Publications and Presentations

Predicting Regioselectivity and Lability of P450 Metabolism

This article describes the underlying methods, validation and example applications of the most recent models of Cytochrome P450 metabolism in StarDrop’s P450 module.

predicting regioselectivity and lability of CYP450 mtabolism


Cytochrome P450s (CYPs) are one of the most important enzyme families involved in drug metabolism. To ensure metabolic stability, reduce the risk of drug-drug interactions and evaluate potential metabolites, it is essential to predict whether and at which atomic sites CYP will metabolise your compound.

In this article, a method for predicting CYP metabolism is introduced. It considers two factors. Firstly, reactivity of each site to metabolism in the context of the molecule is calculated, via semi-empirical quantum mechanical simulations. Secondly, isoform-specific accessibility is considered, using ligand-based models to correct for steric and orientation effects which differ between CYP isoform binding pockets. The resulting models can accurately predict both the relative proportion of metabolite formation and provide an estimation of the activation energy of each site.


Citation details

J. D. Tyzack, P. A. Hunt, and M. D. Segall, J. Chem. Inf. Model. 2016, 56, 11, 2180–2193

DOI: 10.1021/acs.jcim.6b00233


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