CYP2B6

Summary

CYP2B6 (cytochrome P450 family 2 subfamily B member 6, HGNC:2615) is a protein-coding gene on chromosome 19q13.2, encoding Cytochrome P450 2B6 (P20813). A cytochrome P450 monooxygenase involved in the metabolism of endocannabinoids and steroids.

This gene, CYP2B6, encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and its expression is induced by phenobarbital. The enzyme is known to metabolize some xenobiotics, such as the anti-cancer drugs cyclophosphamide and ifosphamide. Transcript variants for this gene have been described; however, it has not been resolved whether these transcripts are in fact produced by this gene or by a closely related pseudogene, CYP2B7. Both the gene and the pseudogene are located in the middle of a CYP2A pseudogene found in a large cluster of cytochrome P450 genes from the CYP2A, CYP2B and CYP2F subfamilies on chromosome 19q.

Source: NCBI Gene 1555 — RefSeq curated summary.

At a glance

• GWAS associations: 20
• Clinical variants (ClinVar): 112 total
• Druggable target: yes — 28 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000767

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2615
Approved symbol	CYP2B6
Name	cytochrome P450 family 2 subfamily B member 6
Location	19q13.2
Locus type	gene with protein product
Status	Approved
Aliases	CPB6, CYPIIB6
Ensembl gene	ENSG00000197408
Ensembl biotype	protein_coding
OMIM	123930
Entrez	1555

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000324071, ENST00000593831, ENST00000594187, ENST00000597612, ENST00000598834, ENST00000863357, ENST00000863358

RefSeq mRNA: 1 — MANE Select: NM_000767 NM_000767

CCDS: CCDS12570

Canonical transcript exons

ENST00000324071 — 9 exons

Exon	Start	End
ENSE00001114718	41016646	41018398
ENSE00001114738	40991282	40991476
ENSE00002488696	41009994	41010135
ENSE00002507880	41012674	41012815
ENSE00002519851	41009219	41009395
ENSE00003472814	41004001	41004163
ENSE00003580431	41012298	41012485
ENSE00003613843	41006905	41007065
ENSE00003658654	41004297	41004446

Expression profiles

Bgee: expression breadth ubiquitous, 106 present calls, max score 96.90.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.9449 / max 895.7652, expressed in 23 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
175918	0.7942	15
175917	0.0921	6
175919	0.0414	4
208817	0.0100	5
175920	0.0071	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	96.90	gold quality
liver	UBERON:0002107	95.13	gold quality
buccal mucosa cell	CL:0002336	89.89	gold quality
mucosa of paranasal sinus	UBERON:0005030	86.04	gold quality
nasal cavity epithelium	UBERON:0005384	85.33	gold quality
nephron tubule	UBERON:0001231	82.56	gold quality
tendon of biceps brachii	UBERON:0008188	80.84	gold quality
ileal mucosa	UBERON:0000331	79.98	gold quality
mucosa of transverse colon	UBERON:0004991	79.46	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	77.80	gold quality
metanephric glomerulus	UBERON:0004736	77.56	gold quality
kidney epithelium	UBERON:0004819	76.81	gold quality
renal glomerulus	UBERON:0000074	76.39	gold quality
adult mammalian kidney	UBERON:0000082	74.44	gold quality
jejunal mucosa	UBERON:0000399	74.18	gold quality
small intestine Peyer’s patch	UBERON:0003454	71.45	gold quality
kidney	UBERON:0002113	70.75	gold quality
nasal cavity mucosa	UBERON:0001826	70.74	gold quality
bronchial epithelial cell	CL:0002328	70.11	silver quality
duodenum	UBERON:0002114	69.75	gold quality
small intestine	UBERON:0002108	69.55	gold quality
medial globus pallidus	UBERON:0002477	67.82	silver quality
rectum	UBERON:0001052	66.39	gold quality
transverse colon	UBERON:0001157	66.13	gold quality
cortex of kidney	UBERON:0001225	65.79	gold quality
metanephros	UBERON:0000081	65.35	gold quality
tibialis anterior	UBERON:0001385	62.09	silver quality
gall bladder	UBERON:0002110	61.99	gold quality
hair follicle	UBERON:0002073	61.02	gold quality
diaphragm	UBERON:0001103	60.48	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-100618	yes	129.85
E-ANND-3	yes	4.56

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, AP1, ATF5, CEBPA, CEBPB, CEBPG, CTNNB1, EGR1, ESR1, FOXL2, FOXM1, GABPA, HNF1A, HNF4A, HR, JUN, NCOA1, NCOA3, NR0B1, NR1I2, NR1I3, NR3C1, NR5A1, SFPQ, SP1, STAT5A, TCF3, TP53, UBP1, WT1

miRNA regulators (miRDB)

81 targeting CYP2B6, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-383-3P	99.85	65.84	1359
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-1179	99.71	68.70	1040
HSA-MIR-30B-3P	99.70	65.76	2325

Literature-anchored findings (GeneRIF, showing 40)

