CYP8B1

Summary

CYP8B1 (cytochrome P450 family 8 subfamily B member 1, HGNC:2653) is a protein-coding gene on chromosome 3p22.1, encoding 7-alpha-hydroxycholest-4-en-3-one 12-alpha-hydroxylase (Q9UNU6). A cytochrome P450 monooxygenase involved in primary bile acid biosynthesis.

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 endoplasmic reticulum membrane protein catalyzes the conversion of 7 alpha-hydroxy-4-cholesten-3-one into 7-alpha,12-alpha-dihydroxy-4-cholesten-3-one. The balance between these two steroids determines the relative amounts of cholic acid and chenodeoxycholic acid both of which are secreted in the bile and affect the solubility of cholesterol. This gene is unique among the cytochrome P450 genes in that it is intronless.

Source: NCBI Gene 1582 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 65 total
• Druggable target: yes — 7 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_004391

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2653
Approved symbol	CYP8B1
Name	cytochrome P450 family 8 subfamily B member 1
Location	3p22.1
Locus type	gene with protein product
Status	Approved
Aliases	CYP12
Ensembl gene	ENSG00000180432
Ensembl biotype	protein_coding
OMIM	602172
Entrez	1582

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000316161, ENST00000437102

RefSeq mRNA: 1 — MANE Select: NM_004391 NM_004391

CCDS: CCDS2707

Canonical transcript exons

ENST00000316161 — 1 exons

Exon	Start	End
ENSE00001235848	42872192	42875879

Expression profiles

Bgee: expression breadth broad, 83 present calls, max score 98.61.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.8673 / max 439.4489, expressed in 17 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
41829	0.4407	14
41832	0.1500	9
41830	0.1483	10
41833	0.0513	8
41831	0.0237	6
41827	0.0225	7
41826	0.0167	6
41828	0.0142	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	98.61	gold quality
liver	UBERON:0002107	97.90	gold quality
kidney epithelium	UBERON:0004819	88.55	silver quality
tibialis anterior	UBERON:0001385	77.89	silver quality
adult mammalian kidney	UBERON:0000082	74.80	gold quality
sural nerve	UBERON:0015488	72.05	gold quality
kidney	UBERON:0002113	71.83	gold quality
ileal mucosa	UBERON:0000331	70.66	silver quality
cardiac muscle of right atrium	UBERON:0003379	68.85	gold quality
left ventricle myocardium	UBERON:0006566	68.60	gold quality
pancreatic ductal cell	CL:0002079	65.98	silver quality
cortex of kidney	UBERON:0001225	61.56	gold quality
skin of hip	UBERON:0001554	58.27	silver quality
colonic epithelium	UBERON:0000397	58.00	gold quality
myocardium	UBERON:0002349	57.96	gold quality
adult organism	UBERON:0007023	56.69	gold quality
tibial nerve	UBERON:0001323	55.78	gold quality
metanephros cortex	UBERON:0010533	55.73	gold quality
oocyte	CL:0000023	54.45	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
metanephros	UBERON:0000081	52.89	gold quality
renal medulla	UBERON:0000362	51.88	silver quality
gall bladder	UBERON:0002110	49.72	gold quality
right coronary artery	UBERON:0001625	49.28	gold quality
quadriceps femoris	UBERON:0001377	48.99	gold quality
cerebellar vermis	UBERON:0004720	48.93	gold quality
stromal cell of endometrium	CL:0002255	48.77	gold quality
left coronary artery	UBERON:0001626	47.84	gold quality
coronary artery	UBERON:0001621	47.52	gold quality
subcutaneous adipose tissue	UBERON:0002190	47.20	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-130473	yes	396.09
E-MTAB-10553	yes	182.04
E-HCAD-9	yes	53.21
E-ANND-3	yes	3.92

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CLOCK, CNBP, HNF4A, JUN, NR0B2, NR1H4, NR1I2, NR5A2, RORA, SREBF1, SREBF2, STAT5B, TCF3

miRNA regulators (miRDB)

