Estrogen receptor‐alpha (ERα) is the target of endocrine therapies for the treatment of more than 70 % of ERα‐positive breast cancers. Selective estrogen receptor degraders (SERDs) antagonize estrogen binding and target the receptor for degradation, representing the last line of treatment for resistant metastatic breast cancer patients. However, the clinical efficacy of the lone clinically approved SERD (Fulvestrant) is limited by its poor oral bioavailability. Recently, several analogues of GW5638, an acrylic acid‐based ERα ligand developed by Glaxo Research Institute in 1994, have been reported as promising orally bioavailable SERDs. Some of these compounds are currently in clinical trials, while various other structurally novel SERDs have also been reported by pharma as well as academic research groups. This review provides a critical analysis of the recent developments in orally available SERDs, with a focus on the structure–activity relationships, binding interactions and pharmacokinetic properties of these compounds

中文翻译：

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对口服生物可利用的选择性雌激素受体降解剂 (SERD) 的探索。

雌激素受体-α (ERα) 是内分泌治疗的靶标，用于治疗超过 70% 的 ERα 阳性乳腺癌。选择性雌激素受体降解剂 (SERD) 拮抗雌激素结合并靶向受体进行降解，代表了耐药转移性乳腺癌患者的最后一线治疗。然而，唯一获得临床批准的 SERD（氟维司群）的临床疗效受到其较差的口服生物利用度的限制。最近，葛兰素史克研究所于 1994 年开发的一种基于丙烯酸的 ERα 配体 GW5638 的几种类似物被报道为有前景的口服生物可利用 SERD。其中一些化合物目前正在临床试验中，而制药和学术研究小组也报告了各种其他结构新颖的 SERD。