Abstract

In the drug discovery cascade, metabolism studies should be performed as early as possible to allow an early evaluation of the metabolism profiles of drug candidates. To help design new drug candidates with improved pharmacokinetics, the knowledge of the site of metabolism is necessary. Computational or in silico metabolism approaches can be broadly classified into (i) ligand-based methods, and (ii) structure-based methods. This review highlight tools used to predict P450-mediated metabolism including ligand-based and structure-based approaches. Some examples of successful application of an integrated in silico approach for the prediction of Phase I metabolism for some flavonoids and lead compounds are presented. Moreover, an integrated in silico approach for the prediction of P450- mediated metabolism is described.

Keywords: Cytochrome P450, docking, drug discovery, ligand-based, metabolism, prediction, structure-based.