Research Progress in Estrogen-related Receptor Gamma (ERRγ) Agonists and Inverse Agonists

Estrogen-related receptor gamma (ERR?), one of three members of the ERR family, is an inducible transcription factor. ERR? has dual functions in different tissues. The decreased expression of ERR? in the brain, stomach, prostate, and fat cells can cause neuropsychological dysfunction, gastric cancer, prostate cancer, and obesity. However, when ERR? is present in the liver, pancreas, and thyroid follicular cells, ERR? overexpression is related to liver cancer, type II diabetes, oxidative liver injury, and anaplastic thyroid carcinoma. Signaling pathway studies have confirmed that ERR? agonists or inverse agonists can regulate ERR? expression to treat related diseases. The collision between residue Phe435 and the modulator is a key factor determining the activation or inhibition of ERR?. Although more than 20 agonists and inverse agonists of ERR? have been reported, no clinical studies have been found in the literature. This review summarizes the important relationship between ERR?-related signaling pathways and diseases, research progress, and the structure-activity relationship of modulators. These findings provide guidance for further study on new ERR? modulators.