• expression in hepatocytes by vitamin D receptor pathway (PMID:11991950)
• substitution of residue 363 in CYP2B6 resulted in significant alterations of the metabolite profile for the side chain hydroxylation of 7-butoxycoumarin (PMID:12490624)
• a novel xenobiotic-responsive enhancer module in the distal region of the CYP2B6 promoter (CYP2B6-XREM) together with the PBREM mediates optimal drug-induced expression of CYP2B6 (PMID:12571232)
• Down-regulation of cytochrome P450 CYP2B6 is associated with breast cancer (PMID:12738724)
• CYP2B6 is highly inducible by known CYP3A4 inducers and suggest that human pregnane X receptor is a major determinant of CYP2B6-inducible expression (PMID:14977870)
• Data show that the mean plasma efavirenz concentration of HIV-1 patients homozygous for CYP2B6 *6/*6 (Q172H and K262R) was significantly higher than that of patients heterozygous for *6 or without alleles *6. (PMID:15194512)
• The two cis-acting elements, the distal PBREM and the proximal OARE, within the chromatin structure are both regulated by CAR in response to okadaic acid and TCPOBOP to maximally induce the CYP2B6 promoter. (PMID:15563456)
• AMPK has a role in the phenobarbital induction of CYP2B gene expression (PMID:15572372)
• CYP2B6 polymorphism has a role in plasma and intracellular concentrations and toxicity of efavirenz and nevirapine in HIV-infected patients (PMID:15864119)
• CYP2B6 genotype influences (S)-methadone and, to a lesser extent, (R)-methadone plasma levels. (PMID:16338275)
• a novel specific CYP2B6 allele in Africans causes impaired metabolism of the HIV drug efavirenz (PMID:16495778)
• CYP2B6 variants, previously shown to affect metabolism of a variety of drugs, occur in West Africa and Papua New Guinea, and there are significant genetic differences at the CYP2B6 locus in these populations (PMID:16506047)
• SMC1 binding represses OARE [OA (okadaic acid) response element] activity and its dissociation allows the recruitment of CAR(constitutive active/androstane receptor) to the OARE, synergizing the expression of the CYP2B6 gene. (PMID:16623664)
• the reliable and quick Pyrosequencing assay affords facilitated future research on the importance of CYP2B6 (PMID:17054410)
• CYP2B6-G516T polymorphisms significantly affect the CL/F rate of EFV in children. (PMID:17356468)
• Significant interethnic differences occur at the CYP2B6 locus, which may influence treatment outcomes with efavirenz. (PMID:17391322)
• Decreased expression of CYP2B6 might play a role in the development of prostate cancer, and be useful as the prognostic predictor for human prostate cancer. (PMID:17455229)
• Results document the spectrum of CYP2B6 allelic variants and genotypes in a southern Chinese population. The 516G > T allele is associated with a defective metabolism of efavirenz (EFV), which therefore may predispose to drug toxicity. (PMID:17465455)
• single nucleotide polymorphisms in the promoter region or introns in the CYP2B6 affect the potency of cyclophosphamide activation to 4-hydroxycyclophosphamide (PMID:17502835)
• CYP2B6 polymorphism markedly influences the metabolism of efavirenz in human liver microsomes and represents a first step toward elucidating the mechanism by which this allele identifies patients exhibiting very high efavirenz plasma concentrations. (PMID:17559344)
• With over 100 described single nucleotide polymorphisms, numerous complex haplotypes and distinct ethnic frequencies, CYP2B6 is one of the most polymorphic CYP genes in humans. (PMID:17638512)
• Results show that 2-phenyl-2-(1-piperidinyl)propane (PPP) is a selective chemical inactivator of CYP2B6 and be used to define the role of CYP2B6 in the metabolism of drugs. (PMID:17682072)
• CYP2B6*29 represents a new mechanism of genetic variation at the CYP2B6 locus, underscoring the highly polymorphic nature of this isoenzyme. (PMID:17885627)
• CYP2B6 genetic variation is associated with the metabolism of nicotine and cotinine among individuals with decreased CYP2A6 activity (PMID:18004205)
• the mechanism of the common *6 allele involves predominantly aberrant splicing, thus leading to reduced functional mRNA, protein, and activity. (PMID:18171905)
• S-bupropion hydroxylation and (S,S)-hydroxybupropion formation clearance may be a useful and improved phenotypic probe for CYP2B6 (PMID:18287571)
• CAR requires early growth response 1 to activate the human cytochrome P450 2B6 gene (PMID:18303024)
• ATF5 is abundant in the liver, activates CYP2B6, and cooperates with the constitutive androstane receptor in sustaining the hepatic-specific expression of this P450 in human hepatocytes and hepatoma cells. (PMID:18332083)
• Mechanisms underlying the differential effects of the K262R mutation of CYP2B6 are reported. (PMID:18621926)
• results indicate that CYP2B6 genotype can to identify efavirenz poor metabolizers in TB/HIV con-infected patients co-treated with rifampin. (PMID:18728241)
• The effect of efavirenz on bupropion hydroxylation as a marker of cytochrome P450 (CYP) 2B6 activity in healthy subjects is reported. (PMID:18989234)
• CYP2B6 G516T polymorphism but not rifampin coadministrtion influences steady-state pharmacokinetics of efavirenz in human immunodeficiency virus-infected patients in South India. (PMID:19124658)
• CYP2B6 G15631T polymorphism is associated with acute leukemia susceptibility. (PMID:19144407)
• Cytochrome P450 2B6 516G–>T is associated with plasma concentrations of nevirapine at both 200 mg twice daily and 400 mg once daily in an ethnically diverse population (PMID:19228205)
• Distribution of functional CYP2B haplotypes among HIV infected African American patients is significant different from that among control subjects. (PMID:19239339)
• Lys262Arg polymorphism of the CYP2B6 gene may be a genetic marker for evaluating the risk of sporadic prostate cancer in native Japanese men (PMID:19425200)
• Patients showing G/T and T/T CYP2B6 polymorphisms exhibited efavirenz clearances that were about 50% and 75% lower than those observed in the patients without these polymorphisms (G/G). (PMID:19433561)
• In microsomal preparations isolated from pediatric livers ranging from 10 weeks gestational age to 17 yrs, percentage of samples with detectable CYP2B6 increases with age from 64% in fetal samples to 95% in samples from donors more than 10 years of age. (PMID:19464434)
• ERG1 may loop the distal enhancer PB responsive enhancer module towards the proximal OA response element KI so that together, CAR and HNF4alpha synergistically activate the CYP2B6 promoter. (PMID:19467232)
• CYP2B6-516G>T polymorphisms significantly affect the drug metabolism of efavirenz in children. (PMID:19474465)

Cross-species orthologs

0 orthologs

Paralogs (15): CYP2W1 (ENSG00000073067), CYP2D6 (ENSG00000100197), CYP2C18 (ENSG00000108242), CYP2E1 (ENSG00000130649), CYP2J2 (ENSG00000134716), CYP2C9 (ENSG00000138109), CYP2C8 (ENSG00000138115), CYP2U1 (ENSG00000155016), CYP2C19 (ENSG00000165841), CYP2S1 (ENSG00000167600), CYP2R1 (ENSG00000186104), CYP2F1 (ENSG00000197446), CYP2A13 (ENSG00000197838), CYP2A7 (ENSG00000198077), CYP2A6 (ENSG00000255974)

Protein

Protein identifiers

Cytochrome P450 2B6 — P20813 (reviewed: P20813)

Alternative names: 1,4-cineole 2-exo-monooxygenase, CYPIIB6, Cytochrome P450 IIB1

All UniProt accessions (3): A0A2R8YFA4, P20813, M0QZJ2

UniProt curated annotations — full annotation on UniProt →

Function. A cytochrome P450 monooxygenase involved in the metabolism of endocannabinoids and steroids. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH–hemoprotein reductase). Catalyzes the epoxidation of double bonds of arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling. Hydroxylates steroid hormones, including testosterone at C-16 and estrogens at C-2. Plays a role in the oxidative metabolism of xenobiotics, including plant lipids and drugs. Acts as a 1,4-cineole 2-exo-monooxygenase. Allele 2B6*9: Has low affinity for anandamide and can only produce 11,12 EpETrE-EAs.

Subcellular location. Endoplasmic reticulum membrane. Microsome membrane.

Tissue specificity. Expressed in liver, lung and heart right ventricle.

Post-translational modifications. Phosphorylation is accompanied by a decrease in enzyme activity.

Induction. By phenobarbital.

Polymorphism. Variability among CYP2B6 alleles may account for differential metabolism of endogenous steroids and endocannabinoids among individuals. For 16-alpha hydroxylation of testosterone, Vmax/Km values between alleles decrease in the following order: 2B61 > 2B66 > 2B69 > 2B74. For 16-beta hydroxylation of testosterone, 2B66 has the highest catalytic efficiency. For anandamide metabolism, 2B66 and 2B69 alleles show significantly lower rates of epoxidation. Genetic variations in CYP2B6 are responsible for poor metabolism of efavirenz and, therefore, susceptibility to efavirenz toxicity in the central nervous system [MIM:614546]. Efavirenz is a non-nucleoside reverse transcriptase inhibitor frequently prescribed with 2 nucleoside reverse transcriptase inhibitors as initial therapy for human immunodeficiency virus (HIV) infection. Up to half of patients treated with efavirenz, experience side effects in the central nervous system, including dizziness, insomnia, impaired concentration, somnolence, and abnormal dreams. Severe depression, aggressive behavior, and paranoid or manic reactions may also occur, depending on efavirenz concentration in the plasma. Patients homozygous for 2B66 have significantly higher plasma efavirenz levels when compared to 2B6*6 heterozygous ones.