118 targeting CYP8B1, 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-656-3P	100.00	72.15	2788
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-6499-3P	99.90	66.38	1212

Literature-anchored findings (GeneRIF, showing 9)

• Cholesterol loading reduces SREBP-1 mRNA expression in addition to reducing functional SREBP-1 protein, and results in decreasing CYP8B1 gene transcription. (PMID:15249218)
• Studies indicate a homogenous pattern for CYP8B1 expression in human liver, which was even rather than zonal. (PMID:15891895)
• T(3) dose-dependently decreased total bile acid formation in parallel with decreased expression of CYP7A1 and CYP8B1 (PMID:16937432)
• Isoflavone-related induction of 12-alpha-hydroxylase (CYP8B1) was studied in vitro and murine in vivo models. (PMID:17585019)
• SNP rs3732860 of CYP8B1 gene is associated with gallstone disease in this Chinese population. (PMID:22093981)
• The single nucleotide polymorphism rs3732860 in the 3’-untranslated region of the CYP8B1 gene is associated with risk of Gallstone Disease in Chinese Han. (PMID:23216301)
• RORalpha is a key regulator of diurnal rhythm and fasting induction of CYP8B1, which regulates bile acid composition and serum and liver cholesterol levels. (PMID:24226095)
• demonstration that CYP8B1 can also convert chenodeoxycholic acid (CDCA) itself to cholic acid (CA) (PMID:30465713)
• Haploinsufficiency of CYP8B1 associates with increased insulin sensitivity in humans. (PMID:36107630)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cyp8b1.1	ENSDARG00000053068
danio_rerio	cyp8b1.2	ENSDARG00000097556
danio_rerio	cyp8b1.3	ENSDARG00000097559
mus_musculus	Cyp8b1	ENSMUSG00000050445
rattus_norvegicus	Cyp8b1	ENSRNOG00000019481

Paralogs (1): PTGIS (ENSG00000124212)

Protein

Protein identifiers

7-alpha-hydroxycholest-4-en-3-one 12-alpha-hydroxylase — Q9UNU6 (reviewed: Q9UNU6)

Alternative names: 7-alpha-hydroxy-4-cholesten-3-one 12-alpha-hydroxylase, CYPVIIIB1, Cytochrome P450 8B1, Sterol 12-alpha-hydroxylase

All UniProt accessions (2): Q9UNU6, C9JFR9

UniProt curated annotations — full annotation on UniProt →

Function. A cytochrome P450 monooxygenase involved in primary bile acid biosynthesis. Catalyzes the 12alpha-hydroxylation of 7alpha-hydroxy-4-cholesten-3-one, an intermediate metabolite in cholic acid biosynthesis. Controls biliary balance of cholic acid and chenodeoxycholic acid, ultimately regulating the intestinal absorption of dietary lipids. 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–hemoprotein reductase).

Subcellular location. Endoplasmic reticulum membrane. Microsome membrane.

Tissue specificity. Liver.

Pathway. Lipid metabolism; bile acid biosynthesis.

Similarity. Belongs to the cytochrome P450 family.

RefSeq proteins (1): NP_004382* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001128	Cyt_P450	Family
IPR002403	Cyt_P450_E_grp-IV	Family
IPR024204	Cyt_P450_CYP7A1-type	Family
IPR030686	Cytochrome_CYP8B1	Family
IPR036396	Cyt_P450_sf	Homologous_superfamily

Pfam: PF00067

Catalyzed reactions (Rhea), 3 shown:

• 5beta-cholestane-3alpha,7alpha-diol + reduced [NADPH–hemoprotein reductase] + O2 = 5beta-cholestane-3alpha,7alpha,12alpha-triol + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:15261)
• 7alpha-hydroxycholest-4-en-3-one + reduced [NADPH–hemoprotein reductase] + O2 = 7alpha,12alpha-dihydroxycholest-4-en-3-one + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:46752)
• chenodeoxycholate + reduced [NADPH–hemoprotein reductase] + O2 = cholate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:65700)

