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Updated: Sep 29, 2025

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
Published on: November 15, 2013
A concise review on hPXR ligand-recognizing residues and structure-based strategies to alleviate hPXR transactivation
Tao Liu1, James P Beck1, Junliang Hao1
1Discovery Chemistry Research & Technologies, Eli Lilly and Company, Lilly Biotechnology Center 10290 Campus Point Drive San Diego CA 92121 USA liu_tao2@lilly.com.
Abstract:
The human pregnane X receptor (hPXR) regulates the expression of major drug metabolizing enzymes. A wide range of drug candidates bind and activate hPXR, and hence are at risk of increasing drug-drug interactions and reducing clinical efficacy. hPXR structural features that function as hot spots for ligand binding are identified and highlighted in this concise review. Based on literature structure-activity relationship data as case studies, structure-based strategies to mitigate hPXR transactivation are summarized for medicinal chemists.
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