From Dual Peroxisome Proliferator Activated Receptor Agonists to Selective Peroxisome Proliferator Activated Receptor Modulators

Selcuk      Dagdelen

doi:10.2174/187221408783421273

Abstract

Worldwide epidemic of type 2 diabetes mellitus, obesity, dyslipidemia, hypertension and atherosclerosis (i.e. metabolic syndrome) still requires further treatment strategies. Life style change can be regarded as single evidenced option to manage these co-morbid conditions, at the same time. Peroxisome proliferator activated receptors (PPARs) are claimed to play critical roles in metabolic adaptation to changing environmental factors. PPAR alpha and gamma agonists are approved as hypolipidemic and antidiabetic agents, respectively. Combination of PPAR alpha and gamma agonistic effects in a single molecule (i.e. dual PPAR agonists) has been tried to achieve a better multiple cardiovascular risk management. Despite their efficacy, dual PPAR agonists has been discontinued due to safety concerns. New generation of PPAR ligands with a higher safety profile is being actively investigated. Here, we review pursuits for a new PPAR class, and discuss the potential role for selective peroxisome proliferator activated receptor modulators (SPPARMs) as new patented molecules. This article also includes recent patents on this topic.

Keywords: Peroxisome proliferator activated receptors, dual PPAR agonists, SPPARMs, type 2 diabetes, metabolic syndrome, atherosclerosis, GW0072, FK614, AMG131, nTZDpa