GW 501516 (Endurobol) is a effective and highly specifc PPARβ/δ agonist (EC50: 1 nM), with 1000-fold selectivity over hPPARα/γ.

PPARδ:1 nM(Ki)

GW 501516 被显示为已知最强大且最具选择性的 PPARδ 激动剂，对 PPARα 的 EC50 为1.1 nM，并且对其他人类亚型 PPARα 和-γ 的选择性高出1000倍[1]。GW 501516 在小鼠培养的近端小管（mProx）细胞中表现出抗炎作用。GW 501516 以剂量依赖性方式抑制棕榈酸和TNFα诱导的 MCP-1 mRNA表达增加[3]。

GW 501516 在 OVX 大鼠中导致骨骼形成受损，从而降低 BMD 并恶化骨骼属性[2]。GW 501516 在蛋白过载小鼠肾病模型中减轻间质性炎症和近端肾小管细胞损伤[3]。GW 501516 治疗提高了训练和未训练小鼠的跑步耐力及琥珀酸脱氢酶（SDH）阳性肌纤维比例[4]。

Tyrosine Kinase Assays: Enzyme assays for determination of IC50 are performed in 96-well filter plates in a total volume of 0.1 mL, containing 20 mM Hepes, pH 7.4, 50 mM sodium vanadate, 40 mM magnesium chloride, 10 μM adenosine triphosphate (ATP) containing 0.5 mCi of [32P]ATP, 20 mg of polyglutamic acid/tyrosine, 10 ng of EGFR tyrosine kinase, and appropriate dilutions of CI-1033. All components except the ATP are added to the well and the plate is incubated with shaking for 10 min at 25 °C. The reaction is started by adding [32P]ATP, and the plate is incubated at 25 °C for another 10 min. The reaction is terminated by addition of 0.1 mL of 20% trichloroacetic acid (TCA). The plate is kept at 4 °C for at least 15 min to allow the substrate to precipitate. The wells are then washed five times with 0.2 mL of 10% TCA and 32P incorporation determined with a Wallac β plate counter.

GW 501516 is dissolved in DMSO. Cells are starved by incubation in 0.2% FCS DMEM for 9 h, then pre-incubated with GW 501516, at a final concentration of 2.5 and 5 μM, or 0.05% DMSO as control for 3 hours, followed by stimulation with 150 μM palmitate bound to 8.0% BSA for 12 h[3].