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Updated: May 11, 2026

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
10:51

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists

Published on: November 15, 2013

Structure-based discovery of antagonists of nuclear receptor LRH-1

Cindy Benod1, Jens Carlsson, Rubatharshini Uthayaruban

  • 1Department of Biochemistry and Biophysics, University of California at San Francisco, San Francisco, California 94158, USA.

The Journal of Biological Chemistry
|May 14, 2013
PubMed

Insights

Researchers discovered the first small molecule antagonists for Liver Receptor Homolog 1 (LRH-1), a key gene regulator. These compounds inhibit LRH-1 activity, impacting cancer cell proliferation and offering potential molecular probes for malignancy research.

Area of Science:

  • Molecular biology
  • Endocrinology
  • Cancer research

Background:

  • Liver receptor homolog 1 (LRH-1) is a crucial nuclear receptor regulating gene transcription.
  • LRH-1 plays vital roles in early development, liver, pancreas, and intestinal functions.
  • No synthetic LRH-1 antagonists were previously known, limiting research into its functions and therapeutic potential.

Purpose of the Study:

  • To identify the first small molecule antagonists of LRH-1.
  • To investigate the effects of these antagonists on LRH-1 transcriptional activity and target gene expression.
  • To evaluate the potential of LRH-1 antagonists in inhibiting cancer cell proliferation.

Main Methods:

  • Screening of 5.2 million compounds using molecular docking.
  • In vitro direct binding and transcriptional assays for verification.
  • Treatment of human cancer cell lines (pancreatic, colon, breast) with identified antagonists.

Main Results:

  • Identified the first small molecule antagonists of LRH-1.
  • Demonstrated inhibition of LRH-1 transcriptional activity and target genes (SHP, CCNE1, G0S2).
  • Showed LRH-1 antagonist-mediated inhibition of cancer cell proliferation in multiple cell lines.

Conclusions:

  • The identified small molecules are the first synthetic antagonists of LRH-1.
  • LRH-1 antagonists effectively inhibit cancer cell growth by targeting key genes.
  • These antagonists represent valuable molecular probes for studying LRH-1 in malignancies.
Keywords:
AntagonistHormone ReceptorsInhibitorLRH-1Ligand-binding ProteinMolecular DockingNR5A2Nuclear ReceptorsTranscription Regulation

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