Publications and Presentations

Predicting Regioselectivity of AO, CYP, FMO and UGT Metabolism Using Quantum Mechanical Simulations and Machine Learning

This paper describes the prediction of the regioselectivity of metabolism by AOs, FMOs and UGTs for humans and CYPs for three preclinical species. The research extends from previous work developing the StarDrop™ P450 module. Visit the P450 webpage to discover how StarDrop can help you model metabolism.

First page of Journal of Medicinal Chemistry article on metabolism prediction


Mario Öeren, Peter J. Walton, James Suri, David J. Ponting, Peter A. Hunt, and Matt D. Segall


Predicting the sites of metabolism for different key enzymes across the various phases of drug metabolism is vital in avoiding the failure of many late-stage drug candidates or even withdrawal of approved drugs. This study presents methods for predicting the isoform-specific metabolism for several key enzymes involved in drug metabolism across both phase I (modification) and II (conjugation). These include human aldehyde oxidases (AOs), flavin-containing monoxygenases (FMOs) and uridine 5′-diphospho-glucuronosyltransferases (UGTs). General models of cytochrome P450 (CYP) metabolism for preclinical species were also developed.

Using semi-empirical quantum mechanical simulations, the reactivity of each site of metabolism is evaluated holistically in the context of the whole molecule. This reactivity information is then combined with the orientation and steric effects of the binding pockets of the different enzyme isoforms, to generate predictive models, achieving excellent balanced accuracy and kappa values.

Citation Details

M. Öeren, P. J. Walton, J. Suri, D. J. Ponting, P. A. Hunt, and M. D. Segall, J. Med. Chem. 2022, 65, 20, 1406–1408.

DOI: 10.1021/acs.jmedchem.2c01303

Find out more

Read the full article on the journal webpage via the button below. If you would like to discover more of our metabolism research, take a look at our recent J. Chem. Inf. Model. paper, which describes how to predict the regioselectivity of SULT metabolism, or watch our webinar, on the integrated prediction of phase I and II metabolism.


Understanding drug metabolism is crucial to avoid late-stage failure of drug candidates. Optibrium is working at the forefront of predictive modelling, constantly bringing out new research and product updates to help you get a better understanding of your compound’s metabolic stability. Register your interest now to be first to know about our latest metabolism prediction research, development and product updates.