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Updated: Jan 28, 2026

Screening for Phytoestrogens using a Cell-based Estrogen Receptor β Reporter Assay
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Identification of Compounds That Inhibit Estrogen-Related Receptor Alpha Signaling Using High-Throughput Screening

Caitlin Lynch1, Jinghua Zhao2, Srilatha Sakamuru3

  • 1National Center for Advancing Translational Sciences, National Institutes of Health (NIH), Bethesda, MD 20814, USA. caitlin.lynch@nih.gov.

Molecules (Basel, Switzerland)
|March 2, 2019
PubMed
Summary

Estrogen-related receptor alpha (ERRα) is key to energy balance and implicated in cancer. High-throughput screening identified nine cancer drugs and thirteen pesticides as ERRα antagonists, revealing new biological actions.

Keywords:
ERRαbioenergetic signaling pathwayscancerendocrine disruptionmechanism of action

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Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
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Area of Science:

  • Endocrinology
  • Molecular Biology
  • Toxicology

Background:

  • Estrogen-related receptor alpha (ERRα) is a nuclear receptor crucial for energy homeostasis and metabolic regulation.
  • ERRα, often co-activated by PGC-1α, controls genes involved in oxidative respiration and metabolic signaling.
  • Overexpression of ERRα is linked to cancer progression and metabolic diseases.

Purpose of the Study:

  • To identify compounds that modulate ERRα activity using high-throughput screening.
  • To investigate potential new mechanisms of action for existing drugs and environmental chemicals.
  • To explore the role of ERRα in cancer and metabolic disorders.

Main Methods:

  • High-throughput screening of the Tox21 10K compound library in HEK293 cells with ERRα-reporter constructs.
  • Co-transfection with PGC-1α expression plasmid to study the PGC/ERR pathway.
  • Confirmation of antagonist activity using gene expression studies.

Main Results:

  • Identified nine antineoplastic agents and thirteen pesticides as potent inhibitors of ERRα activity or the PGC/ERR pathway.
  • Confirmed novel bioenergetic mechanisms of action for five antineoplastic drugs.
  • Classified nine pesticides as novel ERRα disruptors, previously uninvestigated for this activity.

Conclusions:

  • High-throughput screening is effective for discovering new biological properties of chemicals.
  • Identified compounds offer potential for therapeutic development and understanding environmental impacts.
  • Findings broaden the understanding of ERRα's role in metabolism and disease, and the mode of action for various chemicals.