Quantitative structure-activity relationships for predicting metabolism and modeling cytochrome P450 enzyme activities

Abstract

Quantitative structure-activity relationships (QSARs) for predicting phase I and phase II metabolism and for modeling cytochrome P450 enzyme activities are described and reviewed. Papers dealing with three-dimensional techniques such as comparative molecular field analysis and pharmacophore modeling are included. This review focuses on those cytochrome P450 isoenzymes that are expressed in human hepatocytes and that are commonly responsible for the majority of drug and xenobiotic metabolism. Substrate-type selectivity information for those isoenzymes is included. The importance of lipophilicity correlations in xenobiotic metabolism predictions are outlined. A brief inclusion of available material on the prediction phase II conjugation biotransformations such as glucuronidation, sulfation, glycination, and glutathionation are included. Historical information is briefly discussed, but more detailed reviews are provided for papers published since 1997.