Limited	Autosomal dominant

Mondo (3): vitamin D-dependent rickets, type 3 (MONDO:0033640), familial hypercholesterolemia (MONDO:0005439), split hand-foot malformation 1 (MONDO:0008464)

Orphanet (1): Isolated split hand-split foot malformation (Orphanet:2440)

HPO phenotypes

15 total (15 of 15 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000938	Osteopenia
HP:0001510	Growth delay
HP:0002148	Hypophosphatemia
HP:0002901	Hypocalcemia
HP:0002970	Genu varum
HP:0002979	Bowing of the legs
HP:0003015	Flared metaphysis
HP:0003021	Metaphyseal cupping
HP:0003155	Elevated circulating alkaline phosphatase concentration
HP:0003165	Elevated circulating parathyroid hormone level
HP:0011463	Childhood onset
HP:0012052	Low serum calcitriol
HP:0012053	Decreased circulating calcifediol concentration
HP:0031936	Delayed ability to walk

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST001217_20	Metabolic traits	9.000000e-40
GCST002882_1	Ticagrelor levels in individuals with acute coronary syndromes treated with ticagrelor	1.000000e-14
GCST002925_11	Sex hormone levels	2.000000e-14
GCST002925_12	Sex hormone levels	2.000000e-07
GCST002925_6	Sex hormone levels	6.000000e-14
GCST005144_1	Tacrolimus trough concentration in kidney transplant patients	2.000000e-17
GCST006625_1	Neonatal cytokine/chemokine levels (maternal genetic effect)	3.000000e-08
GCST008758_65	Pre-treatment viral load in HIV-1 infection	3.000000e-18

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0004725	metabolite measurement
EFO:0007007	ticagrelor measurement
EFO:0004730	hormone measurement
EFO:0007001	dehydroepiandrosterone sulphate measurement
EFO:0004908	testosterone measurement
EFO:0008458	tacrolimus measurement
EFO:0004747	protein measurement
EFO:0005939	parental genotype effect measurement
EFO:0009422	CXCL5 measurement
EFO:0010125	viral load

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2111472 (PROTEIN FAMILY), CHEMBL2364675 (PROTEIN FAMILY), CHEMBL340 (SINGLE PROTEIN), CHEMBL4523986 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

695 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,121,420 (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
CHEMBL157101	KETOCONAZOLE	4	75,361
CHEMBL1136	TELITHROMYCIN	4	15,927
CHEMBL160	CYCLOSPORINE	4	168,247
CHEMBL163	RITONAVIR	4	53,773
CHEMBL269732	TACROLIMUS ANHYDROUS	4	95,168
CHEMBL451887	CARFILZOMIB	4	12,508
CHEMBL638	VORICONAZOLE	4	23,088
CHEMBL1008	BEPRIDIL	4	11,776
CHEMBL101	PHENYLBUTAZONE	4	59,455
CHEMBL1014	CANDESARTAN CILEXETIL	4	11,194
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
CHEMBL1042	CHOLECALCIFEROL	4	64,162
CHEMBL1043	DAPSONE	4	64,779
CHEMBL106	FLUCONAZOLE	4	58,942
CHEMBL1068	OXCARBAZEPINE	4	16,118
CHEMBL107	COLCHICINE	4	93,932
CHEMBL1070	NABUMETONE	4
CHEMBL1071	OXAPROZIN	4
CHEMBL1073	GLIPIZIDE	4
CHEMBL1075	MORICIZINE	4
CHEMBL1082607	SALMETEROL XINAFOATE	4
CHEMBL1083993	AMIODARONE HYDROCHLORIDE	4
CHEMBL1089	PHENELZINE	4
CHEMBL1095292	BRETYLIUM TOSYLATE	4
CHEMBL110	BENZNIDAZOLE	4
CHEMBL1108	DROPERIDOL	4

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

PharmGKB clinical annotations

69 annotations.