Similarity. Belongs to the cytochrome P450 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P20813-1	1	yes
P20813-2	2

RefSeq proteins (1): NP_000758* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001128	Cyt_P450	Family
IPR002401	Cyt_P450_E_grp-I	Family
IPR008068	Cyt_P450_E_grp-I_CYP2B-like	Family
IPR017972	Cyt_P450_CS	Conserved_site
IPR036396	Cyt_P450_sf	Homologous_superfamily
IPR050182	Cytochrome_P450_fam2	Family

Pfam: PF00067

Enzyme classification (BRENDA):

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

Substrate kinetics (BRENDA)

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

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

Catalyzed reactions (Rhea), 8 shown:

• testosterone + reduced [NADPH–hemoprotein reductase] + O2 = 16beta,17beta-dihydroxyandrost-4-en-3-one + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:46304)
• 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)
• 1,4-cineole + reduced [NADPH–hemoprotein reductase] + O2 = 2-exo-hydroxy-1,4-cineole + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:49160)
• N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + reduced [NADPH–hemoprotein reductase] + O2 = N-(8,9-epoxy-5Z,11Z,14Z-eicosatrienoyl)-ethanolamine + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:53140)
• N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + reduced [NADPH–hemoprotein reductase] + O2 = N-(11,12-epoxy-5Z,8Z,14Z-eicosatrienoyl)-ethanolamine + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:53144)
• N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + reduced [NADPH–hemoprotein reductase] + O2 = N-(14,15-epoxy-5Z,8Z,11Z-eicosatrienoyl)-ethanolamine + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:53148)
• testosterone + reduced [NADPH–hemoprotein reductase] + O2 = 16alpha,17beta-dihydroxyandrost-4-en-3-one + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:53196)

UniProt features (66 total): helix 21, sequence variant 19, strand 11, turn 8, sequence conflict 2, splice variant 2, chain 1, binding site 1, modified residue 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
5UFG	X-RAY DIFFRACTION	1.76
5UDA	X-RAY DIFFRACTION	1.93
3IBD	X-RAY DIFFRACTION	2
4I91	X-RAY DIFFRACTION	2
5UAP	X-RAY DIFFRACTION	2.03
3QOA	X-RAY DIFFRACTION	2.1
4RQL	X-RAY DIFFRACTION	2.1
4RRT	X-RAY DIFFRACTION	2.2
4ZV8	X-RAY DIFFRACTION	2.24
5UEC	X-RAY DIFFRACTION	2.27
3QU8	X-RAY DIFFRACTION	2.8
3UA5	X-RAY DIFFRACTION	2.8
5WBG	X-RAY DIFFRACTION	2.99

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P20813-F1	94.25	0.91

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): 436 (axial binding residue)

Post-translational modifications (1): 128

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-211935	Fatty acids
R-HSA-211945	Phase I - Functionalization of compounds
R-HSA-211981	Xenobiotics
R-HSA-211999	CYP2E1 reactions

MSigDB gene sets: 169 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, MODULE_93, MODULE_416, REACTOME_BIOLOGICAL_OXIDATIONS, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, GNF2_HPN, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GOBP_LONG_CHAIN_FATTY_ACID_METABOLIC_PROCESS, SAENZ_DETOX_PATHWAY_AND_CARCINOGENESIS_DN, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_KETONE_METABOLIC_PROCESS, CAIRO_HEPATOBLASTOMA_CLASSES_DN, WIEMANN_TELOMERE_SHORTENING_AND_CHRONIC_LIVER_DAMAGE_UP, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A4

GO Biological Process (7): xenobiotic metabolic process (GO:0006805), steroid metabolic process (GO:0008202), epoxygenase P450 pathway (GO:0019373), xenobiotic catabolic process (GO:0042178), ketone metabolic process (GO:0042180), lipid metabolic process (GO:0006629), small molecule metabolic process (GO:0044281)

GO Molecular Function (14): monooxygenase activity (GO:0004497), iron ion binding (GO:0005506), testosterone 16-alpha-hydroxylase activity (GO:0008390), arachidonate epoxygenase activity (GO:0008392), oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen (GO:0016712), heme binding (GO:0020037), testosterone 16-beta-hydroxylase activity (GO:0062184), anandamide 8,9 epoxidase activity (GO:0062187), anandamide 11,12 epoxidase activity (GO:0062188), anandamide 14,15 epoxidase activity (GO:0062189), estrogen 2-hydroxylase activity (GO:0101021), 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 (4): cytoplasm (GO:0005737), endoplasmic reticulum membrane (GO:0005789), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Cytochrome P450 - arranged by substrate type	2
Biological oxidations	1
Xenobiotics	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
metabolic process	3
steroid hydroxylase activity	3
anandamide epoxidase activity	3
oxidoreductase activity	2
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	2
cellular anatomical structure	2
cellular response to xenobiotic stimulus	1
lipid metabolic process	1
arachidonate metabolic process	1
xenobiotic metabolic process	1
catabolic process	1
primary metabolic process	1
transition metal ion binding	1
arachidonate monooxygenase activity	1
monooxygenase activity	1
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	1
tetrapyrrole binding	1
catalytic activity	1
cation binding	1
intracellular anatomical structure	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1936 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CYP2B6	PPIG	Q13427	964
CYP2B6	POR	P16435	910
CYP2B6	CYB5B	O43169	896
CYP2B6	CYB5A	P00167	893
CYP2B6	NR1I2	O75469	864
CYP2B6	NR1I3	Q14994	840
CYP2B6	UGT1A4	P22310	780
CYP2B6	UGT1A6	P19224	777
CYP2B6	UGT2B7	P16662	775
CYP2B6	UGT1A1	P22309	772
CYP2B6	UGT1A10	Q9HAW8	770
CYP2B6	UGT1A8	Q9HAW9	770
CYP2B6	UGT1A7	Q9HAW7	769
CYP2B6	FDX1	P10109	734
CYP2B6	CXADR	P78310	733

IntAct

6 interactions, top by confidence:

A	B	Type	Score
CYP2B6	HMGB3	psi-mi:“MI:0915”(physical association)	0.400
CYP2B6	DDI2	psi-mi:“MI:0915”(physical association)	0.400
CYP2B6	ATP2B4	psi-mi:“MI:0914”(association)	0.350
RIC8B	GNAS	psi-mi:“MI:0914”(association)	0.350

BioGRID (12): ATP2B3 (Affinity Capture-MS), ATP2B2 (Affinity Capture-MS), ATP2B4 (Affinity Capture-MS), DHRS4 (Affinity Capture-MS), CYP2B6 (Proximity Label-MS), DHRS4 (Affinity Capture-MS), ATP2B3 (Affinity Capture-MS), ATP2B4 (Affinity Capture-MS), ATP2B2 (Affinity Capture-MS), CYP2B6 (Affinity Capture-MS), DDI2 (Affinity Capture-MS), RPS7 (Cross-Linking-MS (XL-MS))

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

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

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
ATF5	“up-regulates quantity by expression”	CYP2B6	“transcriptional regulation”
EGR1	“up-regulates quantity by expression”	CYP2B6	“transcriptional regulation”
NR1I3	“up-regulates quantity by expression”	CYP2B6	“transcriptional regulation”
ritonavir	“up-regulates activity”	CYP2B6	“chemical activation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	74
Likely benign	18
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

1334 predictions. Top by Δscore:

