In vitro and pharmacophore insights into CYP3A enzymes

Trends Pharmacol Sci. 2003 Apr;24(4):161-6. doi: 10.1016/s0165-6147(03)00049-x.

Abstract

The cytochrome P450 3A (CYP3A) enzymes have a major role in the metabolism of drugs in humans. Their wide substrate specificity and induction by a vast array of structurally diverse compounds presents the possibility of metabolic drug-drug interactions. Understanding the enzymes themselves is crucial. Over the past decade, this has occurred mostly with in vitro studies, although more recent approaches incorporate computational models to predict CYP inhibition and substrate potential. The three-dimensional displacement, or pharmacophore, of chemical features in space that are derived from inhibition data have produced pharmacophores for CYP3A4, CYP3A5 and CYP3A7, and provide new insights into ligand binding for each enzyme.

Publication types

  • Review

MeSH terms

  • Animals
  • Aryl Hydrocarbon Hydroxylases / antagonists & inhibitors
  • Aryl Hydrocarbon Hydroxylases / chemistry
  • Aryl Hydrocarbon Hydroxylases / metabolism*
  • Binding Sites
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme Inhibitors
  • Cytochrome P-450 Enzyme System / chemistry
  • Cytochrome P-450 Enzyme System / metabolism*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Kinetics
  • Ligands
  • Models, Molecular
  • Protein Binding
  • Quantitative Structure-Activity Relationship
  • Substrate Specificity

Substances

  • Cytochrome P-450 Enzyme Inhibitors
  • Enzyme Inhibitors
  • Ligands
  • Cytochrome P-450 Enzyme System
  • Aryl Hydrocarbon Hydroxylases
  • CYP3A protein, human
  • CYP3A5 protein, human
  • CYP3A7 protein, human
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human