Variant	Type	Level	Drugs	Phenotypes
CYP3A41, CYP3A417	Metabolism/PK	3	nifedipine
CYP3A41, CYP3A418	Dosage	4	fentanyl	Pain;Postoperative
CYP3A41, CYP3A418, CYP3A420, CYP3A422	Metabolism/PK	2A	tacrolimus	Kidney Transplantation;Laparoscopic sleeve gastrectomy;Liver transplantation;Lung transplantation
CYP3A41, CYP3A420, CYP3A4*22	Metabolism/PK	1A	quetiapine
CYP3A41, CYP3A422	Metabolism/PK	3	exemestane	Breast Neoplasms
CYP3A41, CYP3A422	Metabolism/PK	3	sildenafil	Heart Failure
CYP3A41, CYP3A422	Metabolism/PK	3	lopinavir	HIV infectious disease
CYP3A41, CYP3A422	Toxicity	3	alprazolam	adverse events;Alcohol abuse;Anxiety Disorders
CYP3A41, CYP3A422	Efficacy	3	alprazolam	Alcohol abuse;Anxiety Disorders
CYP3A41, CYP3A422	Metabolism/PK	3	simvastatin	Hypercholesterolemia
CYP3A41, CYP3A422	Metabolism/PK	4	sirolimus
CYP3A41, CYP3A422	Metabolism/PK	4	everolimus	Breast Neoplasms;Kidney Neoplasms;Kidney Transplantation;Neuroendocrine Tumors
CYP3A41, CYP3A42, CYP3A43, CYP3A44, CYP3A45, CYP3A46, CYP3A47, CYP3A48, CYP3A49, CYP3A410, CYP3A411, CYP3A412, CYP3A413, CYP3A414, CYP3A415, CYP3A416, CYP3A417, CYP3A418, CYP3A419, CYP3A420, CYP3A421, CYP3A422, CYP3A423, CYP3A424, CYP3A426, CYP3A428, CYP3A429, CYP3A430, CYP3A431, CYP3A432, CYP3A433, CYP3A434	Metabolism/PK	3	oxycodone
CYP3A41, CYP3A43	Metabolism/PK	3	quetiapine
CYP3A41, CYP3A43, CYP3A420, CYP3A422	Dosage	2A	tacrolimus	Kidney Transplantation;Organ Transplantation
CYP3A41, CYP3A43, CYP3A420, CYP3A422	Metabolism/PK	3	imatinib
CYP3A41, CYP3A43, CYP3A420, CYP3A422	Metabolism/PK	3	fesoterodine
CYP3A41, CYP3A43, CYP3A420, CYP3A422	Metabolism/PK	3	fentanyl
CYP3A41, CYP3A44	Efficacy	3	simvastatin	Hyperlipidemias
CYP3A41, CYP3A48, CYP3A420, CYP3A422	Toxicity	3	paclitaxel	Breast Neoplasms;Ovarian Neoplasms
rs12721627	Dosage	3	paclitaxel	Neoplasms;Non-Small Cell Lung Carcinoma
rs12721627	Other	3	midazolam
rs2242480	Dosage	2A	fentanyl	Pain;Postoperative
rs2242480	Metabolism/PK	3	fentanyl
rs2242480	Dosage	3	sufentanil	Pain
rs2242480	Toxicity	3	sufentanil	Hypoventilation
rs2242480	Efficacy	4	clopidogrel	Coronary Artery Disease
rs2242480	Metabolism/PK	2A	tacrolimus	Kidney Transplantation;Liver transplantation
rs2242480	Toxicity	3	methadone	Heroin Dependence
rs2242480	Metabolism/PK	3	carbamazepine	Epilepsy
rs2242480	Efficacy	3	fentanyl	Pain;Postoperative
rs2242480	Efficacy	3	sufentanil
rs2242480	Metabolism/PK	3	sufentanil
rs2242480	Toxicity	3	tacrolimus	Liver transplantation
rs2242480	Efficacy	3	atorvastatin	Hyperlipidemias
rs2246709	Toxicity	3	methadone	Heroin Dependence
rs2246709	Efficacy	4	amlodipine	Hypertension
rs2740574	Toxicity	3	cyclophosphamide	Breast Neoplasms
rs2740574	Efficacy,Metabolism/PK	3	lumefantrine	Malaria
rs2740574	Toxicity	3	bleomycin;cisplatin;etoposide	Alopecia;Testicular Neoplasms

PharmGKB variants

49 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1851426	CYP3A4		0.00	0
rs2242480	CYP3A4	2A	24.00	13	fentanyl;clopidogrel;sufentanil;tacrolimus;carbamazepine;methadone;atorvastatin
rs2246709	CYP3A4	3	4.50	2	methadone;amlodipine
rs2687116	CYP3A4		0.00	0
rs2740574	CYP3A4	3	4.00	18	efavirenz;lumefantrine;sirolimus;amlodipine;cyclophosphamide;indinavir;cyclosporine;tacrolimus;bleomycin;cisplatin;etoposide;carbamazepine;atorvastatin;simvastatin
rs3735451	CYP3A4	3	4.50	1	methadone
rs4646437	CYP3A4	2A	10.00	4	tacrolimus;cyclosporine;voriconazole;methadone
rs4646438	CYP3A4		0.00	1
rs4646440	CYP3A4	3	4.50	1	methadone
rs4986907	CYP3A4		0.00	1
rs4986908	CYP3A4		0.00	1
rs4986909	CYP3A4		0.00	1
rs4986910	CYP3A4	3	2.75	7	fluvastatin
rs4986913	CYP3A4		0.00	1
rs4986914	CYP3A4		0.00	0
rs4987161	CYP3A4		0.00	2
rs6956344	CYP3A4		0.00	0
rs12333983	CYP3A4		0.00	0
rs12721627	CYP3A4	3	0.00	3	midazolam;paclitaxel
rs12721629	CYP3A4		0.00	1
rs12721634	CYP3A4		0.00	1
rs28371759	CYP3A4	3	1.25	4	cyclosporine
rs35599367	CYP3A4	3	5.88	21	erythromycin;midazolam;cyclosporine;simvastatin;alprazolam
rs55785340	CYP3A4		0.00	1
rs55901263	CYP3A4		0.00	1
rs55951658	CYP3A4		0.00	2
rs56324128	CYP3A4	3	0.00	2	ticagrelor
rs57409622	CYP3A4		0.00	1
rs67666821	CYP3A4		0.00	8
rs67784355	CYP3A4		0.00	1
rs72552798	CYP3A4		0.00	1
rs72552799	CYP3A4		0.00	2
rs113667357	CYP3A4		0.00	1
rs774109750	CYP3A4		0.00	1
rs756833413	CYP3A4		0.00	1
rs368296206	CYP3A4		0.00	1
rs1303250043	CYP3A4		0.00	1
rs778013004	CYP3A4		0.00	1
rs1449865051	CYP3A4		0.00	1
rs570051168	CYP3A4		0.00	1

PharmGKB dosing guidelines

4 guidelines.

