In Silico Modeling of P450 Substrates, Inhibitors, Activators, and Inducers

Title: In Silico Modeling of P450 Substrates, Inhibitors, Activators, and Inducers

Volume: 14 Issue: 5

Author(s): Robert Kirk DeLisle, Jennifer Otten and Susan Rhodes

Affiliation:

Keywords: Cytochrome P450, molecular modeling, drug metabolism, Substrates, Inhibitors, Activators, Inducers, exogenous small molecules, structural biology

Abstract: Cytochrome P450 enzymes are the predominant mediators of phase I metabolism of exogenous small molecules. As a result of their extensive role in metabolism of xenobiotics, drug compounds, and endogenous compounds, as well as their wide tissue distribution, significant drug discovery resources are spent to avoid interacting with this class of enzymes. Here we review historical and recent in silico modeling of 7 cytochrome P450 enzymes of particular interest, specifically CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. For each we provide a brief biological background including known inhibitors, substrates, and inducers, as well as details of computational modeling efforts and advances in structural biology. We also provide similar details for 3 nuclear receptors known to regulate gene expression of these enzyme families.

Cite this article as:

Kirk DeLisle Robert, Otten Jennifer and Rhodes Susan, In Silico Modeling of P450 Substrates, Inhibitors, Activators, and Inducers, Combinatorial Chemistry & High Throughput Screening 2011; 14 (5) . https://dx.doi.org/10.2174/138620711795508377