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- CYP2 family: drug metabolising subset
CYP2 family: drug metabolising subset C
Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
Overview
CYP1, 2 and 3 family enzymes are involved in the biotransformation of xenobiotics, including clinically used drugs. Polymorphisms, particularly in the CYP2 family, impact upon an individual's response to drugs [31], including the risk of adverse drug reactions, drug efficacy and dose requirement.
Enzymes
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CYP2A6
C
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CYP2A7 C Show summary »« Hide summary
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CYP2A13 C Show summary »« Hide summary
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CYP2B6
C
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CYP2C8
C
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CYP2C9
C
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CYP2C18 Show summary »« Hide summary
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CYP2C19 C Show summary »« Hide summary
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CYP2D6
C
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CYP2E1
C
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CYP2F1 C Show summary »« Hide summary
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CYP2J2 C Show summary »« Hide summary
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References
1. Backman JT, Filppula AM, Niemi M, Neuvonen PJ. (2016) Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions. Pharmacol Rev, 68 (1): 168-241. [PMID:26721703]
2. Bae SH, Kwon MJ, Choi EJ, Zheng YF, Yoon KD, Liu KH, Bae SK. (2013) Potent inhibition of cytochrome P450 2B6 by sibutramine in human liver microsomes. Chem Biol Interact, 205 (1): 11-9. [PMID:23777987]
3. Bertilsson L, Henthorn TK, Sanz E, Tybring G, Säwe J, Villén T. (1989) Importance of genetic factors in the regulation of diazepam metabolism: relationship to S-mephenytoin, but not debrisoquin, hydroxylation phenotype. Clin Pharmacol Ther, 45 (4): 348-55. [PMID:2495208]
4. Boonruang S, Prakobsri K, Pouyfung P, Prasopthum A, Rongnoparut P, Sarapusit S. (2020) Structure-activity relationship and in vitro inhibition of human cytochrome CYP2A6 and CYP2A13 by flavonoids. Xenobiotica, 50 (6): 630-639. [PMID:31578905]
5. Crosignani S, Jorand-Lebrun C, Campbell G, Prêtre A, Grippi-Vallotton T, Quattropani A, Bouscary-Desforges G, Bombrun A, Missotten M, Humbert Y et al.. (2011) Discovery of a Novel Series of CRTH2 (DP2) Receptor Antagonists Devoid of Carboxylic Acids. ACS Med Chem Lett, 2 (12): 938-42. [PMID:24900284]
6. Daly AK, Rettie AE, Fowler DM, Miners JO. (2017) Pharmacogenomics of CYP2C9: Functional and Clinical Considerations. J Pers Med, 8 (1). [PMID:29283396]
7. Desta Z, Zhao X, Shin JG, Flockhart DA. (2002) Clinical significance of the cytochrome P450 2C19 genetic polymorphism. Clin Pharmacokinet, 41 (12): 913-58. [PMID:12222994]
8. Diesinger T, Buko V, Lautwein A, Dvorsky R, Belonovskaya E, Lukivskaya O, Naruta E, Kirko S, Andreev V, Buckert D et al.. (2020) Drug targeting CYP2E1 for the treatment of early-stage alcoholic steatohepatitis. PLoS One, 15 (7): e0235990. [PMID:32701948]
9. Fontana E, Dansette PM, Poli SM. (2005) Cytochrome p450 enzymes mechanism based inhibitors: common sub-structures and reactivity. Curr Drug Metab, 6 (5): 413-54. [PMID:16248836]
10. Foti RS, Rock DA, Han X, Flowers RA, Wienkers LC, Wahlstrom JL. (2012) Ligand-based design of a potent and selective inhibitor of cytochrome P450 2C19. J Med Chem, 55 (3): 1205-14. [PMID:22239545]
11. Fukami T, Nakajima M, Sakai H, McLeod HL, Yokoi T. (2006) CYP2A7 polymorphic alleles confound the genotyping of CYP2A6*4A allele. Pharmacogenomics J, 6 (6): 401-12. [PMID:16636685]
12. Ha-Duong NT, Dijols S, Marques-Soares C, Minoletti C, Dansette PM, Mansuy D. (2001) Synthesis of sulfaphenazole derivatives and their use as inhibitors and tools for comparing the active sites of human liver cytochromes P450 of the 2C subfamily. J Med Chem, 44 (22): 3622-31. [PMID:11606127]
13. Helsby NA, Ward SA, Edwards G, Howells RE, Breckenridge AM. (1990) The pharmacokinetics and activation of proguanil in man: consequences of variability in drug metabolism. Br J Clin Pharmacol, 30 (4): 593-8. [PMID:2291871]
