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: CYP1A2, CYP2A6, CYP...

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Bibliographic Details
Published in:Drug metabolism reviews 2002-01, Vol.34 (1-2), p.69-82
Main Authors: Lewis, David F. V., Modi, Sandeep, Dickins, Maurice
Format: Article
Language:English
Subjects:
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 Enzyme System - chemistry
Cytochrome P-450 Enzyme System - metabolism
Databases, Factual
Enzyme Inhibitors - chemistry
Enzyme Inhibitors - pharmacology
Humans
Kinetics
Quantitative Structure-Activity Relationship
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Summary: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: CYP1A2, 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.
ISSN:0360-2532
1097-9883
DOI:10.1081/DMR-120001391