Computational approaches for predicting CYP-related metabolism properties in the screening of new drugs

The site of biotransformation, the extent and rate of metabolism and the number of active metabolic pathways are among the most important characteristics of the pharmacokinetics of a drug. The catalytic activity of drug metabolizing enzymes is likely the most influential determinant of the pharmacokinetic variability. Metabolic stability is the prerequisite for sustaining the therapeutically relevant concentrations. Metabolic inhibition and induction can give rise to clinically important drug–drug interactions. A variety of computational approaches are currently available for predicting different cytochrome P450 (CYP)-related metabolism endpoints. The present review will describe these approaches and their impact on drug development process. Indications on the available software for the implementation will also be given. CYP structure and/or ligand structure.