Ligand recognition by drug-activated nuclear receptors PXR and CAR: structural, site-directed mutagenesis and molecular modeling studies

Mini Rev Med Chem. 2006 Aug;6(8):937-47. doi: 10.2174/138955706777935008.


Pregnane X receptor (PXR, NR1I2) and constitutive androstane receptor (CAR, NR1I3) are the principal regulators of drug/xenobiotic disposition and toxicity. These nuclear receptors display considerable cross-regulation of their target genes, and species-specific, yet promiscuous activation by a large number of structurally dissimilar ligands. Activation of PXR and/or CAR will frequently result in enhanced drug metabolism, disturbances in homeostasis of endogenous substances, and increased toxicity. Thus, understanding, measurement and prediction of ligand-elicited activation of PXR and CAR receptors is of utmost importance for the drug development process. In this mini-review, we will review the recent elucidation of structural properties of PXR and CAR, the molecular determinants of their ligand and species specificities and progress made in in silico models for identification of PXR and CAR activators.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Constitutive Androstane Receptor
  • Humans
  • Ligands
  • Models, Chemical
  • Molecular Conformation
  • Mutagenesis, Site-Directed*
  • Pharmaceutical Preparations*
  • Pregnane X Receptor
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Receptors, Steroid / metabolism*
  • Transcription Factors / metabolism*
  • Xenobiotics / metabolism


  • Constitutive Androstane Receptor
  • Ligands
  • NR1I2 protein, human
  • NR1I3 protein, human
  • Pharmaceutical Preparations
  • Pregnane X Receptor
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Steroid
  • Transcription Factors
  • Xenobiotics