Variant	Effect	Δscore
19:40991475:GG:G	donor_gain	1.0000
19:40991476:GG:G	donor_gain	1.0000
19:41003985:T:TA	acceptor_gain	1.0000
19:41004161:ATGG:A	donor_loss	1.0000
19:41004164:G:GG	donor_gain	1.0000
19:41004164:GT:G	donor_loss	1.0000
19:41004165:T:G	donor_loss	1.0000
19:41004290:A:AG	acceptor_gain	1.0000
19:41004293:CCA:C	acceptor_loss	1.0000
19:41004294:CAG:C	acceptor_loss	1.0000
19:41004295:AGGTG:A	acceptor_loss	1.0000
19:41004296:G:GC	acceptor_loss	1.0000
19:41004296:GGT:G	acceptor_gain	1.0000
19:41004404:G:GT	donor_gain	1.0000
19:41004443:AAGG:A	donor_gain	1.0000
19:41004444:AGG:A	donor_gain	1.0000
19:41004444:AGGGT:A	donor_loss	1.0000
19:41004445:GG:G	donor_gain	1.0000
19:41004445:GGG:G	donor_gain	1.0000
19:41004445:GGGTG:G	donor_loss	1.0000
19:41004446:GG:G	donor_gain	1.0000
19:41004446:GGTG:G	donor_loss	1.0000
19:41004447:G:GG	donor_gain	1.0000
19:41004448:T:A	donor_loss	1.0000
19:41006903:AGG:A	acceptor_gain	1.0000
19:41006904:GGG:G	acceptor_gain	1.0000
19:41006935:A:AG	acceptor_gain	1.0000
19:41006936:G:GG	acceptor_gain	1.0000
19:41007049:GCTCT:G	donor_gain	1.0000
19:41007050:C:G	donor_gain	1.0000

AlphaMissense

3244 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:41012806:T:C	F429L	0.989
19:41012808:C:A	F429L	0.989
19:41012808:C:G	F429L	0.989
19:41012397:A:T	E355V	0.983
19:41012758:T:C	F413L	0.983
19:41012760:T:A	F413L	0.983
19:41012760:T:G	F413L	0.983
19:41012384:G:C	A351P	0.980
19:41012407:A:C	R358S	0.979
19:41012407:A:T	R358S	0.979
19:41004341:T:C	F127L	0.977
19:41004343:C:A	F127L	0.977
19:41004343:C:G	F127L	0.977
19:41012725:T:C	F402L	0.976
19:41012727:T:A	F402L	0.976
19:41012727:T:G	F402L	0.976
19:41012743:T:C	F408L	0.976
19:41012745:C:A	F408L	0.976
19:41012745:C:G	F408L	0.976
19:41004112:T:C	F95L	0.975
19:41004114:C:A	F95L	0.975
19:41004114:C:G	F95L	0.975
19:41012406:G:C	R358T	0.974
19:41004056:T:A	V76D	0.973
19:41016690:T:C	F447L	0.970
19:41016692:C:A	F447L	0.970
19:41016692:C:G	F447L	0.970
19:41004336:G:C	R125P	0.967
19:41004432:T:C	L157P	0.967
19:41010099:G:C	G310R	0.967

dbSNP variants (sampled 300 via entrez): RS1000201388 (19:41009941 G>A), RS1000307838 (19:41009790 A>G), RS1000601124 (19:41010733 T>G), RS1000721026 (19:41015935 A>G), RS1000869816 (19:41001423 G>A), RS1000910952 (19:40996510 A>G,T), RS1001170807 (19:41015002 T>G), RS1001402048 (19:40991913 T>C), RS1001500740 (19:41005896 G>T), RS1001542300 (19:41005652 G>A), RS1001659226 (19:41010276 A>C,G), RS1001990769 (19:41006518 A>T), RS1002266544 (19:41006731 T>C,G), RS1002411041 (19:40996759 C>CA), RS1002468205 (19:41001954 A>T)

Disease associations

OMIM: gene MIM:123930 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): efavirenz central nervous system toxicity, susceptibility to (MONDO:0800431)

Orphanet (0):

HPO phenotypes

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

GWAS associations

20 associations (top):

Study	Trait	p-value
GCST000667_5	Smoking behavior	6.000000e-06
GCST002839_37	Polychlorinated biphenyl levels	3.000000e-08
GCST002839_41	Polychlorinated biphenyl levels	1.000000e-07
GCST002839_57	Polychlorinated biphenyl levels	4.000000e-13
GCST003376_1	Nicotine metabolite ratio	9.000000e-15
GCST003629_12	Nicotine metabolite ratio in current smokers	2.000000e-08
GCST003923_1	DDT metabolite (p,p’-DDE levels)	2.000000e-31
GCST003923_2	DDT metabolite (p,p’-DDE levels)	1.000000e-19
GCST004281_1	Midgestational circulating levels of organochlorine pesticides	8.000000e-11
GCST004285_2	Midgestational circulating levels of PBDEs	8.000000e-06
GCST004285_6	Midgestational circulating levels of PBDEs	2.000000e-08
GCST004285_9	Midgestational circulating levels of PBDEs	4.000000e-06
GCST008444_4	High density lipoprotein cholesterol levels	5.000000e-07
GCST009921_7	Carotid intima media thickness (mean)	1.000000e-10
GCST010867_48	Coronary artery disease	3.000000e-07
GCST011379_11	Cutaneous mastocytosis (childhood)	7.000000e-08
GCST011381_3	Cutaneous mastocytosis	6.000000e-13
GCST011383_3	Mastocytosis	4.000000e-15
GCST011743_66	HDL cholesterol levels in HIV infection	3.000000e-06
GCST012233_1	DDT metabolite (p,p’-DDE levels)	3.000000e-31

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004318	smoking behavior
EFO:0007042	polychlorinated biphenyls measurement
EFO:0007794	nicotine metabolite ratio
EFO:0007886	DDT metabolite measurement
EFO:0007960	organochlorine pesticide measurement
EFO:0007964	gestational serum measurement
EFO:0007961	polybrominated biphenyl measurement
EFO:0007962	polybrominated diphenyl ether measurement
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4523986 (PROTEIN FAMILY), CHEMBL4729 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

28 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 969,593 (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
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL135	ESTRADIOL	4	123,080
CHEMBL163	RITONAVIR	4	53,773
CHEMBL1771	CLOPIDOGREL	4	40,370
CHEMBL1873475	IBRUTINIB	4	7,994
CHEMBL190461	CANNABIDIOL	4	26,379
CHEMBL374478	RIFAMPIN	4	93,834
CHEMBL3989843	TRANYLCYPROMINE	4	70
CHEMBL4297517	MAVACAMTEN	4	208
CHEMBL638	VORICONAZOLE	4	23,088
CHEMBL651	METHADONE	4	45,280
CHEMBL671	THIOTEPA	4	117,334
CHEMBL691	ETHINYL ESTRADIOL	4	40,543
CHEMBL809	SERTRALINE	4	51,342
CHEMBL83	TAMOXIFEN	4	171,635
CHEMBL833	TICLOPIDINE	4	30,572
CHEMBL140	CURCUMIN	3	93,882
CHEMBL269671	ARTEMISININ	3	15,668
CHEMBL74415	CANNABINOL	3	18,794
CHEMBL1933349	MK-0893	2	207
CHEMBL2387742	CANNABIDIVARIN	2
CHEMBL275528	PHENCYCLIDINE	2
CHEMBL3301620	TEMSAVIR	2
CHEMBL3647536	DARIGABAT	2
CHEMBL4217292	APINOCALTAMIDE	2
CHEMBL4514636	FISOGATINIB	2
CHEMBL4649457	UDIFITIMOD	2
CHEMBL5173264	INE-963	2

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

PharmGKB clinical annotations

68 annotations.

