The nuclear estrogen-related receptor α (ERRα) plays a central role in the regulation of expression of the genes involved in mitochondrial biogenesis and oxidative metabolism.Several classes of ERRα inverse agonists have been identified, but agonist are rarely reported.We have successfully identified DK3 as new agonist enhancing the transcriptional functions of ERRα.DK3 potently and selectively elevated both the mRNA levels and the protein levels of ERRα.Consequently, DK3 also potently alleviate glucose intolerance in HFD model and Ob/Ob model.