Understanding the mechanism of cytochrome P450 3A4: recent advances and remaining problems

Dalton Trans. 2013 Mar 7;42(9):3116-26. doi: 10.1039/c2dt31833d. Epub 2012 Sep 27.


Cytochromes P450 (CYPs) represent a diverse group of heme-thiolate proteins found in almost all organisms. CYPs share a common protein fold but differ in substrate selectivity and catalyze a wide variety of monooxygenation reactions via activation of molecular oxygen. Among 57 human P450s, the 3A4 isoform (CYP3A4) is the most abundant and the most important because it metabolizes the majority of administered drugs. A remarkable feature of CYP3A4 is its extreme promiscuity in substrate specificity and cooperative substrate binding, which often leads to undesirable drug-drug interactions and toxic side effects. Owing to its importance in drug development and therapy, CYP3A4 has been the most extensively studied mammalian P450. In this review we provide an overview on recent progress and remaining problems in the CYP3A4 research.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Catalytic Domain
  • Crystallography, X-Ray
  • Cytochrome P-450 CYP3A Inhibitors
  • Cytochrome P-450 CYP3A* / chemistry
  • Cytochrome P-450 CYP3A* / metabolism
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / metabolism
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Models, Molecular


  • Cytochrome P-450 CYP3A Inhibitors
  • Enzyme Inhibitors
  • Cytochrome P-450 CYP3A