PPARbeta/delta ligands as modulators of the inflammatory response.
Peroxisome proliferator-activated receptors (PPARs) are steroid hormone nuclear receptors encoded by three genes: alpha, gamma and beta/delta. Small-molecule agonists of this family of receptors, mostly PPARalpha and PPARgamma agonists, possess pronounced anti-inflammatory effects; however, the use of selective PPARbeta/delta agonists in preclinical studies suggests that this subtype also possesses anti-inflammatory properties. In vivo data suggest that ligands to the beta/delta isoform have activity in a number of disease models that are partly driven by the inflammatory response. Thus, selective activation of PPARbeta/delta may represent a promising therapeutic approach for the treatment of diseases that have inflammation as a central component of their pathophysiology. An overview of preclinical data that support the ability of PPARbeta/delta agonists to modulate the inflammatory response is provided.
Kilgore
Kenneth S
KS
GlaxoSmithKline Pharmaceuticals, Oncology for Excellence in Drug Discovery, 1250 South Collegeville Road, Collegeville, PA 19426, USA. ken.s.kilgore@gsk.com
Billin
Andrew N
AN
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D050197:Atherosclerosis / Q000188:drug therapy / Q000473:pathology; D066298:In Vitro Techniques; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D008024:Ligands; D008659:Metabolic Diseases / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D009410:Nerve Degeneration / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D047494:PPAR delta / Q000819:agonists* / Q000502:physiology*; D048068:PPAR-beta / Q000819:agonists / Q000502:physiology*; D011014:Pneumonia / Q000188:drug therapy / Q000473:pathology; D020521:Stroke / Q000188:drug therapy / Q000473:pathology; D014945:Wound Healing / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D008024:Ligands; D047494:PPAR delta; D048068:PPAR-beta