CYP2D6

Summary

CYP2D6 (cytochrome P450 family 2 subfamily D member 6 (gene/pseudogene), HGNC:2625) is a protein-coding gene on chromosome 22q13.2, encoding Cytochrome P450 2D6 (P10635). A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids.

This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and is known to metabolize as many as 25% of commonly prescribed drugs. Its substrates include antidepressants, antipsychotics, analgesics and antitussives, beta adrenergic blocking agents, antiarrythmics and antiemetics. The gene is highly polymorphic in the human population; certain alleles result in the poor metabolizer phenotype, characterized by a decreased ability to metabolize the enzyme’s substrates. Some individuals with the poor metabolizer phenotype have no functional protein since they carry 2 null alleles whereas in other individuals the gene is absent. This gene can vary in copy number and individuals with the ultrarapid metabolizer phenotype can have 3 or more active copies of the gene. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 1565 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 353 total — 1 pathogenic
• Phenotypes (HPO): 3
• Druggable target: yes — 436 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000106

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2625
Approved symbol	CYP2D6
Name	cytochrome P450 family 2 subfamily D member 6 (gene/pseudogene)
Location	22q13.2
Locus type	gene with protein product
Status	Approved
Aliases	CPD6, P450-DB1, CYP2D, P450C2D
Ensembl gene	ENSG00000100197
Ensembl biotype	protein_coding
OMIM	124030
Entrez	1565

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 32 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000359033, ENST00000360124, ENST00000488442, ENST00000645361, ENST00000852651, ENST00000852652, ENST00000852653, ENST00000852654, ENST00000852655, ENST00000852656, ENST00000852657, ENST00000852658, ENST00000852659, ENST00000852660, ENST00000852661, ENST00000852662, ENST00000852663, ENST00000852664, ENST00000852665, ENST00000852666, ENST00000852667, ENST00000852668, ENST00000852669, ENST00000852670, ENST00000852671, ENST00000852672, ENST00000852673, ENST00000852674, ENST00000852675, ENST00000852676, ENST00000852677, ENST00000852678, ENST00000852679, ENST00000963586

RefSeq mRNA: 2 — MANE Select: NM_000106 NM_000106, NM_001025161

CCDS: CCDS33657, CCDS46721

Canonical transcript exons

ENST00000607853 — 0 exons

Expression profiles

Bgee: expression breadth ubiquitous, 131 present calls, max score 99.03.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0385 / max 23.0015, expressed in 10 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
194411	0.0385	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	99.03	gold quality
liver	UBERON:0002107	98.17	gold quality
duodenum	UBERON:0002114	90.43	gold quality
small intestine Peyer’s patch	UBERON:0003454	81.81	gold quality
sural nerve	UBERON:0015488	81.68	gold quality
small intestine	UBERON:0002108	81.50	gold quality
right hemisphere of cerebellum	UBERON:0014890	79.62	gold quality
right uterine tube	UBERON:0001302	79.11	gold quality
cerebellar hemisphere	UBERON:0002245	78.04	gold quality
cerebellum	UBERON:0002037	77.98	gold quality
cerebellar cortex	UBERON:0002129	77.98	gold quality
pituitary gland	UBERON:0000007	77.61	gold quality
right lobe of thyroid gland	UBERON:0001119	77.50	gold quality
left lobe of thyroid gland	UBERON:0001120	77.46	gold quality
thyroid gland	UBERON:0002046	76.78	gold quality
nucleus accumbens	UBERON:0001882	75.52	gold quality
adenohypophysis	UBERON:0002196	75.43	gold quality
left ovary	UBERON:0002119	75.26	gold quality
left testis	UBERON:0004533	75.23	gold quality
right testis	UBERON:0004534	75.07	gold quality
mucosa of transverse colon	UBERON:0004991	74.95	gold quality
putamen	UBERON:0001874	74.66	gold quality
metanephros cortex	UBERON:0010533	74.00	gold quality
testis	UBERON:0000473	73.96	gold quality
ovary	UBERON:0000992	73.68	gold quality
lower esophagus mucosa	UBERON:0035834	73.59	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	73.36	gold quality
cortex of kidney	UBERON:0001225	73.32	gold quality
right ovary	UBERON:0002118	73.28	gold quality
caudate nucleus	UBERON:0001873	73.26	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BHLHE41, CEBPA, HNF4A, HNF4G, NR0B2, NR2F1

Literature-anchored findings (GeneRIF, showing 40)

• Anti-CYP2D6 antibodies detected by quantitative radioligand assay and relation to antibodies to liver-specific arginase in patients with autoimmune hepatitis. (PMID:11750286)
• CYP2D6 catalyzes the major metabolic pathway of fluvoxamine. (PMID:11791895)
• determination of phenotype in liver microsomes (PMID:11816009)
• polymorphisms and atypical antipsychotic weight gain (PMID:11901361)
• CYP2D6 genotype is associated with antipsychotic-induced extrapyramidal syndromes (PMID:11927839)
• treatment-resistant schizophrenia -duplication in the cytochrome P450IID6 (CYP2D6) gene (PMID:11940091)
• The antigenic constitution of CYP2D6, the major target of liver kidney microsomal antibody type 1 in type 2 autoimmune hepatitis and chronic hepatitis C virus infections, has been initially characterized. (PMID:12077255)
• demonstrate constitutive expression of cytochrome P4502D in neuronal cell population in human brain, indicating its possible role in metabolism of psychoactive drugs directly at or near their site of action, in neurons, in human brain. (PMID:12106691)
• results indicate a significant influence of environmental factors as an explanation for the difference in capacity for CYP2D6, but not CYP2C19 metabolism between Caucasians and Black Africans (PMID:12142727)
• lower activity observed in a black American population is in part attributable to the presence of variant alleles that occur at a higher frequency in this population than in white subjects (PMID:12152006)
• Patients who had homozygous (L/L) or heterozygous (Wt/L) mutant alleles developed manganism an average of 10 years later than those who were homozygous wildtype (PMID:12171760)
• the pronounced effect of the CYP2D6 genotype persists during long-term therapy, affecting both metabolic ratio and metoprolol plasma concentration. (PMID:12172215)
• Duplicated alleles of CYP2D6*10 exist in the Japanese population and that it may be one of the factors affecting the capacity of Japanese to metabolize various CYP2D6 substrate drugs. (PMID:12175908)
• Study of oxidation of non-amine ligands and substrates by cytochrome P450 2D6 reveals lack of an obligatory role for Asp-301 in substrate electrostatic bonding. (PMID:12206675)
• This study suggests that these polymorphisms are not related to the development of tardive dystonia. (PMID:12210290)
• contributes to the biotransformation of E- and X-doxepin in healthy volunteers (PMID:12360109)
• an alteration in position of active-site residues in CYP2D6.17 as a possible explanation for the reduced activity of the enzyme. (PMID:12392820)
• The functional differences between CYP2D6.1, CYP2D6.2, CYP2D6.10, and CYP2D6.17 allelic isoforms toward three clinically important substrates have been compared, and alterations in their metabolic capacities have been demonstrated. (PMID:12438554)
• new allelic arrangement in a poor metabolizer in debrisoquine (PMID:12439227)
• role of glutatmate 216 and aspartate 301 in determining substrate specificity and product regioselectivity (PMID:12446689)
• We have examined frequency of the CYP2D6*4 allele of debrisoquine hydroxylase (DBH) involving G/A transition at the intron 3-exon 4 junction in dementia with Lewy bodies[DLB]; this allele does not act as a risk factor for DLB (PMID:12486288)
• patients with impaired CYP2D6 enzyme activity due to enzyme inhibition by thioridazine might be more prone to increased risk of sudden death due to torsade de pointes type cardiac dysrhythmia (PMID:12503836)
• Male schizophrenics with at least one decreased or loss of function allele for CYP2D6 have a moderately greater chance of developing tardive dyskinesia than males with only wild-type alleles. (PMID:12629505)
• These results do not support the hypothesis that CYP2D6 activity affects temperament and character. (PMID:12782969)
• CYP2D6 gene is a marker for genetic susceptibility to allergic perennial rhinitis (PMID:12879776)
• CYP2C9 and CYP2C19 provided enhanced formation of R-EDDP from methadone and CYP2D6 incubation resulted in the preferential conversion to S-EDDP. (PMID:12900870)
• CYP2D6 and CYP2C19 do not significantly contribute to the metabolism of Methaqualone; although interindividual differences in the monitored metabolic patterns were noted, no marked difference could be related to a CYP2D6 or CYP2C19 polymorphism. (PMID:12900872)
• The prevalence of CYP2D6 mutations of allelic variants predict genotype frequency in the Croatian population. (PMID:12950145)
• Homozygotes of CYP2D6*2 and CYP2D6*10 appear to be a susceptibility factor for developing acute extrapyramidal symptoms in schizophrenic patients. (PMID:12960748)
• CYP2D6 genotype has an impact on analgesia with tramadol. Pharmacogenetics may explain some of the varying response to pain medication in postoperative patients. (PMID:14499440)
• Cytochrome P(450)IID6’s activity may play a role in the development of Type 1 diabetes mellitus. (PMID:14726620)
• The CYP2D6*10 C188T polymorphism may be associated with the susceptibility to the occurrence of TD induced by typical antipsychotics, especially in male patients, and may also be correlated with AIMS scores in TD patients. (PMID:15118351)
• carriers with three functional CYP2D6 genes, CYP2D6*1 x 2/*2 or CYP2D6*1/*2 x 2, are ultrarapid metabolizer phenotypes and there is no gene-dose between carriers with two and three CYP2D6*10 mutated genes (PMID:15149890)
• CYP2D6,…expressed at rather low levels compared to… other human CYPs, plays an important role in metabolism, partially or to a major extent for the oxidative biotransformation of a variety of psychoactive and cardiovascular drugs. (PMID:15177309)
• polymorphic CYP2D6 may play an important role in the interconversions of these psychoactive tryptamines, including a crucial step in a serotonin-melatonin cycle (Review) (PMID:15237854)
• “…the present results show that CYP2D6, but not CYP2C9, may be related to QTc lengthening during treatment with risperidone.” pp 191-192. (PMID:15260906)
• Results describe the effects of genetic polymorphism of cytochrome P450 2D6 on the metabolism of neuroactive steroids and amines in the brain. (PMID:15469888)
• Three new alternative splicing variants of CYP2D6 mRNA have been identified. (PMID:15484318)
• Five novel nonsynonymous single nucleotide polymorphisms are reported and 65 other sequence variations detected from the gene coding for cytochrome P450 (CYP) 2D6 in 254 Japanese subjects. (PMID:15499201)
• Poor CYP2D6 metabolizers may be at higher risk of adverse reactions to metoprolol. (PMID:15646732)

