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The Opportunities and Challenges of Peroxisome Proliferator-Activated Receptors Ligands in Clinical Drug Discovery and Development
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The Opportunities and Challenges of Peroxisome Proliferator-Activated Receptors Ligands in Clinical Drug Discovery and Development
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Journal Article
The Opportunities and Challenges of Peroxisome Proliferator-Activated Receptors Ligands in Clinical Drug Discovery and Development
2018
Overview
Peroxisome proliferator-activated receptors (PPARs) are a well-known pharmacological target for the treatment of multiple diseases, including diabetes mellitus, dyslipidemia, cardiovascular diseases and even primary biliary cholangitis, gout, cancer, Alzheimer’s disease and ulcerative colitis. The three PPAR isoforms (α, β/δ and γ) have emerged as integrators of glucose and lipid metabolic signaling networks. Typically, PPARα is activated by fibrates, which are commonly used therapeutic agents in the treatment of dyslipidemia. The pharmacological activators of PPARγ include thiazolidinediones (TZDs), which are insulin sensitizers used in the treatment of type 2 diabetes mellitus (T2DM), despite some drawbacks. In this review, we summarize 84 types of PPAR synthetic ligands introduced to date for the treatment of metabolic and other diseases and provide a comprehensive analysis of the current applications and problems of these ligands in clinical drug discovery and development.
Publisher
MDPI AG,MDPI
Subject
/ Anti-Inflammatory Agents - therapeutic use
/ Diabetes
/ Humans
/ Hypolipidemic Agents - therapeutic use
/ Ligands
/ Metabolic Diseases - drug therapy
/ Mice
/ Peroxisome Proliferator-Activated Receptors - agonists
/ Peroxisome Proliferator-Activated Receptors - chemistry
/ Peroxisome Proliferator-Activated Receptors - metabolism
/ Protein Isoforms - chemistry
/ Protein Isoforms - metabolism
/ Rats
/ Review
