Fibrates, glitazones, and peroxisome proliferator-activated receptors.
Several decades ago, fibrates were approved for the treatment of dyslipidemia, whereas thiazolidinediones were screened in animal models to improve glucose homeostasis and were subsequently developed for the treatment of type 2 diabetes mellitus. Relatively recently, these drugs were found to act via peroxisome proliferator-activated receptors, nuclear receptors that control lipid metabolism and glucose homeostasis. In this historical perspective, we discuss the history of discovery of the peroxisome proliferator-activated receptors, from the clinical development of their agonists to the subsequent discovery of these receptors and their mechanisms of action, to finally evoke possibilities of targeted pharmacology for future development of selective peroxisome proliferator-activated receptor modulators.
Lalloyer
Fanny
F
University Lille Nord de France, Lille, France.
Staels
Bart
B
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D002995:Clofibric Acid / Q000266:history* / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000266:history*; D055808:Drug Discovery / Q000266:history; D050171:Dyslipidemias / Q000188:drug therapy / Q000266:history*; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D007004:Hypoglycemic Agents / Q000266:history* / Q000627:therapeutic use; D000960:Hypolipidemic Agents / Q000266:history* / Q000627:therapeutic use; D050356:Lipid Metabolism / Q000187:drug effects; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists / Q000266:history*; D045162:Thiazolidinediones / Q000266:history* / Q000627:therapeutic use; D016896:Treatment Outcome
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D047492:Peroxisome Proliferator-Activated Receptors; D045162:Thiazolidinediones; D002995:Clofibric Acid
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