Variant	Type	Level	Drugs	Phenotypes
CYP2B61, CYP2B62, CYP2B66, CYP2B618, CYP2B6*38	Toxicity	1A	efavirenz	HIV infectious disease
CYP2B61, CYP2B64	Toxicity	3	nicotine	Tobacco Use Disorder
CYP2B61, CYP2B64, CYP2B65, CYP2B66, CYP2B618, CYP2B622, CYP2B6*30	Metabolism/PK	2A	bupropion
CYP2B61, CYP2B64, CYP2B65, CYP2B66, CYP2B6*7	Other	3	mirtazapine	Depression
CYP2B61, CYP2B64, CYP2B65, CYP2B66, CYP2B6*7	Efficacy	3	mirtazapine	Depression
CYP2B61, CYP2B64, CYP2B66, CYP2B618	Metabolism/PK	2A	methadone	Heroin Dependence;Opioid-Related Disorders
CYP2B61, CYP2B64, CYP2B66, CYP2B69	Metabolism/PK	1A	sertraline
CYP2B61, CYP2B64, CYP2B66, CYP2B69, CYP2B618, CYP2B628	Metabolism/PK	1A	efavirenz	HIV infectious disease
CYP2B61, CYP2B65	Efficacy	3	clopidogrel
CYP2B61, CYP2B66	Efficacy,Toxicity	3	cyclophosphamide	Leukemia;Lymphocytic;Chronic;B-Cell
CYP2B61, CYP2B66	Dosage	4	methadone	Opioid-Related Disorders
CYP2B61, CYP2B66	Metabolism/PK	3	ketamine	Neoplasms;Pain
CYP2B61, CYP2B66	Metabolism/PK	3	cyclophosphamide	Lymphoma;B-Cell
CYP2B61, CYP2B66	Toxicity	3	ethambutol;isoniazid;pyrazinamide;rifampin	Tuberculosis
CYP2B61, CYP2B66	Efficacy	3	bupropion	Tobacco Use Disorder
CYP2B61, CYP2B66	Metabolism/PK	3	cotinine;nicotine	Tobacco Use Disorder
CYP2B61, CYP2B66	Metabolism/PK	3	artemether
CYP2B61, CYP2B66	Toxicity	3	methadone
CYP2B61, CYP2B66	Efficacy	3	methadone
CYP2B61, CYP2B66, CYP2B6*26	Dosage	1A	efavirenz	HIV infectious disease
CYP2B627, CYP2B628	Other	3	efavirenz
rs12721646	Other	3	nevirapine	HIV infectious disease
rs12721655	Efficacy	3	cyclophosphamide;doxorubicin	Breast Neoplasms
rs16974799	Dosage	3	methadone	Heroin Dependence
rs2054675	Toxicity	3	nevirapine	HIV infectious disease
rs2279343	Toxicity	3	cyclophosphamide	Transplantation
rs2279343	Efficacy	3	bupropion	Tobacco Use Disorder
rs2279343	Metabolism/PK	3	nicotine	Tobacco Use Disorder
rs2279343	Toxicity	3	methadone	Neonatal Abstinence Syndrome
rs2279343	Dosage	3	methadone	Heroin Dependence
rs2279343	Metabolism/PK	4	propofol
rs2279345	Metabolism/PK	3	efavirenz	HIV infectious disease;Tuberculosis
rs28399499	Toxicity	2A	nevirapine	Stevens-Johnson Syndrome;Toxic Epidermal Necrolysis
rs28399499	Metabolism/PK	3	nevirapine	HIV infectious disease
rs3211371	Toxicity	3	cyclophosphamide;doxorubicin	Breast Neoplasms
rs3211371	Efficacy	3	bupropion	Tobacco Use Disorder
rs3211371	Metabolism/PK	3	methadone
rs3211371	Metabolism/PK	4	efavirenz
rs35303484	Metabolism/PK	3	efavirenz	HIV infectious disease
rs36118214	Metabolism/PK	3	efavirenz	HIV infectious disease

PharmGKB variants

77 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs707265	CYP2B6		0.00	0
rs1042389	CYP2B6		0.00	0
rs2054675	CYP2B6	3	2.50	1	nevirapine
rs2279342	CYP2B6		0.00	0
rs2279343	CYP2B6	3	3.00	25	cyclophosphamide;methadone;nicotine;propofol;bupropion
rs2279344	CYP2B6		0.00	0
rs2279345	CYP2B6	3	7.75	1	efavirenz
rs3211371	CYP2B6	3	4.00	8	cyclophosphamide;doxorubicin;methadone;bupropion;efavirenz
rs3745274	CYP2A7P1, CYP2B6	1A	229.06	36	efavirenz;cyclophosphamide;cyclophosphamide;doxorubicin;methadone;mitotane;opioids;nevirapine;imatinib;3;4-methylenedioxymethamphetamine
rs3786547	CYP2B6	3	2.50	1	nevirapine
rs3826711	CYP2B6		0.00	1
rs4802101	CYP2B6	3	5.50	1	cyclophosphamide
rs4803419	CYP2B6	3	1.38	1	efavirenz
rs7254579	CYP2B6	3	2.00	1	cyclophosphamide
rs8192709	CYP2B6	3	2.50	4	methadone;cyclophosphamide;efavirenz
rs8192719	CYP2B6	3	1.75	1	efavirenz
rs12721646	CYP2A7P1, CYP2B6	3	0.00	1	nevirapine
rs12721655	CYP2B6	3	1.00	1	cyclophosphamide;doxorubicin
rs28399499	CYP2B6	2A	9.50	6	nevirapine
rs33926104	CYP2B6		0.00	0
rs33973337	CYP2B6		0.00	0
rs33980385	CYP2B6		0.00	0
rs34097093	CYP2B6		0.00	2
rs34223104	CYP2B6		0.00	1
rs34284776	CYP2B6		0.00	0
rs34698757	CYP2B6		0.00	2
rs34826503	CYP2B6		0.00	0
rs34883432	CYP2B6		0.00	0
rs35010098	CYP2B6		0.00	0
rs35303484	CYP2B6	3	1.75	1	efavirenz
rs35773040	CYP2B6		0.00	0
rs35979566	CYP2B6		0.00	0
rs36060847	CYP2B6		0.00	0
rs36079186	CYP2B6		0.00	1
rs36118214	CYP2B6	3	1.50	1	efavirenz
rs45482602	CYP2B6		0.00	0
rs58425034	CYP2B6	3	1.00	1	nevirapine
rs281864907	CYP2B6		0.00	1
rs8100458	CYP2B6		0.00	0
rs70950385	CYP2B6		0.00	0

PharmGKB dosing guidelines

4 guidelines.

Source	Drug	Guideline	Dosing?	Recommendation?
CPIC	efavirenz	Annotation of CPIC Guideline for efavirenz and CYP2B6	yes	yes
CPIC	methadone	Annotation of CPIC Guideline for methadone and CYP2B6
CPIC	sertraline	Annotation of CPIC Guideline for sertraline and CYP2B6, CYP2C19	yes	yes
DPWG	efavirenz	Annotation of DPWG Guideline for efavirenz and CYP2B6	yes	yes

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — CYP2 family: drug metabolising subset

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

Ligand	Action	Affinity	Parameter
ticlopidine	Inhibition	6.7	pIC50
sibutramine	Inhibition	5.79	pIC50
thiotepa	Inhibition	5.32	pKi

Binding affinities (BindingDB)

