Related Experiment Video

Updated: Feb 4, 2026

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

Published on: January 22, 2019

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Identification of Modulators That Activate the Constitutive Androstane Receptor From the Tox21 10K Compound Library

Caitlin Lynch1, Bryan Mackowiak2, Ruili Huang1

  • 1Division of Pre-Clinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland 20892.

Toxicological Sciences : an Official Journal of the Society of Toxicology
|September 25, 2018
PubMed

Insights

Researchers screened 10,000 compounds to find activators of the human constitutive androstane receptor (hCAR). Four novel activators were identified, including rimcazole, which may selectively target hCAR for drug interaction and therapy predictions.

Area of Science:

  • Pharmacology
  • Molecular Biology
  • Drug Metabolism

Background:

  • The constitutive androstane receptor (CAR; NR1I3) is a nuclear receptor crucial for drug metabolism and disposition.
  • Emerging roles for CAR in energy metabolism, tumor progression, and cancer therapy highlight the need for identifying its modulators.

Purpose of the Study:

  • To screen a large compound library for novel human CAR (hCAR) activators.
  • To characterize the identified hCAR activators for potential drug-drug interactions and therapeutic applications.

Main Methods:

  • Screening of the Tox21 10,000 compound collection to identify hCAR activators.
  • Characterization of novel structural clusters and known compound classes activating hCAR.
  • Assessment of nuclear translocation of hCAR induced by identified compounds.

Main Results:

  • A novel structural cluster of hCAR activators, including nitazoxanide and tenonitrozole, was identified.
  • Four compounds—neticonazole, diphenamid, phenothrin, and rimcazole—were characterized as novel hCAR activators.
  • Rimcazole demonstrated potential selectivity for hCAR over the pregnane X receptor (PXR).
  • All identified compounds induced hCAR translocation from the cytoplasm to the nucleus.

Conclusions:

  • The identification of novel hCAR activators provides tools for predicting drug-drug interactions.
  • These findings offer potential therapeutic agents for various diseases, including cancer.
  • Profiling hCAR activators is essential for drug development and personalized medicine.

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