Related Experiment Video

Updated: Feb 11, 2026

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
07:41

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators

Published on: February 20, 2018

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Allosteric modulation of the farnesoid X receptor by a small molecule

Matthias Gabler1, Jan Kramer1, Jurema Schmidt1

  • 1Institute of Pharmaceutical Chemistry, Goethe-University Frankfurt, Max-von-Laue-Str. 9, D-60438, Frankfurt, Germany.

Scientific Reports
|May 3, 2018
PubMed

Insights

This study identifies imatinib as a novel allosteric modulator of the farnesoid X receptor (FXR). This discovery offers a new approach for developing gene-selective FXR modulators for metabolic diseases.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Pharmacology

Background:

  • The farnesoid X receptor (FXR) is a bile acid-activated transcription factor crucial for metabolic regulation.
  • FXR agonists show therapeutic potential for non-alcoholic steatohepatitis (NASH), diabetes, and dyslipidemia.

Purpose of the Study:

  • To characterize imatinib as a first-in-class allosteric FXR modulator.
  • To develop an optimized imatinib derivative with enhanced FXR activity.

Main Methods:

  • Reporter gene assays to assess FXR activation.
  • Analysis of FXR target gene expression in HepG2 cells.
  • Evaluation of imatinib's differential effects on specific FXR target genes.

Main Results:

  • Imatinib was identified as an allosteric FXR modulator.
  • An optimized imatinib derivative significantly enhanced agonist-induced FXR activation.
  • Differential modulation of bile salt export protein and small heterodimer partner expression was observed.

Conclusions:

  • Allosteric FXR modulation represents a novel therapeutic strategy.
  • This approach may lead to the development of gene-selective FXR modulators.
  • Imatinib and its derivatives offer a promising new class of compounds for metabolic disorders.

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