Overview of PROTACs Targeting the Estrogen Receptor: Achievements
for Biological and Drug Discovery

Hui       Qin; Yiwen       Zhang; Yutao       Lou; Zongfu       Pan; Feifeng       Song; Yujia       Liu; Tong       Xu; Xiaowei       Zheng; Xiaoping       Hu; Ping       Huang
doi:10.2174/0929867328666211110101018
Abstract

Estrogen receptors (ERs) are steroid hormone receptors, which belong to a large nuclear receptor family. Endocrine diseases correlate strongly with dysregulated ER signaling. Traditional therapies continue to rely on small molecule inhibitors, including aromatase inhibitors (AIs) and selective estrogen receptor modulators (SERMs), all of which permit acquired resistance to endocrine therapy. Proteolytic targeting chimeras (PROTACs) offer unprecedented potential for solving acquired endocrine resistance. ARV-471, an ER-targeting PROTAC developed by Arvinas, was designated as an Investigational New Drug by the US FDA in 2019, and a phase I trial in patients suffering from locally advanced or metastatic ER-positive/HER2- negative breast cancer was initiated. In this review, we will focus on progress in developing ER-targeting PROTACs from publications and patents aimed at the treatment of endocrine diseases.
Keywords: PROTACs, Estrogen receptors (ERs), nuclear receptor (NR), DNA binding region, ER-α, ER-β.
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DOI https://dx.doi.org/10.2174/0929867328666211110101018	Print ISSN 0929-8673
Publisher Name Bentham Science Publisher	Online ISSN 1875-533X
Current Medicinal Chemistry

Overview of PROTACs Targeting the Estrogen Receptor: Achievements for Biological and Drug Discovery

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