PPARs as targets for metabolic and cardiovascular diseases.
Peroxisome proliferator-activated receptors (PPARs) alpha, gamma and delta (beta) are ligand-activated transcription factors of the nuclear hormone receptor superfamily which have been shown to play key roles in maintaining glucose and lipid homeostasis. The physiological effects of several marketed drugs for the treatment of dyslipidemia (fenofibrate and gemfibrozil) and diabetes (rosiglitazone and pioglitazone) have now been shown to be mediated through PPARalpha and PPARgamma respectively. Over the past few years our understanding of how PPAR ligands and receptors modulate gene expression has greatly increased; this knowledge is being used to design even more potent and efficacious PPAR ligands for the treatment of diabetes, dyslipidemia, atherosclerosis and obesity. This review is a brief survey of the PPAR field which highlights recent progress, with an emphasis on new ligands with novel PPAR profiles, particularly compounds which are co-agonists of PPAalpha, gamma and beta (delta).
Cheng
Peter T W
PT
Bristol Myers Squibb Company, 311 Pennington Rocky Hill Road, Pennington, NJ 08534, USA.
Mukherjee
Ranjan
R
D000818:Animals; D000963:Antimetabolites / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000378:metabolism; D016503:Drug Delivery Systems; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008024:Ligands; D050356:Lipid Metabolism; D008659:Metabolic Diseases / Q000188:drug therapy* / Q000378:metabolism; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014157:Transcription Factors / Q000187:drug effects* / Q000378:metabolism
D000963:Antimetabolites; D008024:Ligands; D047492:Peroxisome Proliferator-Activated Receptors; D014157:Transcription Factors; D005947:Glucose