Abstract

Many structure-activity classification models have been published for predicting whether a given compound is likely to inhibit and/or be subject to metabolism by a given cytochrome P450 (CYP) isoform, and several of them are commercially available. Some products predict the sites of metabolism (SoMs), liver microsomal stability, and which metabolites are most likely to be produced. ADMET Predictor™ 8.0 includes substrate classification models for CYPs 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4, as well as models that predict the corresponding isoform-specific SoMs. In addition, models for inhibitor classification and site-specific kinetic parameters (maximal velocity (Vmax), Michaelis-Menten constant (Km), and intrinsic clearance (CLint)) are provided for five of the major hepatic CYPs: 1A2, 2C9, 2C19, 2D6 and 3A4. ADMET Predictor integrates the substrate classification, SoM, and kinetic predictions and presents them in a readily interpretable way that identifies the most likely metabolites and predicts the contribution each will make to CYP metabolism in vivo.

Cambridge Healthtech BioIT World, April 5-7, 2016, Boston, MA

By Robert D. Clark, David Miller, Michael S. Lawless, and Marvin Waldman