Background:

GW501516 is subtype-selective small-molecule agonist of peroxisome proliferator-activated receptor δ (PPARδ) with Ki value of 1.1nM [1].

GW501516 is discovered by combinatorial chemistry and structure-based drug design to use as an ideal chemical tool to study the function of the ubiquitously expressed PPARδ. In the cell-based transfection assay, it induces expression of a GAL4-responsive reporter gene with EC50 value of 1.2nM. GW501516 shows more than 1000-fold selective for PPARδ over other subtypes. PPARδ is expressed in many tissues that contribute to cholesterol flux, and is a RXR of partner. As an agonist of PPARδ, GW501516 is found to increase the expression of ABCA1 as well as the apoA1-specific cholesterol efflux. In primate model of human metabolic disease, GW501516 increases the level of HDLc and lowers the fasting triglycerides. GW501516 also produces fewer, yet larger, LDL and VLDL particles results in a less atherogenic lipid composition. Furthermore, GW501516 partially corrects the hyperinsulinemia in primates without adverse effects on glycemic control [1, 2].

参考文献:
[1] Wei ZL, Kozikowski AP. A short and efficient synthesis of the pharmacological research tool GW501516 for the peroxisome proliferator-activated receptor delta. J Org Chem. 2003 Nov 14;68(23):9116-8.
[2] Oliver WR Jr, Shenk JL, Snaith MR, Russell CS, Plunket KD, Bodkin NL, Lewis MC, Winegar DA, Sznaidman ML, Lambert MH, Xu HE, Sternbach DD, Kliewer SA, Hansen BC, Willson TM. A selective peroxisome proliferator-activated receptor delta agonist promotes reverse cholesterol transport. Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5306-11.