UniProt features (53 total): helix 20, strand 17, sequence conflict 4, turn 4, sequence variant 4, chain 1, transmembrane region 1, binding site 1, modified residue 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
7LYX	X-RAY DIFFRACTION	2.6
8EOH	X-RAY DIFFRACTION	2.65

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UNU6-F1	91.57	0.77

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): 440 (axial binding residue)

Post-translational modifications (1): 326

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-193368	Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol
R-HSA-193775	Synthesis of bile acids and bile salts via 24-hydroxycholesterol
R-HSA-193807	Synthesis of bile acids and bile salts via 27-hydroxycholesterol
R-HSA-211979	Eicosanoids
R-HSA-211994	Sterols are 12-hydroxylated by CYP8B1
R-HSA-2162123	Synthesis of Prostaglandins (PG) and Thromboxanes (TX)

MSigDB gene sets: 147 (showing top): GOBP_DIGESTION, REACTOME_BIOLOGICAL_OXIDATIONS, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, REACTOME_ENDOGENOUS_STEROLS, GOBP_POSITIVE_REGULATION_OF_DIGESTIVE_SYSTEM_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, CAGCTG_AP4_Q5, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_LIPID_DIGESTION, GOBP_BILE_ACID_BIOSYNTHETIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, UEDA_PERIFERAL_CLOCK, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4, GOBP_RESPONSE_TO_STEROL, KEGG_PPAR_SIGNALING_PATHWAY

GO Biological Process (7): steroid biosynthetic process (GO:0006694), bile acid biosynthetic process (GO:0006699), sterol metabolic process (GO:0016125), response to nutrient levels (GO:0031667), positive regulation of intestinal cholesterol absorption (GO:0045797), response to cholesterol (GO:0070723), lipid metabolic process (GO:0006629)

GO Molecular Function (8): iron ion binding (GO:0005506), sterol 12-alpha-hydroxylase activity (GO:0008397), oxygen binding (GO:0019825), heme binding (GO:0020037), monooxygenase activity (GO:0004497), 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 (3): endoplasmic reticulum membrane (GO:0005789), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Synthesis of bile acids and bile salts	3
Cytochrome P450 - arranged by substrate type	1
Endogenous sterols	1
Arachidonate metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
steroid metabolic process	2
oxidoreductase activity	2
lipid biosynthetic process	1
bile acid metabolic process	1
monocarboxylic acid biosynthetic process	1
response to stimulus	1
intestinal cholesterol absorption	1
regulation of intestinal cholesterol absorption	1
positive regulation of intestinal lipid absorption	1
response to sterol	1
response to alcohol	1
primary metabolic process	1
transition metal ion binding	1
steroid hydroxylase activity	1
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen	1
small molecule binding	1
tetrapyrrole binding	1
catalytic activity	1
cation binding	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1976 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CYP8B1	NR0B2	Q15466	954
CYP8B1	NR5A2	O00482	881
CYP8B1	NR1H4	Q96RI1	845
CYP8B1	KLB	Q86Z14	833
CYP8B1	ABCB11	O95342	805
CYP8B1	SLC10A1	Q14973	796
CYP8B1	SLC10A2	Q12908	719
CYP8B1	SLC51B	Q86UW2	718
CYP8B1	BAAT	Q14032	717
CYP8B1	SLC51A	Q86UW1	716
CYP8B1	GPBAR1	Q8TDU6	692
CYP8B1	ABCG5	Q9H222	679
CYP8B1	HNF4A	P41235	673
CYP8B1	HSD3B7	Q9H2F3	656
CYP8B1	NR1I2	O75469	653

IntAct

3 interactions, top by confidence:

A	B	Type	Score
CYP8B1	TACSTD2	psi-mi:“MI:0914”(association)	0.530

BioGRID (9): TACSTD2 (Affinity Capture-MS), HSPA8 (Affinity Capture-MS), HERC3 (Affinity Capture-MS), GNB2 (Affinity Capture-MS), PTP4A2 (Affinity Capture-MS), HERC3 (Affinity Capture-MS), TACSTD2 (Affinity Capture-MS), HSPA8 (Affinity Capture-MS), NPLOC4 (Affinity Capture-MS)

