Comparison and summary of in silico prediction tools for CYP450-mediated drug metabolism

The cytochrome P450 (CYP450) enzyme system is responsi-ble for the metabolism of more than two-thirds of xenobi-otics. This review summarizes reports of a series of in silico tools for CYP450 enzyme-drug interaction predictions, including the prediction of sites of metabolism (SOM) of a drug and the identification of inhibitor/substrates for CYP subtypes. We also evaluated four prediction tools to identify CYP inhibitors utilizing 52 of the most frequently pre-scribed drugs. ADMET Predictor and CYPlebrity demon-strated the best performance. We hope that this review provides guidance for choosing appropriate enzyme predic-tion tools from a variety of in silico platforms to meet individual needs. Such predictions are useful for medicinal chemists to prioritize their designed compounds for further drug discovery.