Source	Drug	Guideline	Dosing?	Recommendation?
CPIC	atorvastatin;fluvastatin;lovastatin;pitavastatin;pravastatin;rosuvastatin;simvastatin	Annotation of CPIC Guideline for atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin and CYP3A4, CYP3A5, HMGCR
DPWG	paclitaxel	Annotation of DPWG Guideline for paclitaxel and CYP3A4
DPWG	quetiapine	Annotation of DPWG Guideline for quetiapine and CYP3A4	yes	yes
RNPGx	tacrolimus	Annotation of RNPGx Guideline for tacrolimus and CYP3A4, CYP3A5	yes	yes

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — CYP3 family

Most potent curated ligand interactions (13 total), top 13:

Ligand	Action	Affinity	Parameter
troleandomycin	Inhibition	7.8	pKi
TDI-015051	Inhibition	7.7	pIC50
azalanstat		7.55	pKi
ketoconazole	Inhibition	7.0	pKi
ritonavir	Inhibition	7.0	pKi
BMS-536924	Inhibition	6.3	pIC50
verapamil	Inhibition	6.22	pKi
nefazodone	Inhibition	6.0	pKi
compound 1a [PMID: 18573659]	Inhibition	5.72	pIC50
polyphyllin H	Non-competitive	5.62	pKi
voxelotor	Inhibition	4.9	pIC50
efavirenz	Inhibition	4.76	pIC50
AMG-337	Inhibition	4.3	pIC50

Binding affinities (BindingDB)

734 measured of 1134 human assays (1143 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4,5-diphenyl-1H-imidazole	EC50	0.0037 nM
4-[[2-[(3R,5R,6S)-1-[(1S)-2-tert-butylsulfonyl-1-cyclopropylethyl]-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-3-yl]acetyl]amino]-2-methoxybenzoic acid	IC50	0.0503 nM	US-8952036: Benzoic acid derivative MDM2 inhibitor for the treatment of cancer
2-[(3R,5R,6S)-1-[(1S)-2-tert-butylsulfonyl-1-cyclopropylethyl]-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-3-yl]acetic acid	IC50	0.0962 nM	US-8952036: Benzoic acid derivative MDM2 inhibitor for the treatment of cancer
2-[(3R,5R,6S)-1-[(1S)-2-tert-butylsulfonyl-1-cyclopropylethyl]-6-(4-chloro-3-fluorophenyl)-5-(3-chlorophenyl)-3-methyl-2-oxopiperidin-3-yl]acetic acid	IC50	0.102 nM	US-8952036: Benzoic acid derivative MDM2 inhibitor for the treatment of cancer
4-[[2-[(3R,5R,6S)-1-[(1S)-2-tert-butylsulfonyl-1-cyclopropylethyl]-6-(4-chloro-3-fluorophenyl)-5-(3-chlorophenyl)-3-methyl-2-oxopiperidin-3-yl]acetyl]amino]-2-methoxybenzoic acid	IC50	0.33 nM	US-8952036: Benzoic acid derivative MDM2 inhibitor for the treatment of cancer
(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-[(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
(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
(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
(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
10.66	Ki	0.022	nM	CHEMBL1819091
10.59	Ki	0.026	nM	CHEMBL1819089
10.30	IC50	0.0503	nM	CHEMBL3407558
10.02	IC50	0.0962	nM	CHEMBL3125537
9.99	IC50	0.102	nM	CHEMBL3407554
9.52	IC50	0.3	nM	CHEMBL1271703
9.48	IC50	0.33	nM	CHEMBL3407575
9.40	IC50	0.4	nM	CHEMBL4593464
9.40	IC50	0.4	nM	CHEMBL520419
9.30	IC50	0.5	nM	CHEMBL474469
9.30	IC50	0.5	nM	CHEMBL521271
9.30	IC50	0.5	nM	CHEMBL1271544
9.30	IC50	0.5	nM	CHEMBL1271822
9.15	IC50	0.7	nM	CHEMBL480966
9.15	IC50	0.7	nM	CHEMBL482101
9.10	IC50	0.8	nM	CHEMBL506169
9.10	IC50	0.8	nM	CHEMBL1271879
9.05	IC50	0.9	nM	CHEMBL4636136
9.05	IC50	0.9	nM	CHEMBL482088
9.05	IC50	0.9	nM	KETOCONAZOLE
9.00	IC50	1	nM	CHEMBL2338480
9.00	IC50	1	nM	KETOCONAZOLE
9.00	IC50	1	nM	CHEMBL260636
9.00	IC50	1	nM	CHEMBL405895
9.00	IC50	1	nM	CHEMBL5079148
9.00	IC50	1	nM	CHEMBL454467
9.00	IC50	1	nM	CHEMBL519132
9.00	IC50	1	nM	MICONAZOLE
8.92	Ki	1.2	nM	CHEMBL583090
8.90	AC50	1.259	nM	CHEMBL1318754
8.90	AC50	1.259	nM	PHTHALYLSULFATHIAZOLE
8.89	IC50	1.3	nM	CHEMBL482089
8.89	Potency	1.3	nM	CHEMBL1318754
8.89	Potency	1.3	nM	PHTHALYLSULFATHIAZOLE
8.85	IC50	1.4	nM	CHEMBL539650
8.85	IC50	1.4	nM	CHEMBL1272097
8.85	IC50	1.4	nM	CHEMBL1683443
8.82	IC50	1.5	nM	CHEMBL1271821
8.77	IC50	1.7	nM	CHEMBL510298
8.74	IC50	1.83	nM	CHEMBL3236364
8.74	IC50	1.8	nM	CHEMBL505652
8.70	IC50	2	nM	CHEMBL1272046
8.70	IC50	2	nM	CHEMBL1668898
8.64	IC50	2.3	nM	CHEMBL1271880
8.62	IC50	2.4	nM	CHEMBL4593464
8.62	IC50	2.38	nM	KETOCONAZOLE
8.62	IC50	2.4	nM	CHEMBL450610
8.62	IC50	2.4	nM	CHEMBL451331
8.62	Ki	2.4	nM	TELITHROMYCIN
8.59	IC50	2.6	nM	CHEMBL482102

