Binding of CYP2C9 with Diverse Drugs and its Implications for Metabolic Mechanism

Title: Binding of CYP2C9 with Diverse Drugs and its Implications for Metabolic Mechanism

Volume: 5 Issue: 3

Author(s): Jing-Fang Wang, Jing-Yi Yan, Dong-Qing Wei and Kuo-Chen Chou

Affiliation:

Keywords: CYP2C9, cytochrome P-450, structure-activity relationship, metabolic mechanism

Abstract: Cytochrome P450 2C9 (CYP2C9) is an important member of the cytochrome P450 enzyme superfamily with responsibility for metabolizing many important exogenous and endogenous compounds in many species of microorganisms, plants and animals. CYP2C9 is related to the oxidative of 16% of all therapeutics in current clinical use and has adverse drug effects, such as, enzyme induction and inhibition. In order to understand the metabolic mechanism of various drugs, two crystal structures of CYP2C9 have been studied, and their structural differences and structure-activity relationships with the drugs of Fluoxetine, Ibuprofen, Naproxen, Suprofen, and Mefenamic acid were investigated. By a series of docking studies and MD simulations, the binding pockets of CYP2C9 for the five drugs are explicitly defined that will be very useful for conducting mutagenesis studies, providing insights into the metabolic mechanism, which may be of relevance to the personalized drug.

Cite this article as:

Wang Jing-Fang, Yan Jing-Yi, Wei Dong-Qing and Chou Kuo-Chen, Binding of CYP2C9 with Diverse Drugs and its Implications for Metabolic Mechanism, Medicinal Chemistry 2009; 5 (3) . https://dx.doi.org/10.2174/157340609788185954