Selective estrogen receptor downregulators (SERDs) are a novel class of compounds capable of reducing the ERα protein level and blocking ER activity. Therefore, SERDs are considered as a significant therapeutic approach to treat ER+ breast cancer in both early stage and more advanced drug-resistant cases. After the FDA approval of a steroidal drug, fulvestrant, as a SERD for the treatment of breast cancer in patients who have progressed on antihormonal agents, several molecules with diverse chemical structures have been rapidly developed, studied and evaluated for selective estrogen receptor downregulation activity. Here we compile the promising SERDs reported in recent years and discuss the chemical structure and pharmacological profile of the most potent compound of the considered series. Because of the availability of only a limited number of effective drugs for the treatment of breast cancer, the quest for a potent SERD with respectable activity and bioavailability is still ongoing. The goal of this article is to make available to the reader an overview of the current progress in SERDs and provide clues for the future discovery and development of novel pharmacological potent SERDs for the treatment of breast cancer.

中文翻译：

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选择性雌激素受体下调剂（SERD）治疗乳腺癌的最新进展

选择性雌激素受体下调剂 (SERD) 是一类新型化合物，能够降低 ERα 蛋白水平并阻断 ER 活性。因此，SERD 被认为是治疗早期和晚期耐药病例 ER+ 乳腺癌的重要治疗方法。在 FDA 批准类固醇药物氟维司群作为 SERD 用于治疗使用抗激素药物治疗后病情进展的乳腺癌患者后，几种具有不同化学结构的分子已被快速开发、研究和评估其选择性雌激素受体下调活性。在这里，我们汇编了近年来报道的有前景的 SERD，并讨论了所考虑的系列中最有效的化合物的化学结构和药理学特征。由于治疗乳腺癌的有效药物数量有限，因此对具有良好活性和生物利用度的有效 SERD 的探索仍在继续。本文的目的是向读者概述 SERD 的当前进展，并为未来发现和开发用于治疗乳腺癌的新型药理有效 SERD 提供线索。