GW 501516

A potent and subtype-selective PPARδ agonist with Ki of 1.1 nM in human PPARδ binding assay; displays >1,000-fold selectivity over other PPAR subtypes; increases expression of the reverse cholesterol transporter ATP-binding cassette A1 and induces apolipoprotein A1-specific cholesterol efflux in macrophages, fibroblasts, and intestinal cells.Dyslipidemia Phase 2 Discontinued (In Vitro) :GW 501516 is shown to be the most potent and selective PPARδ agonists known with an EC50 of 1.1 nM against PPARδ and 1000-fold selectivity over the other human subtypes, PPARα and-γ. GW 501516 exerts anti-inflammatory effects in mouse cultured proximal tubular (mProx) cells. GW 501516 inhibits palmitate- and TNFα-induced increases in MCP-1 mRNA expression in a dose-dependent manner. (In Vivo) :GW 501516 causes impaired bone formation, leading to decreased BMD and deterioration of bone properties in OVX rats. GW 501516 attenuates interstitial inflammation and proximal tubular cell damage in a protein-overload mouse nephropathy model. GW 501516 treatment enhances running endurance and the proportion of succinate dehydrogenase (SDH) -positive muscle fibres in both trained and untrained mice.