N- and S-Oxidation Model of the Flavin-containing Monooxygenases
This poster was presented at the Eighth Joint Sheffield Conference on Chemoinformatics; 17-19 June 2019
Peter Walton, Mario Öeren, Peter Hunt, Matthew Segall
Existing computational models of drug metabolism are heavily focused on predicting oxidation by cytochrome P450 (CYP) enzymes, because of their importance in phase I drug metabolism, reactive metabolite formation, and drug-drug interactions. Due, in part, to the success of these models, new drug candidates are typically well-optimised with respect to CYP metabolism However, novel metabolites are observed due to other, less-studied, enzyme families such as the flavin containing monooxygenases (FMOs) are found in multiple tissues, including the liver, and have five active isoforms (FMO 1-5). In common with CYPs, FMOs are responsible for phase I, oxidative metabolism and catalyse a variety of reaction types, including N- and S-oxidation, demethylation, desulphuration and Bayer-Villiger oxidation.
The objective of this study was to elucidate the reaction mechanism of FMO-mediated oxidation to inform the development of models to predict the metabolism of novel substrates.
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