PubChem BioAssay actives

963 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
2-[(tert-butylamino)methyl]-5-[(7-chloroquinolin-4-yl)amino]phenol	346856: Inhibition of human recombinant CYP3A4 using N-N,diethyl-formamide as substrate	ic50	<0.0001	uM
1-(4-butoxyphenyl)imidazole	2022048: Inhibition of CYP3A4 in human liver microsomes using midazolam as substrate in presence of NADPH	ic50	<0.0001	uM
4-[[(2S)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[6-(4-hydroxypiperidin-1-yl)-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one	339683: Inhibition of CYP3A4	ic50	0.0004	uM
4-[[(2S)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-(4-methyl-6-morpholin-4-yl-1H-benzimidazol-2-yl)-1H-pyridin-2-one	339683: Inhibition of CYP3A4	ic50	0.0005	uM
methyl N-[1-[2-[4-[[(2S)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]-2-oxo-1H-pyridin-3-yl]-7-methyl-3H-benzimidazol-5-yl]piperidin-4-yl]carbamate	339683: Inhibition of CYP3A4	ic50	0.0005	uM
4-[[(2S)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[4-methyl-6-[4-[(1S,4R)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]piperidin-1-yl]-1H-benzimidazol-2-yl]-1H-pyridin-2-one	339683: Inhibition of CYP3A4	ic50	0.0005	uM
4-[[(2S)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[6-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one	339683: Inhibition of CYP3A4	ic50	0.0007	uM
N-[1-[2-[4-[[(2S)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]-2-oxo-1H-pyridin-3-yl]-7-methyl-3H-benzimidazol-5-yl]piperidin-4-yl]cyclopropanecarboxamide	339683: Inhibition of CYP3A4	ic50	0.0007	uM
[1-[(3R,5R)-4-(4-chlorophenyl)sulfonyl-5-(cyclopropylmethyl)morpholin-3-yl]cyclopropyl] 3,8-diazabicyclo[3.2.1]octane-3-carboxylate	528184: Inhibition of CYP3A4 after 30 mins	ic50	0.0008	uM
3-[6-[4-(4-acetylpiperazin-1-yl)piperidin-1-yl]-4-methyl-1H-benzimidazol-2-yl]-4-[[(2S)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]-1H-pyridin-2-one	339683: Inhibition of CYP3A4	ic50	0.0008	uM
4-[[(2S)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[6-[4-(2-methoxyethoxy)piperidin-1-yl]-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one	339683: Inhibition of CYP3A4	ic50	0.0009	uM
4-[[(2S)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[6-(4-methoxypiperidin-1-yl)-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one	339683: Inhibition of CYP3A4	ic50	0.0010	uM
3-[6-[4-[bis(2-methoxyethyl)amino]piperidin-1-yl]-4-methyl-1H-benzimidazol-2-yl]-4-[[(2S)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]-1H-pyridin-2-one	339683: Inhibition of CYP3A4	ic50	0.0010	uM
4-[[(2S)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[6-[4-(2-hydroxyethoxy)piperidin-1-yl]-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one	339683: Inhibition of CYP3A4	ic50	0.0013	uM
N-[(2S,4S)-1-[4-(4-fluorophenyl)piperazin-1-yl]sulfonyl-4-(5-fluoropyrimidin-2-yl)pentan-2-yl]-N-hydroxyformamide	578204: Inhibition of CYP3A4	ic50	0.0014	uM
[1-[(3R,5R)-4-(4-chlorophenyl)sulfonyl-5-(cyclopropylmethyl)morpholin-3-yl]cyclopropyl] 4-methyl-3-oxopiperazine-1-carboxylate	528184: Inhibition of CYP3A4 after 30 mins	ic50	0.0014	uM
4-[[(2S)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[6-[4-[4-(cyclopropanecarbonyl)piperazin-1-yl]piperidin-1-yl]-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one	339683: Inhibition of CYP3A4	ic50	0.0017	uM
2-hydroxyethyl 4-[1-[2-[4-[[(2S)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]-2-oxo-1H-pyridin-3-yl]-7-methyl-3H-benzimidazol-5-yl]piperidin-4-yl]piperazine-1-carboxylate	339683: Inhibition of CYP3A4	ic50	0.0018	uM
[1-[(3R,5R)-4-(4-chlorophenyl)sulfonyl-5-(cyclopropylmethyl)morpholin-3-yl]cyclopropyl] (3R,5S)-4-(2-hydroxyethyl)-3,5-dimethylpiperazine-1-carboxylate	528184: Inhibition of CYP3A4 after 30 mins	ic50	0.0020	uM
[1-[(3R,5R)-4-(4-chlorophenyl)sulfonyl-5-(cyclopropylmethyl)morpholin-3-yl]cyclopropyl] 8-(2-hydroxyethyl)-3,8-diazabicyclo[3.2.1]octane-3-carboxylate	528184: Inhibition of CYP3A4 after 30 mins	ic50	0.0023	uM
4-[[(2S)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[4-methyl-6-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]-1H-benzimidazol-2-yl]-1H-pyridin-2-one	339683: Inhibition of CYP3A4	ic50	0.0024	uM
2-methoxyethyl 4-[1-[2-[4-[[(2S)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]-2-oxo-1H-pyridin-3-yl]-7-methyl-3H-benzimidazol-5-yl]piperidin-4-yl]piperazine-1-carboxylate	339683: Inhibition of CYP3A4	ic50	0.0024	uM
4-[[(2S)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[4-methyl-6-[4-(methylamino)piperidin-1-yl]-1H-benzimidazol-2-yl]-1H-pyridin-2-one	339683: Inhibition of CYP3A4	ic50	0.0026	uM
4-[[(2S)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[6-[4-[4-[2-(2-methoxyethoxy)acetyl]piperazin-1-yl]piperidin-1-yl]-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one	339683: Inhibition of CYP3A4	ic50	0.0030	uM
N-(2-aminoethyl)-2,4-dichloro-N-[4-[(3,5-dimethylphenyl)methoxy]phenyl]benzamide;hydrochloride	1435147: Inhibition of human CYP3A4	ic50	0.0030	uM
4-[[(2S)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[6-[4-[(2S,6R)-2,6-dimethylmorpholin-4-yl]piperidin-1-yl]-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one	339683: Inhibition of CYP3A4	ic50	0.0031	uM
