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Updated: Jul 14, 2026
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Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
Published on: November 15, 2013
Evolution of peroxisome proliferator-activated receptor agonists
Feng Chang1, Linda A Jaber, Helen D Berlie
1Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201, USA.
The Annals of Pharmacotherapy
|May 24, 2007
Summary
New peroxisome proliferator-activated receptor (PPAR) agonists are being developed to treat metabolic syndrome, type 2 diabetes, and dyslipidemia. These agents aim for improved safety and efficacy by targeting multiple PPAR subtypes or acting as partial agonists.
Area of Science:
- Endocrinology and Metabolism
- Pharmacology
- Molecular Biology
Background:
- Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors crucial for regulating lipid metabolism, adipocyte function, and insulin sensitivity.
- Dysregulation of PPAR pathways is implicated in type 2 diabetes, dyslipidemia, obesity, and the metabolic syndrome.
Purpose of the Study:
- To review the evolution of PPAR agonists from single-target to multi-subtype or partial agonists.
- To discuss their application in treating type 2 diabetes, dyslipidemia, obesity, and metabolic syndrome.
Main Methods:
- Literature search of MEDLINE (1966-March 2007) using relevant PPAR agonist keywords.
- Inclusion of data from pharmaceutical companies, internet resources, and scientific meeting abstracts.
- Review and summarization of animal data, abstracts, clinical trials, and review articles.
Main Results:
- PPAR alpha, gamma, and delta receptors are key regulators of lipid and glucose metabolism.
- Dual PPAR agonists showed promise but were limited by adverse effects.
- Investigational agents include PPAR-delta agonists, partial PPAR-gamma agonists (e.g., metaglidasen), and pan agonists (e.g., netoglitazone) with improved selectivity.
- Metaglidasen demonstrated improvements in HbA1c and triglycerides with a favorable safety profile.
Conclusions:
- Modulating PPAR activity offers a therapeutic strategy for glucose, lipid, and weight management.
- While early dual agonists faced toxicity challenges, ongoing research focuses on developing safer, more selective PPAR agonists.
- Newer agents hold potential for treating multiple facets of the metabolic syndrome with improved safety and efficacy.
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