Abstract

Structure activity relationships (SAR), three-dimensional structure activity relationships (3D-QSAR), and pharmacophores represent useful tools in understanding cytochrome P450 (CYP) active sites in the absence of crystal structures for these human enzymes. These approaches have developed over the last 30 years such that they are now being applied in numerous industrial and academic laboratories solely for this purpose. Such computational approaches have helped in understanding substrate and inhibitor binding to the major human CYPs 1A2, 2B6, 2C9, 2D6, 3A4 as well as other CYPs and additionally complement homology models for these enzymes. Similarly, these approaches may assist in our understanding of CYP induction. This review describes in detail the development of pharmacophores and 3D-QSAR techniques, which are now being more widely used for modeling CYPs; the review will also describe how such approaches are likely to further impact our active site knowledge of these omnipresent and important enzymes.