Structure-activity relationship for human cytochrome P450 substrates and inhibitors.
Criteria governing the avidity of substrate binding to human hepatic cytochromes P450 (CYP) associated with Phase 1 metabolism of drugs are described. The results of extensive quantitative structure-activity relationship (QSAR) analyses are reported for substrates of human P450s: CYPIA2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4, representing the enzymes exhibiting major involvement in the metabolism of drug substrates in Homo sapiens. In particular, it is shown that hydrogen bond properties in each class of enzyme-substrate complex are especially important factors in determining substrate binding affinity towards those human P450s which are involved in drug metabolism.
Lewis
David F V
DF
School of Biomedical and Life Sciences, University of Surrey, Guildford, UK. d.lewis@surrey.ac.uk
Modi
Sandeep
S
Dickins
Maurice
M
D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry* / Q000378:metabolism*; D016208:Databases, Factual; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D021281:Quantitative Structure-Activity Relationship
D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System