Cross-species orthologs

14 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cyp2d26	ENSMUSG00000022445
mus_musculus	Cyp2d22	ENSMUSG00000061740
mus_musculus	Cyp2d40	ENSMUSG00000068083
mus_musculus	Cyp2d11	ENSMUSG00000068085
mus_musculus	Cyp2d9	ENSMUSG00000068086
mus_musculus	Cyp2d34	ENSMUSG00000094559
mus_musculus	Cyp2d10	ENSMUSG00000094806
mus_musculus	Cyp2d12	ENSMUSG00000096852
mus_musculus	Cyp2d13	ENSMUSG00000118516
rattus_norvegicus	Cyp2d2	ENSRNOG00000008988
rattus_norvegicus	Cyp2d4	ENSRNOG00000032261
rattus_norvegicus		ENSRNOG00000077236
rattus_norvegicus	Cyp2d3	ENSRNOG00000080638
rattus_norvegicus	Cyp2d1	ENSRNOG00000084482

Paralogs (15): CYP2W1 (ENSG00000073067), CYP2C18 (ENSG00000108242), CYP2E1 (ENSG00000130649), CYP2J2 (ENSG00000134716), CYP2C9 (ENSG00000138109), CYP2C8 (ENSG00000138115), CYP2U1 (ENSG00000155016), CYP2C19 (ENSG00000165841), CYP2S1 (ENSG00000167600), CYP2R1 (ENSG00000186104), CYP2B6 (ENSG00000197408), CYP2F1 (ENSG00000197446), CYP2A13 (ENSG00000197838), CYP2A7 (ENSG00000198077), CYP2A6 (ENSG00000255974)

Protein

Protein identifiers

Cytochrome P450 2D6 — P10635 (reviewed: P10635)

Alternative names: CYPIID6, Cholesterol 25-hydroxylase, Cytochrome P450-DB1, Debrisoquine 4-hydroxylase

All UniProt accessions (3): P10635, C1ID52, H7BY38

UniProt curated annotations — full annotation on UniProt →

Function. A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH–hemoprotein reductase). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling. Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis. Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid. Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.

Subcellular location. Endoplasmic reticulum membrane. Microsome membrane.

Induction. By pregnancy.

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

Polymorphism. Genetic variations in CYP2D6 are the cause of poor drug metabolism CYP2D6-related [MIM:608902]. The CYP2D6 gene is highly polymorphic. CYP2D6 activity ranges widely within a population comprising ultrarapid (UM), extensive (EM), intermediate (IM) and poor (PM) metabolizer phenotypes. UM and PM are those most at risk for treatment failure or dose-dependent drug toxicity, respectively. Of the Caucasian populations of Europe and North America, 5%-10% are of the PM phenotype and are unable to metabolize the antihypersensitive drug debrisoquine and numerous other drugs. Different alleles are known, including CYP2D61, CYP2D62, CYP2D66B/6C, CYP2D67 also known CYP2D6E, CYP2D69 also known CYP2D6C, CYP2D610 also known CYP2D6J, CYP2D612, CYP2D614, CYP2D617 also known CYP2D6Z, CYP2D641B, CYP2D645A, CYP2D645B, CYP2D646, CYP2D687, CYP2D688, CYP2D689, CYP2D690, CYP2D691, CYP2D693, C CYP2D694, CYP2D697 and CYP2D698. Isozymes CYP2D6.45 (Lys-155, Cys-296 and Thr-486) and CYP2D6.46 (His-26, Lys-155, Cys-296 and Thr-486) are functional. The sequence shown is that of isozyme CYP2D6.1 corresponding to allele CYP2D6*1.

Similarity. Belongs to the cytochrome P450 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P10635-1	1	yes
P10635-2	2

RefSeq proteins (2): NP_000097, NP_001020332 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001128	Cyt_P450	Family
IPR002401	Cyt_P450_E_grp-I	Family
IPR008069	Cyt_P450_E_grp-I_CYP2D-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)
• EC 1.14.99.38 — cholesterol 25-monooxygenase (BRENDA: 12 organisms, 12 substrates, 2 inhibitors, 0 Km, 0 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), 12 shown:

• (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + reduced [NADPH–hemoprotein reductase] + O2 = (17S,18R)-epoxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:39783)
• all-trans-retinol + reduced [NADPH–hemoprotein reductase] + O2 = all-trans-retinal + oxidized [NADPH–hemoprotein reductase] + 2 H2O + H(+) (RHEA:42092)
• (5Z,8Z,11Z,14Z)-eicosatetraenoate + reduced [NADPH–hemoprotein reductase] + O2 = (14S,15R)-epoxy-(5Z,8Z,11Z)-eicosatrienoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:49856)
• (5Z,8Z,11Z,14Z)-eicosatetraenoate + reduced [NADPH–hemoprotein reductase] + O2 = (11R,12S)-epoxy-(5Z,8Z,14Z)-eicosatrienoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:49880)
• (5Z,8Z,11Z,14Z)-eicosatetraenoate + reduced [NADPH–hemoprotein reductase] + O2 = (8R,9S)-epoxy-(5Z,11Z,14Z)-eicosatrienoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:49884)
• cholesterol + reduced [NADPH–hemoprotein reductase] + O2 = 25-hydroxycholesterol + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:50256)
• (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + reduced [NADPH–hemoprotein reductase] + O2 = (19R,20S)-epoxy-(4Z,7Z,10Z,13Z,16Z)-docosapentaenoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:52120)
• (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + reduced [NADPH–hemoprotein reductase] + O2 = (19S,20R)-epoxy-(4Z,7Z,10Z,13Z,16Z)-docosapentaenoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:52124)
• 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)
• N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + reduced [NADPH–hemoprotein reductase] + O2 = N-(20-hydroxy-5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:53152)

UniProt features (97 total): sequence variant 50, helix 22, strand 15, turn 5, binding site 2, chain 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
3TBG	X-RAY DIFFRACTION	2.1
4WNU	X-RAY DIFFRACTION	2.26
4WNV	X-RAY DIFFRACTION	2.35
6CSD	X-RAY DIFFRACTION	2.39
6CSB	X-RAY DIFFRACTION	2.39
4XRZ	X-RAY DIFFRACTION	2.4
4XRY	X-RAY DIFFRACTION	2.5
4WNT	X-RAY DIFFRACTION	2.6
3TDA	X-RAY DIFFRACTION	2.67
5TFT	X-RAY DIFFRACTION	2.71
5TFU	X-RAY DIFFRACTION	2.75
3QM4	X-RAY DIFFRACTION	2.85
2F9Q	X-RAY DIFFRACTION	3
4WNW	X-RAY DIFFRACTION	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P10635-F1	94.55	0.84

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 (2): 301; 443 (axial binding residue)

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-211935	Fatty acids
R-HSA-211958	Miscellaneous substrates
R-HSA-211981	Xenobiotics
R-HSA-211999	CYP2E1 reactions
R-HSA-9027307	Biosynthesis of maresin-like SPMs
R-HSA-9749641	Aspirin ADME

MSigDB gene sets: 203 (showing top): CREL_01, REACTOME_BIOLOGICAL_OXIDATIONS, MORF_MSH3, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, GNF2_GSTM1, GNF2_HPN, 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, RIZKI_TUMOR_INVASIVENESS_3D_DN, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, USF_C, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS

GO Biological Process (17): xenobiotic metabolic process (GO:0006805), steroid metabolic process (GO:0008202), cholesterol metabolic process (GO:0008203), estrogen metabolic process (GO:0008210), coumarin metabolic process (GO:0009804), alkaloid metabolic process (GO:0009820), alkaloid catabolic process (GO:0009822), monoterpenoid metabolic process (GO:0016098), arachidonate metabolic process (GO:0019369), isoquinoline alkaloid metabolic process (GO:0033076), xenobiotic catabolic process (GO:0042178), retinol metabolic process (GO:0042572), long-chain fatty acid biosynthetic process (GO:0042759), oxidative demethylation (GO:0070989), negative regulation of organofluorine metabolic process (GO:0090350), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631)