[1-[(3R,5R)-4-(4-chlorophenyl)sulfonyl-5-(cyclopropylmethyl)morpholin-3-yl]cyclopropyl] 5-(2-hydroxyethyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate	528184: Inhibition of CYP3A4 after 30 mins	ic50	0.0032	uM
methyl 4-[1-[2-[4-[[(2S)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]-2-oxo-1H-pyridin-3-yl]-7-methyl-3H-benzimidazol-5-yl]piperidin-4-yl]piperazine-1-carboxylate	339683: Inhibition of CYP3A4	ic50	0.0035	uM
4-[[(2S)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[6-[4-(dimethylamino)piperidin-1-yl]-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one	339683: Inhibition of CYP3A4	ic50	0.0039	uM
2-[4-[[6-[2-(dimethylamino)-1-imidazol-1-ylpropyl]naphthalen-2-yl]oxymethyl]phenyl]acetic acid	241338: Selectivity towards cytochrome P450 3A4 enzyme activity	ic50	0.0040	uM
methyl 2-[4-[[6-[2-(dimethylamino)-1-imidazol-1-ylpropyl]naphthalen-2-yl]oxymethyl]phenyl]acetate	241338: Selectivity towards cytochrome P450 3A4 enzyme activity	ic50	0.0040	uM
2-[(2R)-butan-2-yl]-4-[4-[4-[4-[[(2R,4S)-2-(2,4-dichlorophenyl)-2-(1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-1,2,4-triazol-3-one	1213199: Inhibition of CYP3A4 (unknown origin)	ic50	0.0040	uM
2-[(2S)-butan-2-yl]-4-[4-[4-[4-[[(2R,4S)-2-(2,4-dichlorophenyl)-2-(1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-1,2,4-triazol-3-one	1213199: Inhibition of CYP3A4 (unknown origin)	ic50	0.0040	uM
4-[[(2S)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[4-methyl-6-(4-morpholin-4-ylpiperidin-1-yl)-1H-benzimidazol-2-yl]-1H-pyridin-2-one	339683: Inhibition of CYP3A4	ic50	0.0041	uM
4-[[(2S)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[4-methyl-6-(4-pyrrolidin-1-ylpiperidin-1-yl)-1H-benzimidazol-2-yl]-1H-pyridin-2-one	339683: Inhibition of CYP3A4	ic50	0.0045	uM
4-[[(2S)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[6-[4-[4-(2-methoxyacetyl)piperazin-1-yl]piperidin-1-yl]-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one	339683: Inhibition of CYP3A4	ic50	0.0056	uM
1,1,1-trifluoro-4-(5-fluoro-2-methylphenyl)-4-methyl-2-[(5-morpholin-4-yl-1H-pyrrolo[2,3-c]pyridin-2-yl)methyl]pentan-2-ol	1176702: Inhibition of human recombinant CYP3A4 using 7-benzyloxy-4-(trifluoromethyl)-coumarin as substrate after 30 mins by fluorescence assay	ic50	0.0100	uM
methyl 4-[[6-[2-(dimethylamino)-1-imidazol-1-ylpropyl]naphthalen-2-yl]oxymethyl]benzoate	241338: Selectivity towards cytochrome P450 3A4 enzyme activity	ic50	0.0100	uM
N-(2-aminoethyl)-N-[4-[(4-chlorophenyl)methoxy]phenyl]-4-fluoro-2-(trifluoromethyl)benzamide;hydrochloride	1435147: Inhibition of human CYP3A4	ic50	0.0100	uM
(6R)-1-[4-[3-[(2-methoxyphenyl)methoxy]propoxy]phenyl]-6-[[1-(3-methoxypropyl)-3,4-dihydro-2H-quinolin-7-yl]oxymethyl]piperazin-2-one	263882: Inhibition of CYP3A4 using BFC fluorogenic substrate	ic50	0.0120	uM
[1-[(3R,5R)-4-(4-chlorophenyl)sulfonyl-5-propan-2-ylmorpholin-3-yl]cyclopropyl] 4-(hydroxymethyl)piperidine-1-carboxylate	528184: Inhibition of CYP3A4 after 30 mins	ic50	0.0138	uM
6-[[(2R)-1-[4-[3-[(2-methoxyphenyl)methoxy]propoxy]phenyl]-6-oxopiperazin-2-yl]methylsulfanyl]-4-(3-methoxypropyl)-1,4-benzoxazin-3-one	263882: Inhibition of CYP3A4 using BFC fluorogenic substrate	ic50	0.0140	uM
N-(2-aminoethyl)-2,4-dichloro-N-[4-[(4-propan-2-ylphenyl)methoxy]phenyl]benzamide;hydrochloride	1435147: Inhibition of human CYP3A4	ic50	0.0150	uM
2-[(2R)-butan-2-yl]-4-[4-[4-[4-[[(2S,4S)-2-(2,4-dichlorophenyl)-2-(1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-1,2,4-triazol-3-one	1213178: Inhibition of CYP3A4 in human liver microsomes using midazolam as substrates after 5 mins by LC/MS analysis in presence of NADPH	ic50	0.0160	uM
2-[(2S)-butan-2-yl]-4-[4-[4-[4-[[(2S,4S)-2-(2,4-dichlorophenyl)-2-(1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-1,2,4-triazol-3-one	1213178: Inhibition of CYP3A4 in human liver microsomes using midazolam as substrates after 5 mins by LC/MS analysis in presence of NADPH	ic50	0.0170	uM
methyl N-[(2S)-1-[[(2S,4S,5S)-5-[[(2S)-2-(3-benzyl-2-oxoimidazolidin-1-yl)-3,3-dimethylbutanoyl]amino]-4-hydroxy-6-phenyl-1-(4-pyridin-2-ylphenyl)hexan-2-yl]amino]-3,3-dimethyl-1-oxobutan-2-yl]carbamate	415274: Inhibition of CYP3A4 assessed as midazolam 1’- hydroxylation	ki	0.0180	uM
4-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-(6-imidazol-1-yl-4-methyl-1H-benzimidazol-2-yl)-1H-pyridin-2-one	254944: Concentration required to inhibit cytochrome P450 isozyme CYP3A4-BFC in vitro by 50%	ic50	0.0180	uM
4-[[(2S)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[4-methyl-6-[4-[4-(morpholine-4-carbonyl)piperazin-1-yl]piperidin-1-yl]-1H-benzimidazol-2-yl]-1H-pyridin-2-one	339683: Inhibition of CYP3A4	ic50	0.0190	uM
(1S,2S,4R,6R,8S,9S,11S,12S,13R)-6-[4-[(3-aminophenyl)methyl]phenyl]-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-5,7-dioxapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one	1985124: Inhibition of CYP3A4 (unknown origin)	ic50	0.0200	uM
(3R,5S)-N,1-dibenzyl-3,5-dimethyl-3,5-dihydro-2H-pyrido[3,4-e][1,4]diazepine-4-carboxamide	1325737: Inhibition of CYP3A4 (unknown origin)	ic50	0.0230	uM

