PXR, CAR and drug metabolism

Nat Rev Drug Discov. 2002 Apr;1(4):259-66. doi: 10.1038/nrd753.


Mechanisms that protect the body from a diverse array of harmful chemicals are also involved in drug metabolism, and can cause adverse drug-drug interactions. Two closely related orphan nuclear hormone receptors--the pregnane X receptor (PXR) and the constitutive androstane receptor (CAR)--have recently emerged as transcriptional regulators of cytochrome P450 expression that couple xenobiotic exposure to oxidative metabolism. In this review, we provide an examination of the roles of PXR and CAR as xenobiotic sensors, and discuss the application of this knowledge to toxicological screening in drug discovery.

Publication types

  • Review

MeSH terms

  • Animals
  • Aryl Hydrocarbon Hydroxylases*
  • Constitutive Androstane Receptor
  • Cytochrome P-450 CYP2B6
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / genetics
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Oxidoreductases, N-Demethylating / genetics
  • Pregnane X Receptor
  • Receptors, Cytoplasmic and Nuclear / chemistry
  • Receptors, Cytoplasmic and Nuclear / physiology*
  • Receptors, Steroid / chemistry
  • Receptors, Steroid / physiology*
  • Transcription Factors / chemistry
  • Transcription Factors / physiology*
  • Xenobiotics / metabolism*


  • Constitutive Androstane Receptor
  • Pregnane X Receptor
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Steroid
  • Transcription Factors
  • Xenobiotics
  • Cytochrome P-450 Enzyme System
  • Aryl Hydrocarbon Hydroxylases
  • CYP2B6 protein, human
  • Cytochrome P-450 CYP2B6
  • Cytochrome P-450 CYP3A
  • Oxidoreductases, N-Demethylating