GO Molecular Function (10): monooxygenase activity (GO:0004497), iron ion binding (GO:0005506), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen (GO:0016712), heme binding (GO:0020037), anandamide 8,9 epoxidase activity (GO:0062187), anandamide 11,12 epoxidase activity (GO:0062188), anandamide 14,15 epoxidase activity (GO:0062189), oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen (GO:0016705), metal ion binding (GO:0046872)

GO Cellular Component (5): cytoplasm (GO:0005737), mitochondrion (GO:0005739), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
anandamide epoxidase activity	3
metabolic process	2
lipid metabolic process	2
hormone metabolic process	2
catabolic process	2
alkaloid metabolic process	2
long-chain fatty acid metabolic process	2
olefinic compound metabolic process	2
oxidoreductase activity	2
cellular anatomical structure	2
cytoplasm	2
intracellular membrane-bounded organelle	2
cellular response to xenobiotic stimulus	1
sterol metabolic process	1
secondary alcohol metabolic process	1
steroid metabolic process	1
phenylpropanoid metabolic process	1
terpenoid metabolic process	1
icosanoid metabolic process	1
unsaturated fatty acid metabolic process	1
xenobiotic metabolic process	1
retinoid metabolic process	1
primary alcohol metabolic process	1
fatty acid biosynthetic process	1
demethylation	1
negative regulation of metabolic process	1
organofluorine metabolic process	1
regulation of organohalogen metabolic process	1
primary metabolic process	1
monocarboxylic acid metabolic process	1
transition metal ion binding	1
catalytic activity	1
monooxygenase activity	1
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	1
tetrapyrrole binding	1
cation binding	1
intracellular anatomical structure	1
endomembrane system	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1

Protein interactions and networks

STRING

2142 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CYP2D6	PPIG	Q13427	961
CYP2D6	TPMT	P51580	902
CYP2D6	SLCO1B1	Q9Y6L6	853
CYP2D6	UGT1A6	P19224	834
CYP2D6	B3GAT2	Q9NPZ5	811
CYP2D6	UGT1A4	P22310	796
CYP2D6	NAT2	P11245	783
CYP2D6	UGT2B7	P16662	777
CYP2D6	UGT1A8	Q9HAW9	777
CYP2D6	UGT1A1	P22309	776
CYP2D6	UGT1A10	Q9HAW8	776
CYP2D6	UGT1A7	Q9HAW7	776
CYP2D6	VKORC1	Q9BQB6	769
CYP2D6	ABCB1	P08183	767
CYP2D6	SLC35A2	P78381	723

IntAct

2 interactions, top by confidence:

A	B	Type	Score
CYP2D6	ATRAID	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (7): ATRAID (Affinity Capture-MS), CYP2D6 (Reconstituted Complex), CYP2D6 (Reconstituted Complex), CYP2D6 (Reconstituted Complex), POR (Reconstituted Complex), CYP2D6 (Co-crystal Structure), CYP2D6 (Co-crystal Structure)

ESM2 similar proteins: A0A087X1C5, E9Q816, O18992, O46658, P00191, P03940, P08686, P10633, P10634, P10635, P11714, P12394, P12938, P12939, P15540, P24456, P24457, P30437, P51589, P51590, P52786, P70085, P78329, Q01361, Q0IIF9, Q29473, Q29488, Q2LA59, Q2LA60, Q2LCM1, Q2XNC8, Q2XNC9, Q4V8D1, Q64403, Q64562, Q64680, Q6GUQ4, Q6VVW9, Q6VVX0, Q7Z449

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

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
CYP2D6	“down-regulates quantity”	tyramine	“chemical modification”
CYP2D6	“up-regulates quantity”	dopamine	“chemical modification”

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	58
Likely benign	20
Benign	7

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3248109	NC_000022.10:g.(?42519405)(42571594_?)del	Pathogenic

SpliceAI

1620 predictions. Top by Δscore:

Variant	Effect	Δscore
22:42126749:CGGC:C	acceptor_gain	1.0000
22:42126750:GGCCT:G	acceptor_loss	1.0000
22:42126751:GCCT:G	acceptor_loss	1.0000
22:42126753:C:CC	acceptor_gain	1.0000
22:42126753:C:T	acceptor_loss	1.0000
22:42126754:T:A	acceptor_loss	1.0000
22:42126846:GGCAC:G	donor_loss	1.0000
22:42126847:GCAC:G	donor_loss	1.0000
22:42126848:CA:C	donor_loss	1.0000
22:42126850:C:CG	donor_loss	1.0000
22:42126850:CCTG:C	donor_gain	1.0000
22:42126874:T:TA	donor_gain	1.0000
22:42126988:GTTCC:G	acceptor_gain	1.0000
22:42126989:TTCC:T	acceptor_gain	1.0000
22:42126990:TCC:T	acceptor_gain	1.0000
22:42126990:TCCC:T	acceptor_loss	1.0000
22:42126991:CC:C	acceptor_gain	1.0000
22:42126991:CCC:C	acceptor_gain	1.0000
22:42126992:CC:C	acceptor_gain	1.0000
22:42126992:CCTGG:C	acceptor_loss	1.0000
22:42126993:C:CC	acceptor_gain	1.0000
22:42126993:C:T	acceptor_gain	1.0000
22:42126994:T:A	acceptor_loss	1.0000
22:42126998:C:CT	acceptor_gain	1.0000
22:42127441:GCCTA:G	donor_loss	1.0000
22:42127442:CCTAC:C	donor_loss	1.0000
22:42127443:CTA:C	donor_loss	1.0000
22:42127444:TACCT:T	donor_loss	1.0000
22:42127445:ACCTT:A	donor_loss	1.0000
22:42127472:T:TA	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000449759 (22:42131812 G>A), RS1000790874 (22:42132252 C>T), RS1001005085 (22:42130885 G>A,C,T), RS1001296663 (22:42127502 C>G,T), RS1001630133 (22:42132489 C>T), RS1002182123 (22:42126570 C>A,G,T), RS1002703132 (22:42126208 G>A), RS1005906316 (22:42132696 G>A,C), RS1006143072 (22:42128630 CCCT>C), RS1007008240 (22:42131407 A>G,T), RS1008010883 (22:42130279 C>G), RS1008147170 (22:42127019 G>T), RS1009016970 (22:42129510 C>A,G,T), RS1009063581 (22:42132232 A>G), RS1009883497 (22:42127068 G>A,T)

Disease associations

OMIM: gene MIM:124030 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): congenital portosystemic shunt (MONDO:0018811)

Orphanet (1): Congenital portosystemic shunt (Orphanet:480531)

HPO phenotypes

3 total (3 of 3 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001939	Abnormality of metabolism/homeostasis
HP:0002664	Neoplasm

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST002539_95	Schizophrenia	2.000000e-09
GCST002549_12	Response to serotonin reuptake inhibitors in major depressive disorder (plasma drug and metabolite levels)	2.000000e-16
GCST002549_13	Response to serotonin reuptake inhibitors in major depressive disorder (plasma drug and metabolite levels)	8.000000e-16
GCST004364_23	Intelligence	3.000000e-10
GCST004364_5	Intelligence	3.000000e-10
GCST004521_160	Autism spectrum disorder or schizophrenia	3.000000e-08
GCST004521_244	Autism spectrum disorder or schizophrenia	4.000000e-09
GCST006803_13	Schizophrenia	2.000000e-14
GCST009600_11	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	1.000000e-08
GCST009733_119	Urinary metabolite levels in chronic kidney disease	6.000000e-16
GCST010002_83	Refractive error	2.000000e-27

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005658	response to selective serotonin reuptake inhibitor
EFO:0004337	intelligence
EFO:0005116	urinary metabolite measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL289 (SINGLE PROTEIN), CHEMBL4523986 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

436 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 506,937 (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
CHEMBL1002	LEVOSALBUTAMOL	4	27,028
CHEMBL1018	DIENESTROL	4	5,607
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL107	COLCHICINE	4	93,932
CHEMBL1086	DIBUCAINE	4	17,231
CHEMBL1089	PHENELZINE	4	18,793
CHEMBL1094	FELBAMATE	4	10,652
CHEMBL1095292	BRETYLIUM TOSYLATE	4	3,061
CHEMBL11	IMIPRAMINE	4	48,893
CHEMBL110	BENZNIDAZOLE	4	3,668
CHEMBL1108	DROPERIDOL	4	16,888
CHEMBL1113	AMOXAPINE	4	20,128
CHEMBL1123	DICYCLOMINE	4	8,691
CHEMBL1175	DULOXETINE	4	28,527
CHEMBL118	CELECOXIB	4	112,844
CHEMBL1180725	PROPANTHELINE	4	5,428
CHEMBL1195	PROPOXYCAINE	4	5,653
CHEMBL1196	PROPARACAINE	4	12,973
CHEMBL1200	BENOXINATE	4	6,712
CHEMBL1200326	NICARDIPINE HYDROCHLORIDE	4	3,903
CHEMBL1200396	BUPIVACAINE HYDROCHLORIDE	4
CHEMBL1200406	DIMENHYDRINATE	4
CHEMBL1200413	TETRAHYDROZOLINE HYDROCHLORIDE	4
CHEMBL1200560	GUANABENZ ACETATE	4
CHEMBL1200873	PHENTOLAMINE MESYLATE	4
CHEMBL1200901	HALOFANTRINE HYDROCHLORIDE	4
CHEMBL1201039	BENZTHIAZIDE	4
CHEMBL1201155	LOXAPINE SUCCINATE	4
CHEMBL1201193	LEVOBUPIVACAINE	4
CHEMBL1201217	DYCLONINE	4

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

PharmGKB clinical annotations

120 annotations.