CTD chemical–gene interactions

1035 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Rifampin	increases hydroxylation, increases response to substance, affects binding, decreases abundance, increases activity (+12 more)	157
Ketoconazole	increases hydrolysis, decreases expression, increases metabolic processing, affects reaction, decreases reaction (+22 more)	92
Midazolam	affects metabolic processing, decreases hydroxylation, increases glucuronidation, decreases abundance, increases expression (+12 more)	52
Phenobarbital	decreases activity, decreases abundance, increases expression, affects reaction, increases reaction (+4 more)	51
Testosterone	increases chemical synthesis, affects hydroxylation, decreases metabolic processing, decreases hydroxylation, increases expression (+9 more)	49
Dexamethasone	increases reaction, decreases reaction, increases expression, affects metabolic processing, decreases abundance (+4 more)	29
Troleandomycin	decreases metabolic processing, increases expression, decreases reaction, increases hydroxylation, increases metabolic processing (+7 more)	21
Aflatoxin B1	increases metabolic processing, increases chemical synthesis, affects expression, increases expression, affects response to substance (+9 more)	21
6 beta-hydroxytestosterone	increases reaction, decreases chemical synthesis, increases oxidation, increases hydroxylation, decreases reaction (+4 more)	19
Nifedipine	affects binding, decreases reaction, increases reaction, affects oxidation, decreases expression (+6 more)	18
Phenytoin	affects cotreatment, affects response to substance, affects reaction, decreases reaction, increases expression (+3 more)	17
Troglitazone	increases response to substance, decreases activity, increases activity, increases expression, decreases abundance (+3 more)	16
Carbamazepine	affects cotreatment, affects metabolic processing, increases chemical synthesis, decreases activity, increases activity (+6 more)	16
Omeprazole	decreases reaction, increases oxidation, increases activity, affects metabolic processing, increases metabolic processing (+2 more)	16
Chlorpyrifos	decreases activity, increases activity, affects cotreatment, increases expression, increases hydroxylation (+5 more)	15
Plant Extracts	decreases activity, decreases expression, increases activity, affects reaction, increases expression (+2 more)	14
Cyclosporine	affects cotreatment, decreases expression, decreases methylation, decreases reaction, increases oxidation (+5 more)	14
1-hydroxymethylmidazolam	increases oxidation, increases reaction, increases glucuronidation, decreases activity, increases metabolic processing (+6 more)	13
Amiodarone	increases response to substance, increases secretion, increases hydroxylation, increases oxidation, decreases ethylation (+7 more)	13
Calcitriol	affects binding, increases activity, affects reaction, increases expression, increases reaction (+1 more)	13
Itraconazole	affects metabolic processing, increases hydroxylation, increases metabolic processing, affects activity, affects binding (+2 more)	13
Acetaminophen	decreases degradation, decreases expression, increases expression, increases reaction, increases response to substance (+5 more)	12
Erythromycin	decreases methylation, increases metabolic processing, decreases reaction, increases hydroxylation, increases oxidation (+3 more)	12
Quercetin	increases reaction, increases activity, increases metabolic processing, decreases reaction, increases degradation (+4 more)	12
bisphenol A	increases expression, increases reaction, increases activity, increases glutathionylation, increases hydroxylation (+5 more)	11
perfluorooctane sulfonic acid	increases expression, decreases reaction, increases oxidation, decreases activity, decreases expression (+1 more)	11
6-(4-chlorophenyl)imidazo(2,1-b)(1,3)thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime	increases reaction, increases activity, increases expression, decreases reaction	11
Clotrimazole	decreases activity, increases activity, decreases reaction, increases oxidation, increases expression (+1 more)	11
Lithocholic Acid	affects binding, increases reaction, increases hydroxylation, increases oxidation, decreases reaction (+6 more)	11
Diclofenac	affects response to substance, increases response to substance, increases abundance, increases hydroxylation, increases metabolic processing (+3 more)	10

