Abstract
Improvements in our understanding of the functions of peroxisome proliferator-activated receptor (PPAR) subtypes as master regulators of many biological functions have made it possible to develop novel PPAR ligands with characteristic subtype selectivity as biochemical tools and/or candidatedrugs for the treatment of PPAR-dependent diseases such as metabolic syndrome, which includes type II diabetes, dyslipidemia, obesity, hypertension, and inflammation. Based on the findings that the glitazone-class antidiabetic agents, and fibrate-class antidyslipidemic agents are ligands of PPARγ and PPARα respectively, much research interest has been focused on these two subtypes as therapeutic targets for the treatment of type II diabetes and dyslipidemia. In contrast, research interest in PPARδ has been limited. However, since 2001, the availability of PPARδ knockout animals and selective ligands has led to the uncovering of possible roles of PPARδ in fatty acid metabolism, insulin resistance, reverse cholesterol transport, inflammation, and so on. It has become clear that ligands able to modulate PPARδ-mediated pathways are candidates for the treatment of altered metabolic function. This review focuses on recent medicinal chemical studies to identify PPARδ-selective agonists.
Keywords: Peroxisome proliferator-activated receptor, PPAR, PPARδ, PPARδ selective agonist, metabolic syndrome, GW-501516, TIPP-204
Current Medicinal Chemistry
Title: Design, Synthesis, and Structure-Activity Relationship Study of Peroxisome Proliferator-Activated Receptor (PPAR) δ-Selective Ligands
Volume: 14 Issue: 22
Author(s): Hiroyuki Miyachi
Affiliation:
Keywords: Peroxisome proliferator-activated receptor, PPAR, PPARδ, PPARδ selective agonist, metabolic syndrome, GW-501516, TIPP-204
Abstract: Improvements in our understanding of the functions of peroxisome proliferator-activated receptor (PPAR) subtypes as master regulators of many biological functions have made it possible to develop novel PPAR ligands with characteristic subtype selectivity as biochemical tools and/or candidatedrugs for the treatment of PPAR-dependent diseases such as metabolic syndrome, which includes type II diabetes, dyslipidemia, obesity, hypertension, and inflammation. Based on the findings that the glitazone-class antidiabetic agents, and fibrate-class antidyslipidemic agents are ligands of PPARγ and PPARα respectively, much research interest has been focused on these two subtypes as therapeutic targets for the treatment of type II diabetes and dyslipidemia. In contrast, research interest in PPARδ has been limited. However, since 2001, the availability of PPARδ knockout animals and selective ligands has led to the uncovering of possible roles of PPARδ in fatty acid metabolism, insulin resistance, reverse cholesterol transport, inflammation, and so on. It has become clear that ligands able to modulate PPARδ-mediated pathways are candidates for the treatment of altered metabolic function. This review focuses on recent medicinal chemical studies to identify PPARδ-selective agonists.
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Cite this article as:
Miyachi Hiroyuki, Design, Synthesis, and Structure-Activity Relationship Study of Peroxisome Proliferator-Activated Receptor (PPAR) δ-Selective Ligands, Current Medicinal Chemistry 2007; 14 (22) . https://dx.doi.org/10.2174/092986707781745587
DOI https://dx.doi.org/10.2174/092986707781745587 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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