The PPAR subtype family is comprised of three members (a, g and 8) that function as lipid sensors and transcriptional regulators of nutrient homeostasis. Comprehensive
ANNUAL REPORTS IN MEDICINAL CHEMISTRY, VOLUME 41 ISSN: 0065-7743 DOI 10.1016/S0065-7743(06)41006-X
© 2006 Elsevier Inc. All rights reserved reviews detailing multiple aspects of PPAR biology have recently appeared [1-4]. In a highly choreographed sequence of events, binding of an agonist to the PPAR ligand-binding domain (LBD) induces conformational changes leading to co-repressor release and co-activator recruitment and the formation of an obligate heterodimer with RXR. Following further conformational changes, this heterodimer binds to regulatory peroxisome-proliferator-response elements (PPREs), initiating chromatin remodeling and transcriptional activation of literally hundreds of genes. The PPAR receptor subfamily LBDs are remarkably flexible and capable of accommodating a diverse array of ligands. Despite this promiscuity, creative research has yielded isoform selective agents, various dual agonists and pan agonists (vide infra).
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