On the recognition of mammalian microsomal cytochrome P450 substrates and their characteristics: towards the prediction of human p450 substrate specificity and metabolism

Biochem Pharmacol. 2000 Aug 1;60(3):293-306. doi: 10.1016/s0006-2952(00)00335-x.


The characteristics of mammalian microsomal P450 xenobiotic substrates are described, particularly with reference to the major P450 isoforms associated with drug metabolism in humans. It is further reported that a relatively small number of molecular, electronic, and physico-chemical properties are required to discriminate between chemicals that exhibit specificity for human P450 isoforms: CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4. Molecular templates of superimposed substrates are shown to be complementary with the putative active sites of the relevant enzymes, thus enabling a possible prediction of P450 specificity from structure. Factors contributing to metabolic clearance and binding affinity are also discussed, and methods for their calculation are described.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Cytochrome P-450 Enzyme Inhibitors
  • Cytochrome P-450 Enzyme System / metabolism*
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / metabolism
  • Metabolic Clearance Rate
  • Microsomes / enzymology*
  • Models, Chemical
  • Pharmaceutical Preparations / metabolism
  • Structure-Activity Relationship
  • Substrate Specificity


  • Cytochrome P-450 Enzyme Inhibitors
  • Enzyme Inhibitors
  • Isoenzymes
  • Pharmaceutical Preparations
  • Cytochrome P-450 Enzyme System