title: Substrate SARs in human P450s.
abstract: Drug metabolism is now an integral part of the drug discovery process, and the cytochromes P450 (CYPs) are the most important family of enzymes involved in human drug metabolism. An increased understanding of the properties of the substrates for the major human CYPs is thus highly desirable. This article shows how key characteristics of CYP substrates, such as lipophilicity, molecular mass and hydrogen-bonding potential, govern selectivity towards individual CYPs. Importantly, the variation in binding affinities of 60 human CYP substrates can be explained by understanding the key physicochemical, structural and electronic characteristics that govern substrate binding to each isozyme.
authors.affiliation: School of Biomedical and Life Sciences, University of Surrey, Guildford, Surrey, UK GU2 7XH. d.lewis@surrey.ac.uk
authors.forename: David F V
authors.initials: DF
authors.lastname: Lewis
authors.forename: Maurice
authors.initials: M
authors.lastname: Dickins
mesh_terms: D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry* / Q000145:classification / Q000493:pharmacokinetics*; D006801:Humans; D008658:Inactivation, Metabolic; D013329:Structure-Activity Relationship
chemical_list: D003577:Cytochrome P-450 Enzyme System