ESM2 similar proteins: B2RXA7, E1BHJ4, F1RE08, G3V7X8, I1GQE7, O02766, O15528, O35084, O35132, O43174, O55127, O88962, O93323, P00191, P03940, P08686, P0DOX0, P12394, P15540, P30437, P51871, P70085, P98187, Q07973, Q08D50, Q09128, Q16678, Q2LA59, Q2LA60, Q2LCM1, Q3MID2, Q4G0S4, Q5VRM7, Q60991, Q64429, Q64441, Q64562, Q64678, Q6EIG3, Q6V0L0

Diamond homologs: A0A0F7TZ11, A0A167LUR6, A0A482NAL3, A0JJT9, J4UJ10, O23051, P18125, P46634, Q0CPG6, Q27519, Q64505, Q7YRB2, Q9UNU6, A0A0A2JY25, A0A0N9HKQ7, A0A2I1CSG1, A0A4V1FW34, A2QK67, B8N8R3, B8NR71, B8NU02, O02766, A0A0E3D8K9, A0A0E3D8P0, A0A0E3D8P5, A0A0F7TN11, A0A0F7TN60, A0A0F7TSZ5, A0A0U4ZPJ7, A0A0U5CJM3, A0A0U5CJT8, A0A140JWT4, A0A140JWT6, A0A1B4XBI1, A0A1E1FFL4, A0A1E1FFN3, A0A1V6PB34, A0A1Y0BRF2, A0A2I1CSH6, A0A2I6PJ12

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	52
Likely benign	7
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

236 predictions. Top by Δscore:

Variant	Effect	Δscore
3:42864464:A:AG	acceptor_gain	0.9700
3:42864465:G:GG	acceptor_gain	0.9700
3:42865631:G:GT	donor_gain	0.9700
3:42864465:GC:G	acceptor_gain	0.9600
3:42864613:G:GT	donor_gain	0.9600
3:42864465:GCA:G	acceptor_gain	0.9500
3:42865634:G:GT	donor_gain	0.9500
3:42864465:GCAC:G	acceptor_gain	0.9400
3:42864614:A:T	donor_gain	0.9200
3:42864461:CGCA:C	acceptor_loss	0.9100
3:42864464:AG:A	acceptor_loss	0.9100
3:42864465:G:A	acceptor_loss	0.9100
3:42864465:GCACT:G	acceptor_gain	0.9100
3:42874548:G:A	donor_gain	0.8900
3:42864461:CGCAG:C	acceptor_gain	0.8800
3:42864463:CAGCA:C	acceptor_gain	0.8700
3:42864617:G:GT	donor_gain	0.8700
3:42864463:CAG:C	acceptor_gain	0.8500
3:42864468:C:G	acceptor_gain	0.8400
3:42864464:AGC:A	acceptor_gain	0.8300
3:42864464:AGCAC:A	acceptor_gain	0.8300
3:42864460:CCGCA:C	acceptor_gain	0.8200
3:42864462:GCAG:G	acceptor_gain	0.8200
3:42864465:G:T	acceptor_gain	0.8200
3:42864467:A:AG	acceptor_gain	0.8100
3:42870927:G:GT	donor_gain	0.8100
3:42872524:C:CT	acceptor_gain	0.8100
3:42864461:C:CA	acceptor_gain	0.7900
3:42864464:A:AT	acceptor_loss	0.7900
3:42865652:GCC:G	donor_gain	0.7600