Variant	Type	Level	Drugs	Phenotypes
CYP2D61, CYP2D610	Dosage	3	fentanyl
CYP2D61, CYP2D610	Efficacy	3	propafenone	Cardiac rhythm disease
CYP2D61, CYP2D610	Metabolism/PK	3	berberine;coptisine
CYP2D61, CYP2D610	Other	4	propranolol
CYP2D61, CYP2D610, CYP2D6*41	Metabolism/PK	3	brexpiprazole
CYP2D61, CYP2D610, CYP2D687, CYP2D688, CYP2D689, CYP2D690, CYP2D691, CYP2D692, CYP2D693, CYP2D694, CYP2D695, CYP2D696, CYP2D697, CYP2D698	Metabolism/PK	3	tolterodine
CYP2D61, CYP2D610, CYP2D687, CYP2D688, CYP2D689, CYP2D690, CYP2D691, CYP2D693, CYP2D694, CYP2D695, CYP2D697, CYP2D698	Metabolism/PK	3	dapoxetine
CYP2D61, CYP2D61xN	Efficacy	4	dolasetron;granisetron	Postoperative Nausea and Vomiting
CYP2D61, CYP2D61xN, CYP2D6*2xN	Efficacy	1A	tropisetron	Vomiting
CYP2D61, CYP2D61xN, CYP2D6*2xN	Efficacy	3	citalopram
CYP2D61, CYP2D61xN, CYP2D62xN, CYP2D63, CYP2D64, CYP2D65, CYP2D69, CYP2D610, CYP2D635, CYP2D635xN, CYP2D6*41	Metabolism/PK	1A	doxepin
CYP2D61, CYP2D61xN, CYP2D62xN, CYP2D63, CYP2D64, CYP2D66	Dosage	3	methadone	Heroin Dependence;Opioid-Related Disorders
CYP2D61, CYP2D61xN, CYP2D62xN, CYP2D64, CYP2D6*5	Dosage	1A	imipramine	Depressive Disorder
CYP2D61, CYP2D61xN, CYP2D62, CYP2D62xN	Toxicity	1A	codeine	Pain
CYP2D61, CYP2D61xN, CYP2D62, CYP2D62xN	Toxicity	1A	tramadol	Cardiotoxicity;Drug Toxicity
CYP2D61, CYP2D61xN, CYP2D62, CYP2D62xN, CYP2D63, CYP2D64, CYP2D65, CYP2D66, CYP2D610, CYP2D617	Metabolism/PK	1A	nortriptyline	Major Depressive Disorder
CYP2D61, CYP2D61xN, CYP2D62, CYP2D62xN, CYP2D63, CYP2D64, CYP2D65, CYP2D66, CYP2D610, CYP2D617, CYP2D629, CYP2D636, CYP2D6*41	Metabolism/PK	1A	codeine
CYP2D61, CYP2D61xN, CYP2D62, CYP2D62xN, CYP2D63, CYP2D64, CYP2D65, CYP2D66, CYP2D6*7	Metabolism/PK	2A	oxycodone	Pain
CYP2D61, CYP2D61xN, CYP2D62, CYP2D62xN, CYP2D63, CYP2D64, CYP2D65, CYP2D69, CYP2D610, CYP2D614, CYP2D6*41	Metabolism/PK	1A	paroxetine
CYP2D61, CYP2D61xN, CYP2D62, CYP2D62xN, CYP2D63, CYP2D64, CYP2D6*6	Efficacy	3	methadone	Heroin Dependence;Opioid-Related Disorders
CYP2D61, CYP2D61xN, CYP2D62, CYP2D62xN, CYP2D64, CYP2D65, CYP2D610, CYP2D635xN	Efficacy	1A	ondansetron	Vomiting
CYP2D61, CYP2D61xN, CYP2D62, CYP2D63, CYP2D64, CYP2D65, CYP2D66, CYP2D610, CYP2D6*41	Toxicity	1A	amitriptyline	Depressive Disorder
CYP2D61, CYP2D61xN, CYP2D62, CYP2D63, CYP2D64, CYP2D65, CYP2D66, CYP2D610, CYP2D6*41	Metabolism/PK	1A	amitriptyline	Depressive Disorder;Mental Disorders
CYP2D61, CYP2D61xN, CYP2D62, CYP2D63, CYP2D64, CYP2D65, CYP2D66, CYP2D610, CYP2D6*41	Metabolism/PK	1A	clomipramine	Major Depressive Disorder;Mental Disorders
CYP2D61, CYP2D61xN, CYP2D62, CYP2D63, CYP2D64, CYP2D65, CYP2D66, CYP2D69, CYP2D610, CYP2D617, CYP2D6*41	Metabolism/PK	1A	tramadol
CYP2D61, CYP2D61xN, CYP2D63, CYP2D64, CYP2D65, CYP2D66	Metabolism/PK	2A	mirtazapine
CYP2D61, CYP2D61xN, CYP2D63, CYP2D64, CYP2D65, CYP2D66	Other	3	donepezil	Alzheimer Disease
CYP2D61, CYP2D61xN, CYP2D63, CYP2D64, CYP2D65, CYP2D66, CYP2D610, CYP2D614	Metabolism/PK	1A	risperidone	Psychotic Disorder;Schizophrenia
CYP2D61, CYP2D61xN, CYP2D63, CYP2D64, CYP2D65, CYP2D66, CYP2D610, CYP2D617	Metabolism/PK	3	fluoxetine	Major Depressive Disorder;Mental Disorders
CYP2D61, CYP2D61xN, CYP2D63, CYP2D64, CYP2D65, CYP2D66, CYP2D6*41	Metabolism/PK	3	galantamine	Dementia
CYP2D61, CYP2D61xN, CYP2D63, CYP2D64, CYP2D6*6	Metabolism/PK	3	methadone
CYP2D61, CYP2D624	Metabolism/PK	3	codeine;N-desmethyltamoxifen
CYP2D61, CYP2D62xN	Toxicity	3	hydrocodone	Drug Toxicity
CYP2D61, CYP2D62xN, CYP2D63, CYP2D64, CYP2D65, CYP2D66, CYP2D6*10	Metabolism/PK	1A	tropisetron
CYP2D61, CYP2D62, CYP2D610, CYP2D687, CYP2D689, CYP2D690, CYP2D693, CYP2D695, CYP2D697, CYP2D698	Metabolism/PK	4	methadone
CYP2D61, CYP2D62, CYP2D62xN, CYP2D63, CYP2D64, CYP2D64xN, CYP2D65, CYP2D66, CYP2D68, CYP2D69, CYP2D610, CYP2D615, CYP2D617, CYP2D618, CYP2D621, CYP2D629, CYP2D636xN, CYP2D638	Metabolism/PK	2A	debrisoquine
CYP2D61, CYP2D62, CYP2D62xN, CYP2D63, CYP2D64, CYP2D65, CYP2D66, CYP2D67, CYP2D68, CYP2D610, CYP2D611, CYP2D612, CYP2D618, CYP2D635xN, CYP2D641, CYP2D659, CYP2D6*62	Metabolism/PK	3	sparteine
CYP2D61, CYP2D62, CYP2D62xN, CYP2D63, CYP2D64, CYP2D66	Efficacy	4	oxycodone	Pain
CYP2D61, CYP2D62, CYP2D62xN, CYP2D63, CYP2D64, CYP2D66	Toxicity	4	oxycodone	CNS depression;Drug Toxicity
CYP2D61, CYP2D62, CYP2D62xN, CYP2D64, CYP2D65, CYP2D66, CYP2D69, CYP2D610	Metabolism/PK	1A	desipramine	Major Depressive Disorder;Mental Disorders

PharmGKB variants

112 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs16947	CYP2D6	3	2.00	94	timolol
rs769258	CYP2D6		0.00	3
rs1058164	CYP2D6		0.00	62
rs1065852	CYP2D6	3	2.00	97	opioids;iloperidone;escitalopram
rs1080983	CYP2D6		0.00	0
rs1080985	CYP2D6	3	1.75	2	debrisoquine;thioridazine
rs1080989	CYP2D6		0.00	0
rs1135822	CYP2D6		0.00	7
rs1135823	CYP2D6		0.00	7
rs1135824	CYP2D6		0.00	53
rs1135840	CYP2D6		0.00	99
rs1985842	CYP2D6		0.00	0
rs2004511	CYP2D6		0.00	0
rs3892097	CYP2D6	3	2.25	75	metoprolol
rs5030655	CYP2D6	3	3.50	43	antipsychotics;metoprolol
rs5030656	CYP2D6		0.00	10
rs5030862	CYP2D6		0.00	4
rs5030865	CYP2D6		0.00	10
rs5030867	CYP2D6		0.00	7
rs28360521	CYP2D6	3	0.00	1	aspirin
rs28371696	CYP2D6		0.00	4
rs28371699	CYP2D6		0.00	0
rs28371702	CYP2D6		0.00	0
rs28371703	CYP2D6		0.00	74
rs28371704	CYP2D6		0.00	74
rs28371706	CYP2D6	3	1.50	21	nevirapine
rs28371710	CYP2D6		0.00	5
rs28371717	CYP2D6		0.00	1
rs28371725	CYP2D6		0.00	27
rs28371726	CYP2D6		0.00	0
rs28371738	CYP2D6		0.00	0
rs35742686	CYP2D6		0.00	53
rs59421388	CYP2D6		0.00	8
rs61736512	CYP2D6		0.00	8
rs72549346	CYP2D6		0.00	1
rs72549348	CYP2D6		0.00	3
rs72549349	CYP2D6		0.00	1
rs72549351	CYP2D6		0.00	1
rs72549354	CYP2D6		0.00	0
rs72549358	CYP2D6		0.00	1

PharmGKB dosing guidelines

69 guidelines.

