GSK4716 is an ERRβ/γ agonist (IC50 = 2 μM) that can activate the receptor with similar potency as the protein ligand

GSK4716是一种选择性的ERRbeta/gamma激动剂[1]。在骨骼肌细胞中，ERRbeta短暂诱导而ERRgamma则显著诱导(并积累)，表现出依赖于分化的方式。用ERRbeta/gamma激动剂(GSK4716)处理分化后的骨骼肌细胞，显著增加了GRalpha（同种型D）的表达，涉及糖皮质激素受体（GR）、11β-羟类固醇脱氢酶1型（11beta-HSD1，该酶将无活性的皮质酮转化为皮质醇）以及刺激11β-HSD1氧化还原作用的己糖-6-磷酸脱氢酶（H6PDH）表达的mRNAs[2]。GSK4716被用于证明ERR受体活性对于调节运动期间骨骼肌中线粒体活性的贡献[3]。

Mouse myoblasts were isolated as described previously.?Human ERRγ-IRES green fluorescent protein adenovirus was generated by Welgen.?Following a 48-h differentiation period, myotubes were transduced with green fluorescent protein or ERRγ adenovirus for 48 h. The titers to achieve low and high levels of ERRγ expression were 1* 10^8 and 5*10^8 virus particles/ml, respectively.?GSK4716 was synthesized as described previously and dissolved in DMSO for cell culture experiments.?Cells treated with a corresponding volume of DMSO were used as controls[3]