[PPARs as molecular targets for drug discovery].

Area of Science:

• Molecular biology
• Endocrinology
• Pharmacology

Background:

• Peroxisome proliferator-activated receptors (PPARs) are crucial ligand-inducible transcription factors.
• PPARs form heterodimers with retinoid X receptors (RXRs), regulating lipid and carbohydrate metabolism.
• PPAR agonists include fibrates (PPARα) and thiazolidinediones (PPARγ), used for lipid-lowering and antidiabetic purposes.

Purpose of the Study:

• To review recent studies on ligands targeting PPAR-RXR heterodimers.
• To explore the development of novel PPAR and RXR modulators.
• To investigate the in vivo functions of newly synthesized PPAR and RXR antagonists.

Main Methods:

• Literature review of recent studies on PPAR-RXR heterodimer ligands.
• Analysis of synthesized PPAR subtype-selective agonists, dual agonists, partial agonists, antagonists, and RXR antagonists.
• Examination of in vivo functional investigations of these compounds.

Main Results:

• Development of various ligands targeting PPARs and RXRs, including agonists and antagonists.
• Investigation into the therapeutic potential of these ligands, particularly RXR antagonists, in animal models.
• Ongoing research into the in vivo functions and applications of these novel compounds.

Conclusions:

• The field has seen significant development in PPAR and RXR ligand discovery.
• PPAR and RXR modulators, including antagonists, show promise for treating metabolic disorders.
• Further in vivo investigations are crucial for understanding the therapeutic applications of these ligands.