Source	Drug	Guideline	Dosing?	Recommendation?
CPIC	acebutolol;betaxolol;bisoprolol;carvedilol;nebivolol;propranolol	Annotation of CPIC Guideline for acebutolol, betaxolol, bisoprolol, carvedilol, nebivolol, propranolol and CYP2D6
CPIC	amitriptyline	Annotation of CPIC Guideline for amitriptyline and CYP2C19, CYP2D6	yes	yes
CPIC	atomoxetine	Annotation of CPIC Guideline for atomoxetine and CYP2D6	yes	yes
CPIC	clomipramine	Annotation of CPIC Guideline for clomipramine and CYP2C19, CYP2D6	yes	yes
CPIC	codeine	Annotation of CPIC Guideline for codeine and CYP2D6		yes
CPIC	desipramine	Annotation of CPIC Guideline for desipramine and CYP2D6	yes	yes
CPIC	doxepin	Annotation of CPIC Guideline for doxepin and CYP2C19, CYP2D6	yes	yes
CPIC	duloxetine	Annotation of CPIC Guideline for duloxetine and CYP2D6
CPIC	fluoxetine	Annotation of CPIC Guideline for fluoxetine and CYP2D6
CPIC	fluvoxamine	Annotation of CPIC Guideline for fluvoxamine and CYP2D6	yes	yes
CPIC	hydrocodone	Annotation of CPIC Guideline for hydrocodone and CYP2D6		yes
CPIC	imipramine	Annotation of CPIC Guideline for imipramine and CYP2C19, CYP2D6	yes	yes
CPIC	methadone;oxycodone	Annotation of CPIC Guideline for methadone, oxycodone and COMT, CYP2D6, OPRM1
CPIC	metoprolol	Annotation of CPIC Guideline for metoprolol and CYP2D6		yes
CPIC	nortriptyline	Annotation of CPIC Guideline for nortriptyline and CYP2D6	yes	yes
CPIC	ondansetron	Annotation of CPIC Guideline for ondansetron and CYP2D6		yes
CPIC	paroxetine	Annotation of CPIC Guideline for paroxetine and CYP2D6	yes	yes
CPIC	tamoxifen	Annotation of CPIC Guideline for tamoxifen and CYP2D6	yes	yes
CPIC	tramadol	Annotation of CPIC Guideline for tramadol and CYP2D6		yes
CPIC	trimipramine	Annotation of CPIC Guideline for trimipramine and CYP2C19, CYP2D6	yes	yes
CPIC	tropisetron	Annotation of CPIC Guideline for tropisetron and CYP2D6		yes
CPIC	venlafaxine	Annotation of CPIC Guideline for venlafaxine and CYP2D6		yes
CPIC	vortioxetine	Annotation of CPIC Guideline for vortioxetine and CYP2D6	yes	yes
DPWG	amiodarone	Annotation of DPWG Guideline for amiodarone and CYP2D6
DPWG	amitriptyline	Annotation of DPWG Guideline for amitriptyline and CYP2D6	yes	yes
DPWG	aripiprazole	Annotation of DPWG Guideline for aripiprazole and CYP2D6	yes	yes
DPWG	atenolol	Annotation of DPWG Guideline for atenolol and CYP2D6
DPWG	atomoxetine	Annotation of DPWG Guideline for atomoxetine and CYP2D6	yes	yes
DPWG	bisoprolol	Annotation of DPWG Guideline for bisoprolol and CYP2D6
DPWG	brexpiprazole	Annotation of DPWG Guideline for brexpiprazole and CYP2D6	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 (5 total), top 5:

Ligand	Action	Affinity	Parameter
ajmalicine	Inhibition	8.48	pKi
TIQ-15	Inhibition	6.49	pIC50
compound 46c [PMID: 29350534]	Inhibition	5.58	pIC50
berberine	Inhibition	5.4	pIC50
polyphyllin H	Competitive	5.17	pKi

Binding affinities (BindingDB)

