Modeling Cytochrome P450 (CYP) Liabilities: Predicting CYP Selectivity, Reactivity
Cytochrome P450 oxidases (CYPs) are heme-containing enzymes responsible for clearing xenobiotics, including drug molecules, from the human body via oxidative metabolism. Understanding and predicting how CYPs might modify or otherwise interact with a potential drug is an important step in drug design efforts. Although there are dozens of CYP crystal structures, most existing modeling tools addressing potential CYP liabilities completely neglect this structural information. In this Webinar, we’ll present our methodology that predicts: a) which CYP isoforms are most likely to interact with a user-provided small molecule, b) whether the molecule is predicted to be a CYP inhibitor or a substrate, and c) which part of the small molecule is most likely to be oxidated, i.e., the sites of metabolism (SOM). Because our approach for predicting SOMs directly incorporates CYP structural information, these predictions can be visualized in the context of a CYP pocket, thereby affording the ability to proactively address predicted liabilities in a familiar structure-based design context – a clear improvement over the simple pass/fail metric that many existing methods use.
Airdate: April 20, 2021