AlphaMissense

3320 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:42874593:G:C	F408L	0.993
3:42874593:G:T	F408L	0.993
3:42874595:A:G	F408L	0.993
3:42874780:T:A	E346V	0.993
3:42875613:G:C	F68L	0.992
3:42875613:G:T	F68L	0.992
3:42875615:A:G	F68L	0.992
3:42874520:A:G	W433R	0.991
3:42874520:A:T	W433R	0.991
3:42875199:G:C	F206L	0.990
3:42875199:G:T	F206L	0.990
3:42875201:A:G	F206L	0.990
3:42874518:C:A	W433C	0.987
3:42874518:C:G	W433C	0.987
3:42875484:A:C	F111L	0.987
3:42875484:A:T	F111L	0.987
3:42875486:A:G	F111L	0.987
3:42874499:A:G	C440R	0.985
3:42874941:G:C	F292L	0.985
3:42874941:G:T	F292L	0.985
3:42874943:A:G	F292L	0.985
3:42874959:G:C	N286K	0.985
3:42874959:G:T	N286K	0.985
3:42874940:A:G	W293R	0.983
3:42874940:A:T	W293R	0.983
3:42874608:G:C	F403L	0.982
3:42874608:G:T	F403L	0.982
3:42874610:A:G	F403L	0.982
3:42874976:A:G	W281R	0.982
3:42874976:A:T	W281R	0.982

dbSNP variants (sampled 300 via entrez): RS1000529136 (3:42872975 G>T), RS1000790413 (3:42873178 G>A), RS1000817378 (3:42873111 A>C), RS1001300866 (3:42873339 ACT>A), RS1001368570 (3:42877705 T>C), RS1002580090 (3:42876406 G>C,T), RS1002987792 (3:42875904 G>A,T), RS1004342875 (3:42877407 A>G), RS1004598733 (3:42873593 T>C), RS1005338692 (3:42871895 T>C), RS1005782738 (3:42872660 G>C), RS1006267901 (3:42872183 G>A), RS1007146719 (3:42876869 T>A), RS1007428881 (3:42873999 G>C), RS1007447820 (3:42875443 G>A)

Disease associations

OMIM: gene MIM:602172 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002595_14	Clozapine-induced agranulocytosis	3.000000e-06
GCST004609_107	Monocyte percentage of white cells	8.000000e-38
GCST004625_65	Monocyte count	4.000000e-65
GCST90002407_45	White blood cell count	2.000000e-24

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007989	monocyte percentage of leukocytes
EFO:0005091	monocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523494 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

7 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 203,630 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL1397	POSACONAZOLE	4	541
CHEMBL157101	KETOCONAZOLE	4	75,361
CHEMBL3989843	TRANYLCYPROMINE	4	70
CHEMBL64391	ITRACONAZOLE	4	606
CHEMBL808	ECONAZOLE	4	24,813
CHEMBL91	MICONAZOLE	4	45,914

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — CYP5, CYP7 and CYP8 families

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

Ligand	Action	Affinity	Parameter
miconazole	Inhibition	6.34	pIC50
econazole	Inhibition	6.1	pIC50
tioconazole	Inhibition	5.4	pIC50