279 measured of 514 human assays (515 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
6-[2-[4-[(4-bromo-3-hydroxyphenyl)methyl]piperidin-1-yl]ethyl]chromen-4-one	KI	0.27 nM	US-8778970: Benzyl piperidine compound
N-[3-[(4aR,6S,8aS)-2-amino-6-methyl-4a,5,6,8-tetrahydro-4H-pyrano[3,4-d][1,3]thiazin-8a-yl]-4-fluorophenyl]-5-chloropyridine-2-carboxamide	IC50	1 nM	US-9744173: 2-amino 6-methyl-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl-1,3-thiazol-4-yl amides
(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
6-[2-[4-[(4-bromo-3-hydroxyphenyl)methyl]piperidin-1-yl]ethyl]-3-hydroxy-2,3-dihydrochromen-4-one	KI	1.1 nM	US-8778970: Benzyl piperidine compound
6-[2-[4-[(4-bromo-3-hydroxyphenyl)methyl]piperidin-1-yl]ethyl]-2,3-dihydrochromen-4-one	KI	1.3 nM	US-8778970: Benzyl piperidine compound
(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
6-[2-[4-[[4-bromo-3-(2-methoxyethoxy)phenyl]methyl]piperidin-1-yl]ethyl]chromen-4-one;hydrochloride	KI	2 nM	US-8778970: Benzyl piperidine compound
(2S)-2-(methylamino)-N-[6-[2-(1-methylisoquinolin-6-yl)ethynyl]-5-[7-methyl-2-(2-methyl-3-pyridinyl)imidazo[1,2-a]pyridin-3-yl]-2-pyridinyl]propanamide	IC50	2 nM	US-9481673: 6-alkynyl-pyridine derivatives
(2S)-2-(methylamino)-N-[5-[7-methyl-2-(2-methylpyrimidin-5-yl)imidazo[1,2-a]pyridin-3-yl]-6-[2-(1-methyl-2-oxoquinolin-6-yl)ethynyl]-2-pyridinyl]propanamide	IC50	2 nM	US-9481673: 6-alkynyl-pyridine derivatives
(2S)-N-[5-[7-chloro-2-(2-methoxy-3-pyridinyl)imidazo[1,2-a]pyridin-3-yl]-6-[2-(1-methylisoquinolin-6-yl)ethynyl]-2-pyridinyl]-2-(methylamino)propanamide	IC50	2 nM	US-9481673: 6-alkynyl-pyridine derivatives
(2S)-N-[5-[2-(2-methoxy-3-pyridinyl)imidazo[1,2-a]pyridin-3-yl]-6-[2-(1-methylisoquinolin-6-yl)ethynyl]-2-pyridinyl]-2-(methylamino)propanamide	IC50	2 nM	US-9481673: 6-alkynyl-pyridine derivatives
6-[2-[4-[[4-bromo-3-(2-hydroxyethoxy)phenyl]methyl]piperidin-1-yl]ethyl]chromen-4-one;hydrochloride	KI	2.1 nM	US-8778970: Benzyl piperidine compound
6-[2-[4-[[4-bromo-3-(2-methoxyethoxy)phenyl]methyl]piperidin-1-yl]ethyl]-3-hydroxychromen-4-one	KI	2.5 nM	US-8778970: Benzyl piperidine compound
N-[3-[(4aR,6S,8aS)-2-amino-6-methyl-4a,5,6,8-tetrahydro-4H-pyrano[3,4-d][1,3]thiazin-8a-yl]-4-fluorophenyl]-5-(difluoromethoxy)pyridine-2-carboxamide	IC50	3 nM	US-9605007: 2-amino-6-methyl-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl-1,3-thiazol-4-yl amides
BAY 59-7939 Analog 18	IC50	4.2 nM	US-8822458: Substituted oxazolidinones and their use in the field of blood coagulation
6-[2-[4-[[4-bromo-3-(2-hydroxyethoxy)phenyl]methyl]piperidin-1-yl]ethyl]-3-hydroxy-2,3-dihydrochromen-4-one	KI	5.5 nM	US-8778970: Benzyl piperidine compound
N-[3-[(4aR,6R,8aS)-2-amino-6-(trifluoromethyl)-4a,5,6,8-tetrahydro-4H-pyrano[3,4-d][1,3]thiazin-8a-yl]-4-fluorophenyl]-5-(difluoromethoxy)pyridine-2-carboxamide	IC50	6 nM	US-9744173: 2-amino 6-methyl-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl-1,3-thiazol-4-yl amides
6-[2-[4-[[4-bromo-3-(2-methoxyethoxy)phenyl]methyl]piperidin-1-yl]ethyl]-3-hydroxy-2,3-dihydrochromen-4-one;hydrochloride	KI	7.4 nM	US-8778970: Benzyl piperidine compound
6-[2-[4-[(4-bromo-3-hydroxyphenyl)methyl]piperidin-1-yl]ethyl]-3,4-dihydro-2H-chromen-4-ol	KI	8.5 nM	US-8778970: Benzyl piperidine compound
(S)-[(5R)-5-ethenyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxyquinolin-4-yl)methanol	IC50	9 nM	US-9173935: Phospholipid drug analogs
N-[3-[(4aR,8aS)-2-amino-4a,5,6,8-tetrahydro-4H-pyrano[3,4-d][1,3]thiazin-8a-yl]-4-fluorophenyl]-5-(difluoromethoxy)pyridine-2-carboxamide	IC50	9 nM	US-9315520: 2-amino-6-methyl-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl-1,3-thiazol-4-yl amides
benzenesulfinate;6-[2-[4-[[4-bromo-3-(2-methoxyethoxy)phenyl]methyl]piperidin-1-yl]ethyl]-3,4-dihydro-2H-chromen-4-ol	KI	12 nM	US-8778970: Benzyl piperidine compound
6-[2-[4-[[4-bromo-3-(2-methoxyethoxy)phenyl]methyl]piperidin-1-yl]-1-hydroxyethyl]-2,3-dihydrochromen-4-one;hydrochloride	KI	17 nM	US-8778970: Benzyl piperidine compound
N-{2-[(4a R, 6S,8aR)-2-Amino-6-methyl-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl]-1,3-thiazol-4-yl}-5-chloropyridine-2-carboxamide	IC50	19 nM	US-9744173: 2-amino 6-methyl-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl-1,3-thiazol-4-yl amides
4-[4-[2-hydroxy-6-(3-hydroxyphenyl)naphthalen-1-yl]anilino]-4-oxobutanoic acid	IC50	20 nM	US-8546392: 17Beta-hydroxysteroid dehydrogenase type 1 inhibitors for the treatment of hormone-related diseases
N-[2-[(4aR,6S,8aR)-2-amino-6-methyl-4a,5,6,8-tetrahydro-4H-pyrano[3,4-d][1,3]thiazin-8a-yl]-1,3-thiazol-4-yl]-5-(difluoromethoxy)-3-methylpyridine-2-carboxamide	IC50	23 nM	US-9744173: 2-amino 6-methyl-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl-1,3-thiazol-4-yl amides
N-[3-[2-hydroxy-6-(3-hydroxyphenyl)naphthalen-1-yl]phenyl]methanesulfonamide	IC50	23 nM	US-8546392: 17Beta-hydroxysteroid dehydrogenase type 1 inhibitors for the treatment of hormone-related diseases
(1S,2S)-1-(6-chloro-3-pyridinyl)-3-(methylamino)-2-naphthalen-2-ylpropan-1-ol	IC50	27 nM	US-9944618: Inhibiting neurotransmitter reuptake
(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
(E)-3-[3-methoxy-5-(6-methoxynaphthalen-2-yl)phenyl]-N-methylprop-2-enamide	IC50	30 nM	US-8546392: 17Beta-hydroxysteroid dehydrogenase type 1 inhibitors for the treatment of hormone-related diseases
N-{2-[(4aR,6S,8aR)-2-Amino-6-methyl-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl]-1,3-thiazol-4-yl}-5-(difluoromethoxy)pyridine-2-carboxamide	IC50	31 nM	US-9744173: 2-amino 6-methyl-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl-1,3-thiazol-4-yl amides
6-bromo-2-(1-methylpyrazol-4-yl)-7-[4-(pyridin-3-ylmethyl)piperazin-1-yl]-1H-imidazo[4,5-b]pyridine	IC50	32 nM	US-9447092: Pharmaceutically active compounds
6-[2-[4-[[4-bromo-3-(2-hydroxyethoxy)phenyl]methyl]piperidin-1-yl]ethyl]-3,4-dihydro-2H-chromen-4-ol	KI	33 nM	US-8778970: Benzyl piperidine compound
6-[2-[4-[[4-bromo-3-(2-methoxyethoxy)phenyl]methyl]piperidin-1-yl]ethyl]-2-hydroxy-2,3-dihydrochromen-4-one	KI	33 nM	US-8778970: Benzyl piperidine compound
(1R,2S)-1-(3-chloro-4-pyridinyl)-3-(methylamino)-2-naphthalen-2-ylpropan-1-ol	IC50	34 nM	US-9944618: Inhibiting neurotransmitter reuptake
6-chloro-7-[4-[(4-chlorophenyl)methyl]piperazin-1-yl]-2-(1,3-dimethylpyrazol-4-yl)-1H-imidazo[4,5-b]pyridine	IC50	38 nM	US-9447092: Pharmaceutically active compounds
3-[[4-[6-chloro-2-(1,3-dimethylpyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl]piperazin-1-yl]methyl]-1,2,4-oxadiazole	IC50	40 nM	US-9447092: Pharmaceutically active compounds
N-[6-[(4aR,6S,8aS)-2-amino-6-methyl-4a,5,6,8-tetrahydro-4H-pyrano[3,4-d][1,3]thiazin-8a-yl]-5-fluoro-2-pyridinyl]-5-(difluoromethoxy)pyridine-2-carboxamide	IC50	43 nM	US-9605007: 2-amino-6-methyl-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl-1,3-thiazol-4-yl amides
(1R,2S)-2-(3,4-dichlorophenyl)-3-(methylamino)-1-(2-nitrophenyl)propan-1-ol	IC50	43 nM	US-9944618: Inhibiting neurotransmitter reuptake

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
10.35	IC50	0.045	nM	CHEMBL180672
10.00	IC50	0.1	nM	CHEMBL382741
9.23	IC50	0.59	nM	TARANABANT
9.00	Potency	1	nM	CHEMBL1492579
9.00	Potency	1	nM	CHEMBL1361285
8.80	Potency	1.6	nM	CHEMBL1531111
8.73	IC50	1.86	nM	KETOCONAZOLE
8.70	IC50	2	nM	QUINIDINE
8.70	IC50	2	nM	CHEMBL1091778
8.70	Potency	2	nM	RAUWOLFIA SERPENTINA
8.70	AC50	1.995	nM	RAUWOLFIA SERPENTINA
8.60	Potency	2.5	nM	CHEMBL1330614
8.60	Potency	2.5	nM	CHEMBL1377111
8.60	AC50	2.512	nM	CHEMBL1330614
8.59	IC50	2.6	nM	CHEMBL538632
8.52	IC50	3	nM	CHEMBL4857395
8.52	IC50	3	nM	CHEMBL1204009
8.50	AC50	3.162	nM	CHEMBL1450157
8.50	AC50	3.162	nM	CHEMBL1611066
8.48	Ki	3.3	nM	RAUWOLFIA SERPENTINA
8.48	IC50	3.3	nM	QUINIDINE
8.46	Ki	3.5	nM	RAUWOLFIA SERPENTINA
8.40	IC50	4	nM	CHEMBL539650
8.40	Potency	4	nM	CHEMBL1528848
8.34	Ki	4.6	nM	RAUWOLFIA SERPENTINA
8.32	Ki	4.8	nM	PRODIPINE
8.30	AC50	5.012	nM	CHEMBL1598281
8.30	AC50	5.012	nM	CHEMBL1543028
8.26	IC50	5.5	nM	CHEMBL3898132
8.25	AC50	5.623	nM	CHEMBL1301946
8.25	AC50	5.623	nM	CHEMBL1446244
8.25	AC50	5.623	nM	CHEMBL1519083
8.25	AC50	5.623	nM	CHEMBL1464982
8.25	AC50	5.623	nM	CHEMBL1407398
8.25	AC50	5.623	nM	CHEMBL1742034
8.25	AC50	5.623	nM	CHEMBL1519391
8.25	AC50	5.623	nM	CHEMBL1339210
8.24	Ki	5.7	nM	RAUWOLFIA SERPENTINA
8.20	Potency	6.3	nM	CHEMBL473104
8.20	Potency	6.3	nM	CHEMBL292477
8.20	Potency	6.3	nM	CHEMBL1553498
8.20	Potency	6.3	nM	CHEMBL1475200
8.20	Potency	6.3	nM	CHEMBL1514639
8.20	Potency	6.3	nM	BUTACAINE
8.20	Potency	6.3	nM	CHEMBL1395421
8.20	Potency	6.3	nM	CHEMBL106437
8.20	Potency	6.3	nM	CHEMBL1441920
8.20	Potency	6.3	nM	CHEMBL18879
8.20	AC50	6.31	nM	CHEMBL1441920
8.20	AC50	6.31	nM	CHEMBL1514639

