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Pharmacogenomics of the cytochrome P450 2C family: impacts of amino acid variations on drug metabolism

Authors
Type
Published Article
Journal
Drug Discovery Today
Publisher
Elsevier
Publication Date
Feb 16, 2017
Volume
22
Issue
2
Pages
366–376
Identifiers
DOI: 10.1016/j.drudis.2016.09.015
PMID: 27693711
Source
USPC - SET - SVS
License
White

Abstract

Pharmacogenomics investigates DNA and RNA variations in the human genome related to drug responses. Cytochrome P450 (CYP) is a supergene family of drug-metabolizing enzymes responsible for the metabolism of approximately 90% of human drugs. Among the major CYP isoforms, the CYP2C subfamily is of clinical significance because it metabolizes approximately 20% of clinically administrated drugs and represents several variant alleles leading to adverse drug reactions or altering drug efficacy. Here, we review recent progress on understanding the interindividual variability of the CYP2C members and the functional and clinical impact on drug metabolism. We summarize current advances in the molecular modeling of CYP2C polymorphisms and discuss the structural bases and molecular mechanisms of amino acid variants of CYP2C members that affect drug metabolism.

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