Human Cytochromes P450 Associated with the Phase 1 Metabolism of Drugs and other Xenobiotics: A Compilation of Substrates and Inhibitors of the CYP1, CYP2 and CYP3 Families

摘要

Abstract: This review represents a compilation of typical substrates and inhibitors for human cytochromenP450 (CYP) enzymes that are involved in drug metabolism, specifically those from the CYP1, CYP2 and CYP3nfamilies. Relatively recent literature on substrates and inhibitors has been collected and the relevant Km and Kinvalues, respectively, are tabulated. Furthermore, physicochemical properties in the form of lipophilicity (log Pnand log D7.4 values) and acidity/basicity (pKa values) are also tabulated for a significant number of substrates,ntogether with some information on inhibitors, although only key inhibitors have been selected as thenmain focus is on substrates. The collated information indicates that there are certain commonalities betweennsubstrates for the same enzyme, especially with respect to their positions of metabolism and likely interactionsnwith the relevant enzyme active site regions. The compilation therefore assists in establishing substratenstructure-activity relationships (SSARs) within human drug-metabolizing P450s.