PubChem BioAssay actives

847 with measured affinity, of 6100 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-[(2S,3S)-4-(4-chlorophenyl)-3-(3-cyanophenyl)butan-2-yl]-2-methyl-2-[[5-(trifluoromethyl)-2-pyridinyl]oxy]propanamide	501996: Inhibition of CYP2D6 in human liver microsomes after 30 mins	ic50	0.0006	uM
N,N-dimethyl-2-[3-[(1S)-1-pyridin-3-ylethyl]-1-benzothiophen-2-yl]ethanamine	473431: Inhibition of recombinant CYP2D6 after 30 mins by fluorescence assay	ic50	0.0020	uM
3-[3-tert-butylsulfanyl-5-(pyridin-2-ylmethoxy)-1-[(4-pyridin-3-ylphenyl)methyl]indol-2-yl]-2,2-dimethylpropanoic acid	432015: Inhibition of CYP2D6	ic50	0.0026	uM
5-(cyclopropylmethylsulfonyl)-2-formyl-N-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-1,3-dihydroisoindole-1-carboxamide	1773709: Inhibition of CYP2D6 in human liver microsomes	ic50	0.0030	uM
3-[3-tert-butylsulfanyl-5-(pyridin-2-ylmethoxy)-1-[[4-(1,3-thiazol-2-yl)phenyl]methyl]indol-2-yl]-2,2-dimethylpropanoic acid	432015: Inhibition of CYP2D6	ic50	0.0040	uM
N-butyl-5H-pyrido[4,3-b]indol-1-amine	348757: Inhibition of CYP2D6	ic50	0.0079	uM
N-(naphthalen-2-ylmethyl)-N-phenylazetidin-3-amine;hydrochloride	1164254: Inhibition of human recombinant CYP2D6 incubated for 5 mins by fluorescence assay	ic50	0.0100	uM
2-acetyl-5-(cyclopropylmethylsulfonyl)-N-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-1,3-dihydroisoindole-1-carboxamide	1773709: Inhibition of CYP2D6 in human liver microsomes	ic50	0.0100	uM
N-methyl-1-[(2S,4R)-4-[4-(trifluoromethoxy)phenyl]-1-[[2-(trifluoromethoxy)phenyl]methyl]azetidin-2-yl]methanamine	2034773: Inhibition of CYP2D6 in human liver microsomes preincubated for 30 mins followed by NADPH addition by LC/MS/MS analysis	ic50	0.0100	uM
5-(cyclopropylmethylsulfonyl)-N-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-2-(2-methoxyacetyl)-1,3-dihydroisoindole-1-carboxamide	1773709: Inhibition of CYP2D6 in human liver microsomes	ic50	0.0120	uM
methyl (1S,15R,16R,20S)-16-methyl-17-oxa-3,13-diazapentacyclo[11.8.0.02,10.04,9.015,20]henicosa-2(10),4,6,8,18-pentaene-19-carboxylate	125789: Inhibitory effect on Bufuralol 1’-hydroxylation by human liver microsomes (Ki = apparent inhibition constant)	ki	0.0170	uM
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-pyridin-3-yl-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	1906671: Inhibition of CYP2D6 in human liver microsomes using bufuralol as substrate incubated for 10 mins in presence of NADPH by LC-MS/MS analysis	ic50	0.0190	uM
N-[(4-chlorophenyl)methyl]-N-(2-fluorophenyl)azetidin-3-amine	1164254: Inhibition of human recombinant CYP2D6 incubated for 5 mins by fluorescence assay	ic50	0.0200	uM
N-[2-[[(1S,2R,4R)-4-[methyl(propan-2-yl)amino]-2-(2-phenylethyl)cyclohexyl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide	1226290: Inhibition of CYP2D6 (unknown origin)	ic50	0.0200	uM
2-acetyl-5-(cyclopropylsulfamoyl)-N-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-1,3-dihydroisoindole-1-carboxamide	1773709: Inhibition of CYP2D6 in human liver microsomes	ic50	0.0200	uM
(2S)-2-[(4-fluoro-3,5-dimethylphenyl)methyl]-6-[(4-fluorophenyl)methylamino]-N-hydroxyhexanamide	654270: Inhibition of CYP2D6	ic50	0.0200	uM
N-[8-[(6-fluoronaphthalen-2-yl)methyl]-8-azabicyclo[3.2.1]octan-3-yl]-2-phenylbenzamide	430102: Inhibition of CYP2D6	ic50	0.0200	uM
N-[3-[[4-[1-tert-butyl-3-(3-hydroxyphenyl)pyrazol-4-yl]-2-pyridinyl]amino]propyl]-4-methoxybenzenesulfonamide	2142027: Inhibition of CYP2D6 (unknown origin) using vivid EOMCC as substrate	ic50	0.0267	uM
(Z)-2-methyl-N’-[[(3R)-1,2,3,4-tetrahydroisoquinolin-3-yl]methyl]-N’-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]but-2-ene-1,4-diamine	1350217: Inhibition of recombinant human CYP2D6 expressed in insect microsomes using AMMC as substrate preincubated for 30 mins followed by NADPH addition measured after 45 mins by fluorescence assay	ic50	0.0270	uM
6,8-dimethoxy-1,3-dimethyl-2-(4-methylphenyl)isoquinolin-2-ium tetrafluoroborate	367399: Inhibition of human CYP2D6 by Lineweaver-Burke plot	ki	0.0281	uM
(1R,2S,5S,8R,9R,10S,11R,18R)-10,18-dihydroxy-12,12-dimethyl-6-methylidene-9-(1,3-thiazol-5-ylmethoxy)-17-oxapentacyclo[7.6.2.15,8.01,11.02,8]octadec-14-en-7-one	2072306: Inhibition of CYP2D6 (unknown origin) using dextromethorphan as substrate preincubated for 5 min followed by NADPH addition and measured after 15 mins	ic50	0.0292	uM
1-(3-acetylphenyl)-3-[(1R,2S)-2-[[(3S)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]methyl]cyclohexyl]urea	310950: Inhibition of human recombinant CYP2D6	ic50	0.0300	uM
1-[(1R,2S)-2-[[(3S)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]methyl]cyclohexyl]-3-[3-(1-methyltetrazol-5-yl)phenyl]urea	412223: Inhibition of CYP2D6	ic50	0.0300	uM
1-[[1-(1H-indol-3-yl)-2-methylpropan-2-yl]amino]-3-phenoxypropan-2-ol	241889: Inhibitory activity against recombinant human Cytochrome P450 2D6 (CYP2D6) after incubated for 45 minutes	ic50	0.0300	uM
(8S)-N-[2-[(3S)-piperidin-3-yl]ethyl]-N-[[(3R)-1,2,3,4-tetrahydroisoquinolin-3-yl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine	1354906: Inhibition of recombinant human CYP2D6 expressed in insect cell microsomes using AMMC as substrate pretreated for 30 mins followed by NADPH addition measured after 45 mins by fluorescence assay	ic50	0.0300	uM
1-[4-chloro-3-(difluoromethoxy)phenyl]-4-(imidazol-1-ylmethyl)triazole	1967564: Inhibition of CYP2D6 in human liver microsomes incubated for 10 mins by LC-MS/MS analysis	ic50	0.0300	uM
1-[[1-(1H-indol-3-yl)-2-methylpropan-2-yl]amino]-3-naphthalen-1-yloxypropan-2-ol	241889: Inhibitory activity against recombinant human Cytochrome P450 2D6 (CYP2D6) after incubated for 45 minutes	ic50	0.0300	uM
(8S)-N-[[3-(aminomethyl)phenyl]methyl]-N-[[(3R)-1,2,3,4-tetrahydroisoquinolin-3-yl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine	1489787: Inhibition of recombinant human CYP2D6 expressed in microsomes of insect cells using AMMC as substrate preincubated for 30 mins followed by NADP addition after 45 mins by fluorescence analysis	ic50	0.0320	uM
8-imidazol-1-yl-5,6,7,8-tetrahydroquinoline	2022035: Inhibition of CYP450 (unknown origin)	ic50	0.0335	uM
2-[2-hydroxy-3-[[1-(4-methoxyphenyl)-2-methylpropan-2-yl]amino]propoxy]benzonitrile	372008: Binding affinity to CYP2D6	ic50	0.0360	uM
2-[[(2R)-1-[4-[4-[3-(azepan-1-yl)propoxy]phenyl]butyl]pyrrolidin-2-yl]methyl]-4-[(4-chlorophenyl)methyl]phthalazin-1-one	591568: Inhibition of CYP2D6	ic50	0.0400	uM
1-(1-cyclohexyl-3,4-dihydro-1H-isoquinolin-2-yl)-2-[[(2S)-1-hydroxy-4-methylpentan-2-yl]amino]ethanone	1238164: Inhibition of CYP2D6 (unknown origin) by fluorescence-based assay	ic50	0.0440	uM
N-methyl-2-phenyl-N-[(1S)-1-phenyl-2-pyrrolidin-1-ylethyl]acetamide	241920: Inhibition of cytochrome P450 2D6 was determined using MAMC (7-methoxy-4-aminomethyl-coumarin) as substrate	ic50	0.0460	uM
(8S)-N-[[4-(aminomethyl)phenyl]methyl]-N-[[(3R)-1,2,3,4-tetrahydroisoquinolin-3-yl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine	1489787: Inhibition of recombinant human CYP2D6 expressed in microsomes of insect cells using AMMC as substrate preincubated for 30 mins followed by NADP addition after 45 mins by fluorescence analysis	ic50	0.0480	uM
5-[3-[2-(trifluoromethyl)phenyl]phenyl]-1H-imidazole	502850: Inhibition of CYP2D6	ic50	0.0500	uM
2-[[6-(benzenesulfonyl)-1,2,3,4-tetrahydronaphthalen-1-yl]methyl]guanidine	484647: Inhibition of CYP2D6	ic50	0.0500	uM
2-[2-hydroxy-3-[[1-(5-methoxy-1H-indol-3-yl)-2-methylpropan-2-yl]amino]propoxy]benzonitrile	241889: Inhibitory activity against recombinant human Cytochrome P450 2D6 (CYP2D6) after incubated for 45 minutes	ic50	0.0500	uM
2-[3-[[1-(1-benzothiophen-3-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]benzonitrile	241889: Inhibitory activity against recombinant human Cytochrome P450 2D6 (CYP2D6) after incubated for 45 minutes	ic50	0.0500	uM
5-(2-benzylpiperazin-1-yl)-1H-indazole	489766: Inhibition of CYP2D6 by fluorescence based assay	ic50	0.0500	uM
N-cyclopropyl-3-[4-[(2,4-difluorophenyl)methyl]piperazin-1-yl]pyrido[3,4-b]pyrazin-2-amine	1816583: Inhibition of CYP2D6 (unknown origin)	ic50	0.0501	uM
6,8-dimethoxy-1,3-dimethyl-2-(4-propan-2-ylphenyl)isoquinolin-2-ium;2,2,2-trifluoroacetate	367399: Inhibition of human CYP2D6 by Lineweaver-Burke plot	ki	0.0547	uM
(E)-3-fluoro-2-methyl-N’-[[(3R)-1,2,3,4-tetrahydroisoquinolin-3-yl]methyl]-N’-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]but-2-ene-1,4-diamine	1350217: Inhibition of recombinant human CYP2D6 expressed in insect microsomes using AMMC as substrate preincubated for 30 mins followed by NADPH addition measured after 45 mins by fluorescence assay	ic50	0.0590	uM
2-[2-(dimethylamino)ethyl]tetracyclo[9.8.0.03,8.014,19]nonadeca-1(11),3,5,7,12,14,16,18-octaen-2-ol	262947: Inhibition of human CYP2D6 expressed in Escherichia coli JM109	ic50	0.0600	uM
N-(cyclobutylmethyl)-2-phenoxy-N-[(3S)-pyrrolidin-3-yl]benzamide	430254: Inhibition of CYP2D6	ic50	0.0650	uM
1-(1-cyclohexyl-3,4-dihydro-1H-isoquinolin-2-yl)-2-[[(2S)-1-hydroxy-3,3-dimethylbutan-2-yl]amino]ethanone	1238164: Inhibition of CYP2D6 (unknown origin) by fluorescence-based assay	ic50	0.0680	uM
14-methyl-7,9,20,22-tetraoxa-14-azapentacyclo[15.7.0.04,12.06,10.019,23]tetracosa-1(24),4,6(10),11,17,19(23)-hexaen-2-one	1254736: Competitive inhibition of CYP2D6 (unknown origin) using dextromethorphan substrate	ki	0.0780	uM
2-[2-hydroxy-3-[[1-(5-hydroxy-1H-indol-3-yl)-2-methylpropan-2-yl]amino]propoxy]benzonitrile	241889: Inhibitory activity against recombinant human Cytochrome P450 2D6 (CYP2D6) after incubated for 45 minutes	ic50	0.0800	uM
N-(2-aminophenyl)-4-[[[(4S)-4-phenyl-1,3-thiazolidin-2-ylidene]amino]methyl]benzamide	762193: Inhibition of CYP2D6 (unknown origin)	ic50	0.0800	uM
N-[[3-[3-(dimethylamino)propoxy]phenyl]methyl]-4-pyridin-4-ylbenzamide	1531949: Inhibition of C-terminal 4His-tagged CYP2D6 (unknown origin) expressed in Escherichia coli by spectrophotometric analysis	ic50	0.0800	uM
1-[[(2S,4R)-4-[4-(trifluoromethoxy)phenyl]-1-[[2-(trifluoromethoxy)phenyl]methyl]azetidin-2-yl]methyl]pyrrolidine	2034773: Inhibition of CYP2D6 in human liver microsomes preincubated for 30 mins followed by NADPH addition by LC/MS/MS analysis	ic50	0.0800	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Quinidine	increases chemical synthesis, increases hydrolysis, affects response to substance, decreases hydroxylation, decreases metabolic processing (+7 more)	34
Dextromethorphan	increases metabolic processing, decreases methylation, decreases reaction, decreases activity, decreases metabolic processing (+3 more)	33
bufuralol	increases metabolic processing, increases chemical synthesis, increases oxidation, decreases reaction, increases hydroxylation (+2 more)	19
Risperidone	affects metabolic processing, affects response to substance, decreases hydroxylation, decreases metabolic processing, increases metabolic processing (+2 more)	16
Metoprolol	decreases degradation, increases abundance, decreases reaction, increases response to substance, affects response to substance (+4 more)	14
Fluoxetine	decreases metabolic processing, affects metabolic processing, affects response to substance, decreases methylation, decreases reaction (+3 more)	13
Tamoxifen	decreases abundance, increases expression, affects cotreatment, affects abundance, decreases response to substance (+6 more)	13
Tramadol	increases activity, affects response to substance, affects metabolic processing, increases metabolic processing, increases response to substance (+3 more)	12
Paroxetine	decreases abundance, decreases metabolic processing, increases metabolic processing, decreases reaction, increases abundance (+6 more)	12
Codeine	increases metabolic processing, affects metabolic processing, affects response to substance, decreases methylation, increases chemical synthesis (+2 more)	9
Venlafaxine Hydrochloride	affects metabolic processing, affects methylation, affects response to substance, decreases methylation, increases metabolic processing (+1 more)	8
Carvedilol	affects response to substance, increases metabolic processing, affects glucuronidation, affects metabolic processing	8
Debrisoquin	affects metabolic processing, decreases response to substance, increases abundance, increases hydroxylation, increases metabolic processing (+3 more)	7
Plant Extracts	decreases activity, decreases expression, increases expression, affects metabolic processing, decreases reaction	7
Dextrorphan	increases chemical synthesis, increases metabolic processing, affects chemical synthesis, decreases reaction	6
Amitriptyline	decreases activity, increases metabolic processing, affects cotreatment, affects response to substance	5
Clozapine	affects cotreatment, affects response to substance, affects metabolic processing, increases metabolic processing	4
Glutathione	decreases reaction, affects cotreatment, increases abundance, increases hydroxylation, increases activity (+5 more)	4
Propranolol	increases metabolic processing, increases oxidation, affects metabolic processing	4
desethylchloroquine	increases abundance, increases metabolic processing, decreases activity	3
Paliperidone Palmitate	affects abundance	3
Amiodarone	decreases activity, increases expression, affects reaction, increases abundance	3
Amodiaquine	increases metabolic processing, increases abundance, increases chemical synthesis	3
Benzo(a)pyrene	affects methylation, decreases expression, increases expression, increases methylation	3
Chlorpromazine	affects response to substance, decreases response to substance, increases activity, increases metabolic processing, affects cotreatment	3
Ketoconazole	affects cotreatment, affects reaction, increases metabolic processing, decreases reaction, decreases activity	3
Methoxychlor	decreases methylation, decreases activity	3
Morphine	affects chemical synthesis, increases chemical synthesis, increases metabolic processing	3
NADP	affects cotreatment, increases activity, increases glutathionylation, affects reaction, increases metabolic processing (+2 more)	3
Nortriptyline	decreases response to substance, increases hydroxylation, increases metabolic processing, decreases reaction	3

