Peroxisome Proliferator-Activated Receptorδ: A Target with a Broad Therapeutic Potential for Drug Discovery

The biology of Peroxisome proliferator-activated receptor (PPAR) alpha (α) and gamma (γ) has been intensely scrutinized for the last 20 years and the clinical use of both PPAR-α (fibrates) and PPAR-γ (thiazolididiones) agonists has led to the understanding of their key role in the treatment of hypertriglyceridemia and type 2 diabetes mellitus [1, 2]. In contrast, the understanding of PPAR delta (δ) biology still lags behind. The identification of small molecule agonists for PPAR-δ has shed some light on the function of this ubiquitously expressed receptor in preclinical models and early clinical studies [3]. They have revealed the multiple benefits of PPAR-δ activation on lipid disorders, diabetes, and inflammation [3, 4]. However, synthetic PPAR-δ agonists have yet to be marketed for clinical use in humans, partly due to the burden associated with their clinical development [3].