ChEMBL screening assays

5927 unique, capped per target: 5828 admet, 97 binding, 1 functional, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1919560	ADMET	Inhibition of CYP3A4/5-mediated testosterone 6beta-hydroxylation in human liver microsomes by LCMS analysis	Novel orally active antimalarial thiazoles. — J Med Chem
CHEMBL6077306	Binding	Time dependent inhibition of CYP3A4/5 (unknown origin) at 30 uM measured after 30 mins relative to control	Discovery of a Novel Mutant-Selective Epidermal Growth Factor Receptor Inhibitor Using an In Silico Enabled Drug Discovery Platform. — J Med Chem
CHEMBL1741324	Functional	PUBCHEM_BIOASSAY: Cytochrome panel assay with activity outcomes. (Class of assay: other) Panel member name: p450-cyp3a4 Compounds with AC50 equal or less than 10 uM are considered active	PubChem BioAssay data set

Cellosaurus cell lines

20 cell lines: 10 spontaneously immortalized cell line, 6 cancer cell line, 4 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_5332	MCL-5	Transformed cell line	Male
CVCL_8560	HepG2-GS-CYP3A4	Cancer cell line	Male
CVCL_B5W4	Hepc/3A4.2-30	Cancer cell line	Male
CVCL_B6AB	HepaRG CYP3A4 KO	Cancer cell line	Female
CVCL_C0V7	HepG2 PXR-CYP3A4 clone 1	Cancer cell line	Male
CVCL_C0V8	HepG2 PXR-CYP3A4 clone 3	Cancer cell line	Male
CVCL_C0V9	HepG2 PXR-CYP3A4 clone 8	Cancer cell line	Male
CVCL_D1GQ	CHO-CPR/CYP3A4 C1	Spontaneously immortalized cell line	Female
CVCL_D1GT	CHO-CYP3A4 C1	Spontaneously immortalized cell line	Female
CVCL_F0FC	V79MZh3A4/hOR-1	Spontaneously immortalized cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00655265	PHASE4	COMPLETED	A Study of the Safety and Efficacy of Patients With Familial Hypercholesterolaemia Taking Colesevelam as add-on Therapy to Their Existing Medication
NCT00916643	PHASE4	COMPLETED	Low-Density Lipoprotein (LDL) Apheresis Using H.E.L.P. Therapy
NCT03331666	PHASE4	TERMINATED	Impact of LDL-cholesterol Lowering on Platelet Activation
NCT05465278	PHASE4	COMPLETED	Alirocumab and Plaque Burden In Familial Hypercholesterolaemia
NCT00355615	PHASE3	COMPLETED	PLUTO: Pediatric Lipid-redUction Trial of rOsuvastatin
NCT00552097	PHASE3	COMPLETED	Effect of Ezetimibe Plus Simvastatin Versus Simvastatin Alone on Atherosclerosis in the Carotid Artery (ENHANCE)(P02578)
NCT00607373	PHASE3	COMPLETED	Study to Assess the Safety and Efficacy of ISIS 301012 (Mipomersen) in Homozygous Familial Hypercholesterolemia
NCT00694109	PHASE3	COMPLETED	An Open-label Extension Study to Assess the Long-term Safety and Efficacy of ISIS 301012 (Mipomersen) in Patients With Familial Hypercholesterolemia or Severe-Hypercholesterolemia
NCT00827606	PHASE3	COMPLETED	Atorvastatin Three Year Pediatric Study
NCT00943306	PHASE3	COMPLETED	Long Term, Follow-on Study of Lomitapide in Patients With Homozygous Familial Hypercholesterolemia
NCT01524289	PHASE3	COMPLETED	Study to Assess the Tolerability and Efficacy of Anacetrapib (MK-0859) Co-Administered With Statin in Participants With Heterozygous Familial Hypercholesterolemia (MK-0859-020)
NCT01813006	PHASE3	COMPLETED	Effect of Omega-3 Fatty Acid on Endothelial Function
NCT01841684	PHASE3	TERMINATED	Efficacy and Tolerability of Anacetrapib Added to Ongoing Lipid-Lowering Therapy in Adult Participants With Homozygous Familial Hypercholesterolemia (HoFH) (MK-0859-042)
NCT02624869	PHASE3	COMPLETED	Safety, Tolerability and Efficacy of Evolocumab (AMG 145) in Children With Inherited Elevated Low-density Lipoprotein Cholesterol (Familial Hypercholesterolemia)