ChEMBL screening assays

3659 unique, capped per target: 3565 admet, 91 binding, 2 functional, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1000513	ADMET	Inhibition of human recombinant CYP2D6 expressed in insect microsomes	Discovery of (R)-4-(8-fluoro-2-oxo-1,2-dihydroquinazolin-3(4H)-yl)-N-(3-(7-methyl-1H-indazol-5-yl)-1-oxo-1-(4-(piperidin-1-yl)piperidin-1-yl)propan-2-yl)piperidine-1-carboxamide (BMS-694153): a potent antagonist of the human calcitonin gene-related peptide receptor for migraine with rapid and efficient intranasal exposure. — J Med Chem
CHEMBL1678449	Binding	Inhibition of human CYP2D6	Discovery, synthesis, and structure-activity relationship development of a series of N-(4-acetamido)phenylpicolinamides as positive allosteric modulators of metabotropic glutamate receptor 4 (mGlu(4)) with CNS exposure in rats. — J Med Chem
CHEMBL1741321	Functional	PUBCHEM_BIOASSAY: Cytochrome panel assay with activity outcomes. (Class of assay: other) Panel member name: p450-cyp2d6 Compounds with AC50 equal or less than 10 uM are considered active	PubChem BioAssay data set

Cellosaurus cell lines

28 cell lines: 13 transformed cell line, 10 spontaneously immortalized cell line, 2 cancer cell line, 2 induced pluripotent stem cell, 1 finite cell line

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

Cellosaurus	Name	Category	Sex
CVCL_7308	GM00946	Transformed cell line	Female
CVCL_7468	GM07521	Transformed cell line	Female
CVCL_7611	GM14660	Transformed cell line	Female
CVCL_B5W2	Hepc/2D6.39	Cancer cell line	Male
CVCL_F0FI	V79MZh2D6*1	Spontaneously immortalized cell line	Male
CVCL_F0FJ	V79MZh2D6*2	Spontaneously immortalized cell line	Male
CVCL_F0FK	V79MZh2D6*9	Spontaneously immortalized cell line	Male
CVCL_F0FL	V79MZh2D6*10	Spontaneously immortalized cell line	Male
CVCL_F0FM	V79MZh2D6*17	Spontaneously immortalized cell line	Male
CVCL_F0FN	V79MZh2D6*1-H	Spontaneously immortalized cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06041906	Not specified	ENROLLING_BY_INVITATION	International Registry of Congenital Portosystemic Shunt (IRCPSS)
NCT07314814	Not specified	NOT_YET_RECRUITING	Genetic Hallmarks of Patients With Congenital Portosystemic Shunts and Portopulmonary Hypertension