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Current Medicinal Chemistry

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ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

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Review Article

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

Author(s): Yong Zheng, Yongli Du*, Haibin Zhang, Huiting Lv, Zhijia Yan, Ning Dong, Qunyi Li and Tianxiao Wang

Volume 31, Issue 24, 2024

Published on: 12 July, 2023

Page: [3653 - 3667] Pages: 15

DOI: 10.2174/0929867330666230518140631

Price: $65

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Abstract

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

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