11 measured of 19 human assays (20 total across all organisms); most potent 11 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(S)-(4-fluorophenyl)-[4-[(5-methylpyrazolidin-3-yl)amino]quinazolin-2-yl]methanol	IC50	1.55 nM	US-9295672: Optically active pyrazolylaminoquinazoline, and pharmaceutical compositions and methods of use thereof
(R)-(4-fluorophenyl)-[4-[(5-methylpyrazolidin-3-yl)amino]quinazolin-2-yl]methanol	IC50	28 nM	US-9295672: Optically active pyrazolylaminoquinazoline, and pharmaceutical compositions and methods of use thereof
(5-pyridin-3-ylthiophen-2-yl)methanamine	IC50	160 nM	US-8906943: Synthetic compounds and methods to decrease nicotine self-administration
1-(4-Chlorobenzyl)-1H-imidazole	IC50	160 nM	US-8906943: Synthetic compounds and methods to decrease nicotine self-administration
3-(3-methylthiophen-2-yl)pyridine	IC50	200 nM	US-8906943: Synthetic compounds and methods to decrease nicotine self-administration
(4-fluorophenyl)-[4-[(5-methylpyrazolidin-3-yl)amino]quinazolin-2-yl]methanol	KD	1800 nM	US-9295672: Optically active pyrazolylaminoquinazoline, and pharmaceutical compositions and methods of use thereof
Tranylcypromine,(+)	KI	5960 nM
1-(3-chlorophenyl)-2-[(1-hydroxy-2-methylpropan-2-yl)amino]propan-1-one	IC50	19200 nM	US-9333197: Apoptosis signal-regulating kinase inhibitor
N-[(3S)-1-acetylpyrrolidin-3-yl]-4-[3-(3,4-difluorophenoxy)azetidin-1-yl]-1,2,5-thiadiazole-3-carboxamide	IC50	46400 nM	US-12378192: Crystalline form of capsid protein assembly inhibitor containing N hetero five-membered ring, and application thereof
1-Cyclohexylmethyl-1H-imidazole	IC50	170000 nM	US-8906943: Synthetic compounds and methods to decrease nicotine self-administration
1-(2-phenylethyl)imidazole	IC50	618000 nM	US-8906943: Synthetic compounds and methods to decrease nicotine self-administration

ChEMBL bioactivities

154 potent at pChembl≥5 of 307 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.22	IC50	60	nM	CHEMBL4175869
7.21	IC50	62	nM	CHEMBL4160749
7.14	IC50	73	nM	CHEMBL4168669
7.06	IC50	87	nM	CHEMBL4165249
7.03	IC50	93	nM	CHEMBL4161819
6.92	IC50	120	nM	CHEMBL4161400
6.75	IC50	180	nM	CHEMBL4159065
6.70	IC50	200	nM	CLOPIDOGREL
6.70	Ki	200	nM	TICLOPIDINE
6.68	IC50	210	nM	TICLOPIDINE
6.64	IC50	230	nM	CHEMBL4169324
6.60	IC50	251.2	nM	CHEMBL601428
6.47	Ki	340	nM	VORICONAZOLE
6.43	IC50	370	nM	CHEMBL4169721
6.40	Ki	400	nM	VORICONAZOLE
6.30	Ki	500	nM	CLOPIDOGREL
6.22	EC50	600	nM	ARTEMISININ
6.22	IC50	600	nM	TICLOPIDINE
6.22	Ki	600	nM	CHEMBL215134
6.16	Ki	690	nM	CANNABIDIOL
6.16	IC50	700	nM	CHEMBL3330409
6.11	IC50	780	nM	CHEMBL5273615
6.10	IC50	790	nM	VORICONAZOLE
6.10	Ki	800	nM	ETHINYL ESTRADIOL
6.10	Ki	800	nM	TICLOPIDINE
6.07	IC50	850	nM	CHEMBL4176100
6.05	Ki	900	nM	CHEMBL386124
6.05	IC50	900	nM	CHEMBL3330410
6.05	Ki	900	nM	ETHINYL ESTRADIOL
6.05	Ki	900	nM	TAMOXIFEN
5.96	IC50	1100	nM	CHEMBL2018923
5.96	Ki	1100	nM	CHEMBL214784
5.96	IC50	1100	nM	CHEMBL2130955
5.96	Ki	1100	nM	CLOPIDOGREL
5.92	IC50	1200	nM	CHEMBL4164142
5.92	IC50	1190	nM	VORICONAZOLE
5.92	Ki	1200	nM	CHEMBL1743344
5.89	EC50	1300	nM	RIFAMPIN
5.89	IC50	1300	nM	CHEMBL4173133
5.89	Ki	1300	nM	CANNABIDIVARIN
5.77	IC50	1700	nM	CHEMBL386124
5.77	IC50	1710	nM	VORICONAZOLE
5.75	IC50	1800	nM	CHEMBL5432974
5.72	Ki	1900	nM	CHEMBL179669
5.72	EC50	1900	nM	CHEMBL4850236
5.72	IC50	1900	nM	CHEMBL2130955
5.72	IC50	1900	nM	VORICONAZOLE
5.70	IC50	2000	nM	CHEMBL2018925
5.70	IC50	2000	nM	RITONAVIR
5.66	IC50	2200	nM	CHEMBL214784

