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Current Topics in Medicinal Chemistry

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ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

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Review Article

Advances in Medicinal Chemistry of Estrogen-related Receptor Alpha (ERRα) Inverse Agonists

Author(s): Haibin Zhang, Yongli Du*, Yong Zheng, Huiting Lv, Zhijia Yan, Ning Dong, Yaling Zhu and Jingkang Shen

Volume 23, Issue 20, 2023

Published on: 22 May, 2023

Page: [1952 - 1963] Pages: 12

DOI: 10.2174/1568026623666230515145822

Price: $65

Abstract

Estrogen-related receptor alpha (ERRα), a member of the nuclear receptor superfamily, is strongly expressed in breast cancer cells. Its overexpression is associated with poor prognosis in triple- negative Breast Cancer (TNBC). ERRα expression could be inhibited by the downregulation of upstream oncogenic growth factors mTOR, HER2, and PI3K. Low expression of ERRα could suppress the migration and angiogenesis of tumor cells by inhibiting the activity of its downstream signals VEGF and WNT11. Studies have confirmed that ERRα inverse agonists can inhibit ERRα expression to treat breast cancer. Inverse agonists of ERRα could disrupt the interactions of ERRα with its coactivators and inhibit tumor development. Existing ERRα inverse agonists have shown moderate efficacy in inhibiting the growth of breast cancer cells. Clinical inverse agonists of ERRα have not been found in the literature. This review focuses on the research progress and the structureactivity relationship of ERRα inverse agonists, providing guidance for the research and discovery of new anti-tumor compounds for TNBC.

Keywords: ERRalpha, ERRalpha inverse agonists, Breast cancer, TNBC, Signaling pathways, Inverse agonistic activity.

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