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CYP2A6

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Target id: 1321

Nomenclature: CYP2A6

Family: CYP2 family: drug metabolising subset

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 494 19q13.2 CYP2A6 cytochrome P450 family 2 subfamily A member 6
Previous and Unofficial Names Click here for help
Coumarin 7-hydroxylase | cytochrome P450, subfamily IIA (phenobarbital-inducible), polypeptide 6 | 1,4-cineole 2-exo-monooxygenase | CYP2A3 | Cytochrome P450 IIA3 | cytochrome P450, family 2, subfamily A, polypeptide 6
Database Links Click here for help
Alphafold P11509 (Hs)
BRENDA 1.14.14.1
ChEMBL Target CHEMBL5282 (Hs)
Ensembl Gene ENSG00000255974 (Hs)
Entrez Gene 1548 (Hs)
Human Protein Atlas ENSG00000255974 (Hs)
KEGG Enzyme 1.14.14.1
KEGG Gene hsa:1548 (Hs)
Pharos P11509 (Hs)
SynPHARM 82710 (in complex with compound 39a [PMID: 15634016])
UniProtKB P11509 (Hs)
Wikipedia CYP2A6 (Hs)
Enzyme Reaction Click here for help
EC Number: 1.14.14.1
Substrates and Reaction Kinetics Click here for help
Substrate Sp. Property Value Units Standard property Standard value Assay description Assay conditions Comments Reference
nicotine N/A - -
tegafur Hs - -

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Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
compound 38a [PMID: 15634016] Small molecule or natural product Hs Inhibition 7.7 pKi 2
⤷ pKi 7.7 (Ki 2x10-8 M) [2]
compound 39a [PMID: 15634016] Small molecule or natural product Ligand has a PDB structure Hs Inhibition 7.4 pKi 2
⤷ pKi 7.4 (Ki 4x10-8 M) [2]
compound 23 [PMID: 17125252] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.2 pKi 7
⤷ pKi 6.2 (Ki 6x10-7 M) [7]
esculetin Small molecule or natural product Ligand has a PDB structure Hs Inhibition 6.4 pIC50 5
⤷ pIC50 6.4 (IC50 3.9x10-7 M) [5]
Inhibitor Comments
Additional CYP2A6 inhibitors are reported in [6].
General Comments
CYP2A6 is the major nicotine metabolising enzyme and is believed to be involved in the generation of mutagenic tobacco-related nitrosamines [1,3-4]. CYP2A6 inhibiting compounds are of interest to the pharmaceutical industry as these may be useful additional drugs for smoking cessation therapy [6].

References

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1. Benowitz NL. (1988) Drug therapy. Pharmacologic aspects of cigarette smoking and nicotine addition. N Engl J Med, 319 (20): 1318-30. [PMID:3054551]

2. Denton TT, Zhang X, Cashman JR. (2005) 5-substituted, 6-substituted, and unsubstituted 3-heteroaromatic pyridine analogues of nicotine as selective inhibitors of cytochrome P-450 2A6. J Med Chem, 48 (1): 224-39. [PMID:15634016]

3. Hecht SS, Hoffmann D. (1988) Tobacco-specific nitrosamines, an important group of carcinogens in tobacco and tobacco smoke. Carcinogenesis, 9 (6): 875-84. [PMID:3286030]

4. Nakajima M, Kuroiwa Y, Yokoi T. (2002) Interindividual differences in nicotine metabolism and genetic polymorphisms of human CYP2A6. Drug Metab Rev, 34 (4): 865-77. [PMID:12487152]

5. Qi X, Dou T, Wang Z, Wu J, Yang L, Zeng S, Deng M, Lü M, Liang S. (2019) Inhibition of human cytochrome P450 2A6 by 7-hydroxycoumarin analogues: Analysis of the structure-activity relationship and isoform selectivity. Eur J Pharm Sci, 136: 104944. [PMID:31163215]

6. Tani N, Juvonen RO, Raunio H, Fashe M, Leppänen J, Zhao B, Tyndale RF, Rahnasto-Rilla M. (2014) Rational design of novel CYP2A6 inhibitors. Bioorg Med Chem, 22 (23): 6655-64. [PMID:25458499]

7. Yano JK, Denton TT, Cerny MA, Zhang X, Johnson EF, Cashman JR. (2006) Synthetic inhibitors of cytochrome P-450 2A6: inhibitory activity, difference spectra, mechanism of inhibition, and protein cocrystallization. J Med Chem, 49 (24): 6987-7001. [PMID:17125252]

Contributors

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