PubChem BioAssay actives

141 with measured affinity, of 1763 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
8-imidazol-1-yl-5,6,7,8-tetrahydroquinoline	2022035: Inhibition of CYP450 (unknown origin)	ic50	0.0335	uM
[5-(4-phenyl-3-pyridinyl)thiophen-2-yl]methanamine;dihydrochloride	1356005: Inhibition of CYP2B6 in human liver microsomes using bupropion as substrate preincubated for 5 mins followed by addition of NADPH-regenerating system and measured after 15 mins by UPLC-MS analysis	ic50	0.0600	uM
[5-[4-(furan-3-yl)-3-pyridinyl]thiophen-2-yl]methanamine;dihydrochloride	1356005: Inhibition of CYP2B6 in human liver microsomes using bupropion as substrate preincubated for 5 mins followed by addition of NADPH-regenerating system and measured after 15 mins by UPLC-MS analysis	ic50	0.0620	uM
[5-[4-(furan-2-yl)-3-pyridinyl]thiophen-2-yl]methanamine;dihydrochloride	1356005: Inhibition of CYP2B6 in human liver microsomes using bupropion as substrate preincubated for 5 mins followed by addition of NADPH-regenerating system and measured after 15 mins by UPLC-MS analysis	ic50	0.0730	uM
[5-(4-propyl-3-pyridinyl)thiophen-2-yl]methanamine;dihydrochloride	1356005: Inhibition of CYP2B6 in human liver microsomes using bupropion as substrate preincubated for 5 mins followed by addition of NADPH-regenerating system and measured after 15 mins by UPLC-MS analysis	ic50	0.0870	uM
[5-(4-ethyl-3-pyridinyl)thiophen-2-yl]methanamine;dihydrochloride	1356005: Inhibition of CYP2B6 in human liver microsomes using bupropion as substrate preincubated for 5 mins followed by addition of NADPH-regenerating system and measured after 15 mins by UPLC-MS analysis	ic50	0.0930	uM
5-(2,4,5-trichlorophenoxy)pyridin-2-amine	1416594: Inhibition of CYP2B6 (unknown origin)	ic50	0.1000	uM
[5-[4-(furan-2-yl)-3-pyridinyl]furan-2-yl]methanamine;dihydrochloride	1356005: Inhibition of CYP2B6 in human liver microsomes using bupropion as substrate preincubated for 5 mins followed by addition of NADPH-regenerating system and measured after 15 mins by UPLC-MS analysis	ic50	0.1200	uM
[5-(4-phenyl-3-pyridinyl)furan-2-yl]methanamine;dihydrochloride	1356005: Inhibition of CYP2B6 in human liver microsomes using bupropion as substrate preincubated for 5 mins followed by addition of NADPH-regenerating system and measured after 15 mins by UPLC-MS analysis	ic50	0.1800	uM
Ticlopidine	589240: Mechanism based inhibition of human cytochrome P450 2B6 measured by bupropion hydroxylation using human liver microsomes	ki	0.2000	uM
[5-[4-(furan-3-yl)-3-pyridinyl]furan-2-yl]methanamine;dihydrochloride	1356005: Inhibition of CYP2B6 in human liver microsomes using bupropion as substrate preincubated for 5 mins followed by addition of NADPH-regenerating system and measured after 15 mins by UPLC-MS analysis	ic50	0.2300	uM
N-(4-chlorophenyl)-5-ethyl-N-methyl-3-phenyl-1,2-oxazole-4-carboxamide	2108148: Inhibition of CYP450 (unknown origin)	ic50	0.2512	uM
Voriconazole	541850: Inhibition of CYP2B6 in human liver microsomes assessed as bupropion 4-hydroxylation after 15 mins by Dixon plot analysis	ki	0.3400	uM
[5-(4-propyl-3-pyridinyl)furan-2-yl]methanamine;dihydrochloride	1356005: Inhibition of CYP2B6 in human liver microsomes using bupropion as substrate preincubated for 5 mins followed by addition of NADPH-regenerating system and measured after 15 mins by UPLC-MS analysis	ic50	0.3700	uM
Clopidogrel	589244: Mechanism based inhibition of human cytochrome P450 2B6 using human liver microsomes	ki	0.5000	uM
(5-phenylthiophen-2-yl)methanamine	272643: Inhibition of human CYP2B6	ki	0.6000	uM
(1R,4S,5R,8S,9R,12S,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-one	1212120: Induction of CYP2B6 in human hepatocytes after 72 hrs relative to vehicle-treated control	ec50	0.6000	uM
Cannabidiol	1692719: Mixed type inhibition of human recombinant CYP2B6 expressed in baculovirus-infected insect cells using coumarin as substrate preincubated for 5 mins followed by NADPH-generating system addition by Lineweaver-Burk plot analysis	ki	0.6900	uM
2-(dimethylamino)-2-(2-ethylphenyl)-N-[3-(3-sulfamoylphenyl)-1H-indazol-5-yl]acetamide	2119433: Inhibition of CYP450 (unknown origin)	ic50	0.7000	uM
1-(4-methylphenyl)-3-[7-[2-(3-oxo-1,2,4-oxadiazol-5-yl)phenyl]-5-phenyl-2,3,4,5-tetrahydro-1-benzoxepin-9-yl]urea	1955446: Inhibition of CYP2B6 (unknown origin)	ic50	0.7800	uM
ethinyl estradiol	589235: Mechanism based inhibition of human cytochrome P450 2B6 measured by 7-EFC O-deethylation	ki	0.8000	uM
[5-(4-methyl-3-pyridinyl)thiophen-2-yl]methanamine;dihydrochloride	1356005: Inhibition of CYP2B6 in human liver microsomes using bupropion as substrate preincubated for 5 mins followed by addition of NADPH-regenerating system and measured after 15 mins by UPLC-MS analysis	ic50	0.8500	uM
2-pyrrolidin-1-yl-N-[3-(3-sulfamoylphenyl)-1H-indazol-5-yl]-2-thiophen-3-ylacetamide	2119433: Inhibition of CYP450 (unknown origin)	ic50	0.9000	uM
S-[(5-pyridin-3-ylfuran-2-yl)methyl] ethanethioate	272643: Inhibition of human CYP2B6	ki	0.9000	uM
Tamoxifen	589238: Mechanism based inhibition of human cytochrome P450 2B6 measured by 7-EFC O-deethylation	ki	0.9000	uM
(5-pyridin-3-ylfuran-2-yl)methanethiol	272643: Inhibition of human CYP2B6	ki	1.1000	uM
2-[4-(trifluoromethyl)phenyl]chromen-4-one	1860369: Inhibition of CYP450 in human HCT-116 cells assessed as 20-HETE formation in presence of arachidonic acid incubated for 15 mins by multi-enzyme assay based LC-MS/MS analysis	ic50	1.1000	uM
6-methoxy-2-[(3-phenylphenyl)methylsulfanyl]-1H-benzimidazole	656027: Inhibition of CYP2B6 in human liver microsomes using bupropion as substrate preincubated for 5 mins by LC-MS/MS analysis	ic50	1.1000	uM
[5-(4-pyridin-3-yl-3-pyridinyl)thiophen-2-yl]methanamine;trihydrochloride	1356005: Inhibition of CYP2B6 in human liver microsomes using bupropion as substrate preincubated for 5 mins followed by addition of NADPH-regenerating system and measured after 15 mins by UPLC-MS analysis	ic50	1.2000	uM
1-(2-phenylpropan-2-yl)piperidine	589232: Mechanism based inhibition of human cytochrome P450 2B6	ki	1.2000	uM
2-[(1R,6R)-3-methyl-6-prop-1-en-2-ylcyclohex-2-en-1-yl]-5-propylbenzene-1,3-diol	1845643: Mixed inhibition of recombinant CYP2B6 (unknown origin) using coumarin as substrate in presence of NADPH-generating system by Lineweaver-burk plots analysis	ki	1.3000	uM
rifampin	1210066: Induction of CYP2B6 activity in human donor hepatocytes assessed as hydroxybupropion formation after 48 hrs by LC/MS method	ec50	1.3000	uM
[5-(4-ethyl-3-pyridinyl)furan-2-yl]methanamine;dihydrochloride	1356005: Inhibition of CYP2B6 in human liver microsomes using bupropion as substrate preincubated for 5 mins followed by addition of NADPH-regenerating system and measured after 15 mins by UPLC-MS analysis	ic50	1.3000	uM
2-imidazol-1-yl-N-(4-methoxycyclohexyl)pyrimidine-4-carboxamide	2014497: Inhibition of CYP2B6 in human liver microsomes preincubated for 5 mins in presence of substrate followed by NADPH addition and measured after 10 mins by LC/MS analysis	ic50	1.8000	uM
(3aR,6aS)-2-(oxan-4-ylmethyl)-N-[6-(2,3,5-trifluorophenyl)pyridazin-3-yl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-5-amine	1779762: Induction of CYP2B6 in human hepatocytes	ec50	1.9000	uM
3-(3-methylthiophen-2-yl)pyridine	272643: Inhibition of human CYP2B6	ki	1.9000	uM
Ritonavir	520314: Inhibition of human CYP2B6 in human liver microsomes	ic50	2.0000	uM
6-methoxy-2-[(3-phenoxyphenyl)methylsulfanyl]-1H-benzimidazole	656027: Inhibition of CYP2B6 in human liver microsomes using bupropion as substrate preincubated for 5 mins by LC-MS/MS analysis	ic50	2.0000	uM
Thiotepa	589243: Mechanism based inhibition of human cytochrome P450 2B6 measured by bupropion hydroxylation using a recombinant system	ki	2.2000	uM
4-N-[(1S)-1,2,3,4-tetrahydronaphthalen-1-yl]-4-N-[[(7R)-5,6,7,8-tetrahydro-1,6-naphthyridin-7-yl]methyl]cyclohexane-1,4-diamine	2124397: Inhibition of CYP450 (unknown origin)	ic50	2.5000	uM
6,6,9-trimethyl-3-pentylbenzo[c]chromen-1-ol	1845659: Inhibition of recombinant human CYP2B6 using coumarin as substrate preincubated with NADPH for 20 mins and measured after 30 min by Lineweaver-burk plots analysis	ki	2.5500	uM
3-(4-phenyl-3-pyridinyl)prop-2-yn-1-amine;dihydrochloride	1356005: Inhibition of CYP2B6 in human liver microsomes using bupropion as substrate preincubated for 5 mins followed by addition of NADPH-regenerating system and measured after 15 mins by UPLC-MS analysis	ic50	3.0000	uM
3-(4-methylthiophen-3-yl)pyridine	272643: Inhibition of human CYP2B6	ki	3.1000	uM
N-[(1R,3S)-3-[(8aS)-6-oxo-1,3,4,7,8,8a-hexahydropyrrolo[1,2-a]pyrazin-2-yl]cyclohexyl]-4-fluoro-7-methyl-1H-indole-2-carboxamide	1870244: Inhibition of CYP2B6 in human liver microsomes using bupropion as substrate preincubated for 5 mins followed by NADPH addition measured after 20 mins by LC-MS/MS analysis	ic50	3.2000	uM
[5-(4-pyridin-4-yl-3-pyridinyl)thiophen-2-yl]methanamine;trihydrochloride	1356005: Inhibition of CYP2B6 in human liver microsomes using bupropion as substrate preincubated for 5 mins followed by addition of NADPH-regenerating system and measured after 15 mins by UPLC-MS analysis	ic50	3.5000	uM
3-[4-(furan-3-yl)-3-pyridinyl]prop-2-yn-1-amine;dihydrochloride	1356005: Inhibition of CYP2B6 in human liver microsomes using bupropion as substrate preincubated for 5 mins followed by addition of NADPH-regenerating system and measured after 15 mins by UPLC-MS analysis	ic50	3.5000	uM
2-[(4-chlorophenyl)methylsulfanyl]-6-methoxy-1H-benzimidazole	656027: Inhibition of CYP2B6 in human liver microsomes using bupropion as substrate preincubated for 5 mins by LC-MS/MS analysis	ic50	3.6000	uM
1-[3-(2,4-dimethoxyphenyl)phenyl]-2,4-dimethoxybenzene	1973305: Inhibition of CYP450 in pooled human liver microsomes in presence of NADPH measured every 3 mins for 120 mins by fluorescence based analysis	ic50	3.7000	uM
1-[(E)-2-(2,4-dimethoxyphenyl)ethenyl]-3,5-dimethoxybenzene	1973305: Inhibition of CYP450 in pooled human liver microsomes in presence of NADPH measured every 3 mins for 120 mins by fluorescence based analysis	ic50	3.7000	uM
(5-phenylfuran-2-yl)methanamine	272643: Inhibition of human CYP2B6	ki	3.8000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Phenobarbital	increases expression, affects cotreatment, affects reaction, increases reaction, increases activity (+2 more)	52
Rifampin	affects reaction, increases reaction, increases activity, affects cotreatment, decreases reaction (+1 more)	39
6-(4-chlorophenyl)imidazo(2,1-b)(1,3)thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime	affects cotreatment, decreases reaction, increases reaction, affects binding, increases activity (+1 more)	29
Bupropion	increases hydroxylation, decreases activity, increases hydrolysis, affects metabolic processing, increases chemical synthesis (+3 more)	23
Cyclophosphamide	increases hydroxylation, increases response to substance, affects cotreatment, increases reaction, decreases expression (+8 more)	15
Chlorpyrifos	affects cotreatment, decreases reaction, increases chemical synthesis, affects metabolic processing, increases expression (+4 more)	14
Methoxychlor	increases chemical synthesis, increases activity, decreases methylation, increases hydroxylation, increases metabolic processing (+5 more)	12
Phenytoin	affects reaction, increases expression, increases reaction, decreases reaction, increases activity	11
perfluorooctane sulfonic acid	affects cotreatment, increases expression, decreases reaction, increases oxidation, decreases expression	8
Benzo(a)pyrene	decreases expression, affects methylation, decreases reaction, increases methylation, increases mutagenesis (+3 more)	8
Endosulfan	decreases activity, increases activity, increases reaction, decreases reaction, affects cotreatment (+2 more)	8
perfluorooctanoic acid	affects cotreatment, increases expression	7
hydroxybupropion	increases chemical synthesis, increases hydroxylation, increases metabolic processing, decreases reaction	6
Troglitazone	increases expression, increases activity, affects cotreatment	6
efavirenz	increases expression, affects metabolic processing, increases metabolic processing, decreases activity, decreases metabolic processing (+1 more)	5
Dexamethasone	increases expression, increases reaction, increases activity, affects cotreatment, affects reaction	5
Ticlopidine	decreases activity, affects metabolic processing, decreases reaction, increases metabolic processing, affects binding	5
artemisinin	affects metabolic processing, increases activity, increases expression	4
metolachlor	affects cotreatment, decreases response to substance, increases degradation, increases metabolic processing	4
7-ethoxy-4-trifluoromethylcoumarin	decreases ethylation, increases metabolic processing, increases chemical synthesis, increases oxidation, decreases reaction	4
cyproconazole	affects cotreatment, increases expression	4
2,2’,4,4’-tetrabromodiphenyl ether	affects expression, increases activity, increases expression, increases chemical synthesis, increases metabolic processing	4
Carbamazepine	increases activity, increases expression, increases response to substance	4
DEET	decreases reaction, increases metabolic processing, increases expression, affects cotreatment	4
Mephenytoin	decreases methylation, increases metabolic processing, decreases ethylation, decreases reaction, increases chemical synthesis (+2 more)	4
NADP	affects cotreatment, increases metabolic processing, decreases activity, decreases reaction	4
Thiotepa	affects export, affects response to substance, decreases reaction, increases hydrolysis, increases hydroxylation (+1 more)	4
Tobacco Smoke Pollution	decreases expression, increases expression	4
Valproic Acid	increases metabolic processing, increases response to substance, decreases methylation, increases expression	4
Particulate Matter	increases abundance, increases expression, affects response to substance, decreases expression	4