ChEMBL bioactivities

91 potent at pChembl≥5 of 91 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.77	IC50	0.17	nM	CHEMBL4436614
9.70	IC50	0.2	nM	CHEMBL4453090
9.70	IC50	0.2	nM	CHEMBL4469186
9.70	IC50	0.2	nM	CHEMBL4455566
9.70	IC50	0.2	nM	CHEMBL4566069
9.66	IC50	0.22	nM	CHEMBL4445397
9.60	IC50	0.25	nM	CHEMBL4459136
9.60	IC50	0.25	nM	CHEMBL4580955
9.55	IC50	0.28	nM	CHEMBL4452352
9.51	IC50	0.31	nM	CHEMBL4450590
9.49	IC50	0.32	nM	CHEMBL4588702
9.47	IC50	0.34	nM	CHEMBL4452739
9.47	IC50	0.34	nM	CHEMBL4435552
9.46	IC50	0.35	nM	CHEMBL4440278
9.42	IC50	0.38	nM	CHEMBL4515054
9.40	IC50	0.4	nM	CHEMBL4576569
9.40	IC50	0.4	nM	CHEMBL4565048
9.40	IC50	0.4	nM	CHEMBL4462103
9.36	IC50	0.44	nM	CHEMBL4568439
9.34	IC50	0.46	nM	CHEMBL4517730
9.34	IC50	0.46	nM	CHEMBL4461071
9.30	IC50	0.5	nM	CHEMBL4438730
9.24	IC50	0.57	nM	CHEMBL4580260
9.22	IC50	0.6	nM	CHEMBL4538016
9.21	IC50	0.61	nM	CHEMBL4468107
9.18	IC50	0.66	nM	CHEMBL4555467
9.17	IC50	0.67	nM	CHEMBL4548303
9.15	IC50	0.7	nM	CHEMBL4530395
9.15	IC50	0.7	nM	CHEMBL4448749
9.15	IC50	0.7	nM	CHEMBL4554911
9.15	IC50	0.7	nM	CHEMBL4554958
9.10	IC50	0.8	nM	CHEMBL4572213
9.10	IC50	0.8	nM	CHEMBL4439430
9.05	IC50	0.9	nM	CHEMBL4461268
9.00	IC50	1	nM	CHEMBL4474123
9.00	IC50	1	nM	CHEMBL4438423
8.96	IC50	1.1	nM	CHEMBL4515105
8.92	IC50	1.2	nM	CHEMBL4452739
8.92	IC50	1.2	nM	CHEMBL4468368
8.92	IC50	1.2	nM	CHEMBL4519936
8.89	IC50	1.3	nM	CHEMBL4555269
8.85	IC50	1.4	nM	CHEMBL4592478
8.77	IC50	1.7	nM	CHEMBL4520631
8.76	IC50	1.75	nM	CHEMBL4460219
8.46	IC50	3.5	nM	CHEMBL4434819
8.44	IC50	3.6	nM	CHEMBL4474799
8.41	IC50	3.91	nM	CHEMBL4459888
8.35	IC50	4.5	nM	CHEMBL4535204
8.28	IC50	5.29	nM	CHEMBL4438582
8.28	IC50	5.2	nM	CHEMBL4514892

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	affects abundance, affects cotreatment, affects expression, decreases expression	7
Benzo(a)pyrene	increases mutagenesis, affects methylation, affects cotreatment, decreases expression, increases methylation	6
Aflatoxin B1	affects expression, decreases expression	3
Acetaminophen	decreases expression, affects cotreatment	2
Atrazine	affects cotreatment, increases expression	2
Chenodeoxycholic Acid	decreases expression, affects cotreatment	2
Cholic Acids	affects cotreatment, affects expression, affects abundance, decreases expression	2
Deoxycholic Acid	decreases expression, affects cotreatment	2
Valproic Acid	decreases expression	2
OTX015	decreases expression	1
mivebresib	decreases expression	1
methyleugenol	decreases expression	1
6-hydroxy-5-((p- sulfophenyl)azo)-2-naphthalenesulfonic acid disodium salt	affects cotreatment, decreases expression	1
benzo(b)fluoranthene	affects cotreatment, decreases expression	1
senecionine	decreases expression	1
senkirkine	decreases expression	1
heliotrine	decreases expression	1
sulforaphane	decreases expression	1
sodium arsenite	decreases expression	1
pregna-4,17-diene-3,16-dione	decreases expression, decreases reaction	1
beta-hexachlorocyclohexane	increases expression	1
benz(a)anthracene	decreases expression, affects cotreatment	1
chrysene	affects cotreatment, decreases expression	1
propiconazole	decreases expression	1
nefazodone	affects cotreatment, decreases expression	1
fipronil	affects cotreatment, decreases expression	1
tebuconazole	decreases expression	1
glyceryl 2-arachidonate	decreases reaction, increases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
obeticholic acid	increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4418432	Binding	Inhibition of CYP8B1 in human liver microsomes using D7-7alpha-hydroxy-4-cholesten-3-one as substrate preincubated for 20 mins followed by substrate addition in presence of NADPH by UPLC-ESI-MS/MS analysis	Cyp8b1 and uses thereof in therapeutic and diagnostic methods

Clinical trials (associated diseases)

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