NCT02748057	PHASE3	COMPLETED	A Clinical Trial to Assess the Long Term Safety and Tolerability of MK-0653H in Japanese Participants With Hypercholesterolemia (MK-0653H-833)
NCT03884452	PHASE3	COMPLETED	Ezetimibe (SCH 58235) Taken With Either Atorvastatin or Simvastatin in Participants With Familial Hypercholesterolemia (MK-0653-018)
NCT04798430	PHASE3	ENROLLING_BY_INVITATION	Long-term Efficacy and Safety of OLE LIB003 in HoFH, HeFH, and High-risk CVD Patients Requiring Further LDL-C Reduction
NCT05142722	PHASE3	COMPLETED	Randomized Study to Evaluate the Effect of Obicetrapib on Top of Maximum Tolerated Lipid-Modifying Therapies
NCT05238519	PHASE3	ACTIVE_NOT_RECRUITING	Improved Diagnosis of Familial Hypercholesterolemia Across the Northland (ID-FH)
NCT05425745	PHASE3	COMPLETED	Evaluate the Effect of Obicetrapib in Patients With HeFH on Top of Maximum Tolerated Lipid-Modifying Therapies.
NCT05952856	PHASE3	COMPLETED	A Study of Enlicitide Decanoate (MK-0616 Oral PCSK9 Inhibitor) in Adults With Hypercholesterolemia (MK-0616-013) CORALreef Lipids
NCT05952869	PHASE3	COMPLETED	A Study of Enlicitide Decanoate (MK-0616 Oral PCSK9 Inhibitor) in Adults With Heterozygous Familial Hypercholesterolemia (MK-0616-017/CORALreef HeFH)
NCT06005597	PHASE3	COMPLETED	Study of Obicetrapib & Ezetimibe Fixed Dose Combination on Top of Maximum Tolerated Lipid-Modifying Therapies
NCT00079846	PHASE2	TERMINATED	Implitapide in Patients With Homozygous Familial Hypercholesterolemia (HoFH) on Maximal Concurrent Lipid-Lowering Therapy
NCT00079859	PHASE2	TERMINATED	Implitapide in Patients With Heterozygous Familial Hypercholesterolemia (HeFH) on Maximal Concurrent Lipid-Lowering Therapy
NCT00477594	PHASE2	COMPLETED	Open Label Extension of ISIS 301012 (Mipomersen) to Treat Familial Hypercholesterolemia
NCT00751608	PHASE2	WITHDRAWN	Effect of APL180 on Endothelial Function in Familial Hypercholesterolemia Patients
NCT02597127	PHASE2	COMPLETED	Trial to Evaluate the Effect of ALN-PCSSC Treatment on Low Density Lipoprotein Cholesterol (LDL-C)
NCT03060577	PHASE2	COMPLETED	An Extension Trial of Inclisiran in Participants With Cardiovascular Disease and High Cholesterol
NCT04455581	PHASE2	UNKNOWN	A Study to Determine the Safety, Tolerability, and Efficacy of SHR-1209 in Patients With Familial Hypercholesterolemia
NCT04941599	PHASE2	RECRUITING	2-Hydroxybenzylamine (2-HOBA) to Reduce HDL Modification and Improve HDL Function in Familial Hypercholesterolemia (FH)
NCT05261126	PHASE2	COMPLETED	A Study of the Efficacy and Safety of Enclitide Chloride (MK-0616 Oral PCSK9 Inhibitor) in Adults With Hypercholesterolemia (MK-0616-008)
NCT00004809	PHASE1	COMPLETED	Phase I Study of Ex Vivo Liver-Directed Gene Therapy for Familial Hypercholesterolemia
NCT02709850	PHASE1	COMPLETED	Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IONIS ANGPTL3-LRx in Healthy Volunteers With Elevated Triglycerides and Participants With Familial Hypercholesterolemia
NCT03747224	PHASE1	COMPLETED	Study of ARO-ANG3 in Healthy Volunteers and in Dyslipidemic Patients
NCT05043181	PHASE1	NOT_YET_RECRUITING	Exosome-based Nanoplatform for Ldlr mRNA Delivery in FH
NCT05851066	PHASE1	COMPLETED	A VSA003 Phase 1 Study in Chinese Adult Healthy Volunteers
NCT02048410	PHASE1/PHASE2	COMPLETED	Efficacy of a New Symbiotic Formulation in Children With Familial Hypercholesterolemia
NCT02100839	PHASE1/PHASE2	COMPLETED	Safety Study of AEM-28 to Treat Refractory Hypercholesterolemia
NCT03832985	EARLY_PHASE1	COMPLETED	Pediatric Reporting of Adult-Onset Genomic Results