GW501516

GW501516 (GSK-516, GW1516) is a potent and highly selective PPARbeta/delta agonist, with EC50 of 1 nM, with 1000-fold selectivity over hPPARalpha and hPPARgamma. The PPARbeta/delta agonist GW501516 inhibited the increase caused by TNF-alpha in the mRNA levels of the NF-kappaB target genes interleukin 8 (IL-8), TNF-alpha and thymic stromal lymphopoietin (TSLP). GW501516 exhibited agonist effects with EC(50) values of 560 and 55 nM against PPARalpha and PPARdelta, respectively, in a luciferase assay. Moreover, GW501516 also exhibited potent ability to induce oleic acid oxidation in a human myotube cell assay with EC(50)=3.7 nM. In contrast, GW501516 treatment decreased TNF-alpha-induced p65 acetylation. GW501516 increased AMPK phosphorylation and the subsequent p300 phosphorylation, leading to a marked reduction in the association between p65 and this transcriptional co-activator.

GSK-516, GW1516

C21H18F3NO3S2

0, 9983