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Current Medicinal Chemistry

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Review Article

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

Author(s): Hui Qin, Yiwen Zhang, Yutao Lou, Zongfu Pan, Feifeng Song, Yujia Liu, Tong Xu, Xiaowei Zheng, Xiaoping Hu and Ping Huang*

Volume 29, Issue 22, 2022

Published on: 13 January, 2022

Page: [3922 - 3944] Pages: 23

DOI: 10.2174/0929867328666211110101018

Price: $65

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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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