Related Experiment Video

Updated: Jan 11, 2026

Parallel Interrogation of β-Arrestin2 Recruitment for Ligand Screening on a GPCR-Wide Scale using PRESTO-Tango Assay
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Parallel Interrogation of β-Arrestin2 Recruitment for Ligand Screening on a GPCR-Wide Scale using PRESTO-Tango Assay

Published on: March 10, 2020

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A New Era for PPARγ: Covalent Ligands and Therapeutic Applications

Jasmine L King1, Luke Smithers1, Alice Vrielink1

  • 1School of Molecular Sciences, The University of Western Australia, Crawley, 6009 Perth, Australia.

Journal of Medicinal Chemistry
|November 11, 2025
PubMed

Insights

New covalent ligands offer targeted partial activation or repression of peroxisome proliferator-activated receptor gamma (PPARγ), a key target for metabolic and inflammatory diseases, with improved safety profiles.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Drug Discovery

Background:

  • Peroxisome proliferator-activated receptor gamma (PPARγ) is a crucial transcription factor regulating metabolism, inflammation, and cell growth.
  • Its role makes it a therapeutic target for diabetes, metabolic syndrome, autoimmune diseases, and cancer.
  • Traditional PPARγ agonists cause side effects, driving research into alternative modulation strategies.

Purpose of the Study:

  • To review the current landscape of covalent PPARγ modulators.
  • To highlight chemical and structural biology insights in developing these modulators.
  • To discuss the progression of covalent PPARγ modulators into clinical trials.

Main Methods:

  • Literature review of PPARγ covalent modulator research.
  • Analysis of chemical structures and biological activities of identified ligands.
  • Examination of structural biology data informing covalent PPARγ modulation.

Main Results:

  • Identification of numerous small covalent PPARγ ligands with diverse functionalities.
  • Demonstration of therapeutic potential for various indications beyond metabolic disorders.
  • Advancement of the first covalent PPARγ drug candidates into clinical studies.

Conclusions:

  • Covalent PPARγ modulators represent a promising therapeutic strategy with potential for improved efficacy and safety.
  • Chemical and structural insights are crucial for designing effective covalent ligands.
  • The field is rapidly evolving, with ongoing clinical development offering new therapeutic avenues.

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