14. Kim HG, Lee HS, Jeon JS, Choi YJ, Choi YJ, Yoo SY, Kim EY, Lee K, Park I, Na M et al.. (2020) Quasi-Irreversible Inhibition of CYP2D6 by Berberine. Pharmaceutics, 12 (10). DOI: 10.3390/pharmaceutics12100916 [PMID:32987920]
15. Lafite P, Dijols S, Buisson D, Macherey AC, Zeldin DC, Dansette PM, Mansuy D. (2006) Design and synthesis of selective, high-affinity inhibitors of human cytochrome P450 2J2. Bioorg Med Chem Lett, 16 (10): 2777-80. [PMID:16495056]
16. Lewis DF, Ito Y, Lake BG. (2009) Molecular modelling of CYP2F substrates: comparison of naphthalene metabolism by human, rat and mouse CYP2F subfamily enzymes. Drug Metabol Drug Interact, 24 (2-4): 229-57. [PMID:20408502]
17. Llerena A, Dorado P, Peñas-Lledó EM. (2009) Pharmacogenetics of debrisoquine and its use as a marker for CYP2D6 hydroxylation capacity. Pharmacogenomics, 10 (1): 17-28. [PMID:19102711]
18. Mahli A, Erwin Thasler W, Hellerbrand C. (2019) Establishment of a p-nitrophenol oxidation-based assay for the analysis of CYP2E1 activity in intact hepatocytes in vitro. Toxicol Mech Methods, 29 (3): 219-223. [PMID:30380359]
19. Miners JO, Smith KJ, Robson RA, McManus ME, Veronese ME, Birkett DJ. (1988) Tolbutamide hydroxylation by human liver microsomes. Kinetic characterisation and relationship to other cytochrome P-450 dependent xenobiotic oxidations. Biochem Pharmacol, 37 (6): 1137-44. [PMID:3355588]
20. Pelkonen O, Rautio A, Raunio H, Pasanen M. (2000) CYP2A6: a human coumarin 7-hydroxylase. Toxicology, 144 (1-3): 139-47. [PMID:10781881]
21. 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]
22. Solanki M, Pointon A, Jones B, Herbert K. (2018) Cytochrome P450 2J2: Potential Role in Drug Metabolism and Cardiotoxicity. Drug Metab Dispos, 46 (8): 1053-1065. [PMID:29695613]
23. Su T, Bao Z, Zhang QY, Smith TJ, Hong JY, Ding X. (2000) Human cytochrome P450 CYP2A13: predominant expression in the respiratory tract and its high efficiency metabolic activation of a tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Cancer Res, 60 (18): 5074-9. [PMID:11016631]
24. Sykes MJ, McKinnon RA, Miners JO. (2008) Prediction of metabolism by cytochrome P450 2C9: alignment and docking studies of a validated database of substrates. J Med Chem, 51 (4): 780-91. [PMID:18237107]
25. Turpeinen M, Zanger UM. (2012) Cytochrome P450 2B6: function, genetics, and clinical relevance. Drug Metabol Drug Interact, 27 (4): 185-97. [PMID:23152403]
26. Walsky RL, Obach RS. (2007) A comparison of 2-phenyl-2-(1-piperidinyl)propane (ppp), 1,1',1''-phosphinothioylidynetrisaziridine (thioTEPA), clopidogrel, and ticlopidine as selective inactivators of human cytochrome P450 2B6. Drug Metab Dispos, 35 (11): 2053-9. [PMID:17682072]
27. Webster SP, McBride A, Binnie M, Sooy K, Seckl JR, Andrew R, Pallin TD, Hunt HJ, Perrior TR, Ruffles VS et al.. (2017) Selection and early clinical evaluation of the brain-penetrant 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor UE2343 (Xanamem™). Br J Pharmacol, 174 (5): 396-408. [PMID:28012176]
28. Wu S, Moomaw CR, Tomer KB, Falck JR, Zeldin DC. (1996) Molecular cloning and expression of CYP2J2, a human cytochrome P450 arachidonic acid epoxygenase highly expressed in heart. J Biol Chem, 271 (7): 3460-8. [PMID:8631948]
29. Wu Z, Lee D, Joo J, Shin JH, Kang W, Oh S, Lee DY, Lee SJ, Yea SS, Lee HS et al.. (2013) CYP2J2 and CYP2C19 are the major enzymes responsible for metabolism of albendazole and fenbendazole in human liver microsomes and recombinant P450 assay systems. Antimicrob Agents Chemother, 57 (11): 5448-56. [PMID:23959307]
30. 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]
31. Zanger UM, Schwab M. (2013) Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol Ther, 138 (1): 103-41. [PMID:23333322]
32. Zeldin DC, DuBois RN, Falck JR, Capdevila JH. (1995) Molecular cloning, expression and characterization of an endogenous human cytochrome P450 arachidonic acid epoxygenase isoform. Arch Biochem Biophys, 322 (1): 76-86. [PMID:7574697]
NC-IUPHAR subcommittee and family contributors
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Kathryn Burns
Nuala Ann Helsby |
How to cite this family page
Database page citation (select format):
Concise Guide to PHARMACOLOGY citation:
Alexander SPH, Fabbro D, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: Enzymes. Br J Pharmacol. 180 Suppl 2:S289-373.
