Elucidating the 'Jekyll and Hyde' nature of PXR: The case for discovering antagonists or allosteric antagonists

Arunima Biswas, Sridhar Mani, Matthew R. Redinbo, Matthew D. Krasowski, Hao Li, Sean Ekins

Research output: Contribution to journalReview articlepeer-review

52 Scopus citations


The pregnane X receptor belongs to the nuclear hormone receptor superfamily and is involved in the transcriptional control of numerous genes. It was originally thought that it was a xenobiotic sensor controlling detoxification pathways. Recent studies have shown an increasingly important role in inflammation and cancer, supporting its function in abrogating tissue damage. PXR orthologs and PXR-like pathways have been identified in several non-mammalian species which corroborate a conserved role for PXR in cellular detoxification. In summary, PXR has a multiplicity of roles in vivo and is being revealed as behaving like a "Jekyll and Hyde" nuclear hormone receptor. The importance of this review is to elucidate the need for discovery of antagonists of PXR to further probe its biology and therapeutic applications. Although several PXR agonists are already reported, virtually nothing is known about PXR antagonists. Here, we propose the development of PXR antagonists through chemical, genetic and molecular modeling approaches. Based on this review it will be clear that antagonists of PXR and PXR-like pathways will have widespread utility in PXR biology and therapeutics.

Original languageEnglish (US)
Pages (from-to)1807-1815
Number of pages9
JournalPharmaceutical Research
Issue number8
StatePublished - Aug 2009


  • Agonists
  • Antagonists
  • Machine learning
  • Pharmacophore
  • Pregnane X receptor

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)


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