ChEMBL screening assays

861 unique, capped per target: 851 admet, 10 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2060324	ADMET	Inhibition of CYP450	Rapid identification of ETP-46992, orally bioavailable PI3K inhibitor, selective versus mTOR. — Bioorg Med Chem Lett
CHEMBL4614611	Binding	Drug metabolism in human liver microsomes assessed as Cytochrome P450-mediated formation of 12-OHNVP by measuring Kcat/Km ratio in presence of NADPH regenerating reagents by uHPLC-MS/MS analysis	Twelfth-Position Deuteration of Nevirapine Reduces 12-Hydroxy-Nevirapine Formation and Nevirapine-Induced Hepatocyte Death. — J Med Chem

Cellosaurus cell lines

9 cell lines: 5 cancer cell line, 2 spontaneously immortalized cell line, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B5VY	Hepc/2B6.68	Cancer cell line	Male
CVCL_C0V4	HepG2 CAR-CYP2B6 clone 6	Cancer cell line	Male
CVCL_C0V5	HepG2 CAR-CYP2B6 clone 7	Cancer cell line	Male
CVCL_C0V6	HepG2 CAR-CYP2B6 clone 10	Cancer cell line	Male
CVCL_D1GP	CHO-CPR/CYP2B6 C8	Spontaneously immortalized cell line	Female
CVCL_D1GS	CHO-CYP2B6 C1	Spontaneously immortalized cell line	Female
CVCL_IQ15	THLE-5B-2B6	Transformed cell line	Sex unspecified
CVCL_UG89	HEK293 CYP2B6*1-V5	Transformed cell line	Female
CVCL_XI69	HepG2-CYP2B6-hCAR	Cancer cell line	Male

Clinical trials (associated diseases)

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