Peroxisome proliferator-activated receptor agonists and antagonists: a patent review (2014-present)

Introduction: Peroxisome proliferator-activated receptors (PPARs), PPAR alpha, PPAR delta, and PPAR gamma, play an important role in the regulation of various physiological processes, specifically lipid and energy metabolism and immunity. PPAR alpha agonists (fibrates) and PPAR gamma agonists (thiazolidinediones) are used for the treatment of hypertriglyceridemia and type 2 diabetes, respectively. PPAR delta activation enhances mitochondrial and energy metabolism but PPAR delta-acting drugs are not yet available. Many synthetic ligands for PPARs have been developed to expand their therapeutic applications. Areas covered: The authors searched recent patent activity regarding PPAR ligands. Novel PPAR alpha agonists, PPAR delta agonists, PPAR gamma agonists, PPAR alpha/gamma dual agonists, and PPAR gamma antagonists have been claimed for the treatment of metabolic disease and inflammatory disease. Methods for the combination of PPAR ligands with other drugs and expanded application of PPAR agonists for bone and neurological disease have been also claimed. Expert opinion: Novel PPAR ligands and the combination of PPAR ligands with other drugs have been claimed for the treatment of mitochondrial disease, inflammatory/autoimmune disease, neurological disease, and cancer in addition to metabolic diseases including dyslipidemia and type 2 diabetes. Selective therapeutic actions of PPAR ligands should be exploited to avoid adverse effects. More basic studies are needed to elucidate the molecular mechanisms of selective actions.