基于二苯基庚烷骨架的新型选择性雌激素受体降解诱导剂的设计与合成。
Design and synthesis of novel selective estrogen receptor degradation inducers based on the diphenylheptane skeleton.
作者信息
Misawa Takashi, Fujisato Takuma, Kanda Yasunari, Ohoka Nobumichi, Shoda Takuji, Yorioka Momoko, Makishima Makoto, Sekino Yuko, Naito Mikihiko, Demizu Yosuke, Kurihara Masaaki
机构信息
National Institute of Health Sciences Setagaya , Tokyo , 158-8501 , Japan . Email:
Nihon University Itabashi , Tokyo , 173-8610 , Japan.
出版信息
Medchemcomm. 2016 Dec 8;8(1):239-246. doi: 10.1039/c6md00553e. eCollection 2017 Jan 1.
Abstract
Estrogen receptors (ERs) are a family of nuclear receptors (NRs) that regulate physiological effects such as reproduction and bone homeostasis. It has been reported that approximately 70% of human breast cancers are hormone-dependent and ERα-positive. Recently, novel anti-breast cancer drugs based on different mechanisms of action have received significant attention. In this article, we have designed and synthesized a selective ER degradation inducer based on the diphenylheptane skeleton. Western blotting analysis revealed that degraded ERα through the ubiquitin-proteasome system. We also performed computational docking analysis to predict the binding mode of to ERα.
摘要
雌激素受体（ERs）是一类核受体（NRs），可调节诸如生殖和骨稳态等生理效应。据报道，约70%的人类乳腺癌是激素依赖性且ERα阳性的。最近，基于不同作用机制的新型抗乳腺癌药物受到了广泛关注。在本文中，我们设计并合成了一种基于二苯基庚烷骨架的选择性ER降解诱导剂。蛋白质免疫印迹分析表明，其通过泛素-蛋白酶体系统降解ERα。我们还进行了计算机对接分析以预测其与ERα的结合模式。
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Synthesis and evaluation of tamoxifen derivatives with a long alkyl side chain as selective estrogen receptor down-regulators.具有长烷基侧链的他莫昔芬衍生物作为选择性雌激素受体下调剂的合成与评价
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Structure-activity relationships of bisphenol A analogs at estrogen receptors (ERs): discovery of an ERα-selective antagonist.双酚 A 类似物与雌激素受体（ERs）的构效关系：选择性雌激素受体拮抗剂的发现。
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Fulvestrant-induced cell death and proteasomal degradation of estrogen receptor α protein in MCF-7 cells require the CSK c-Src tyrosine kinase.氟维司群诱导 MCF-7 细胞中雌激素受体 α 蛋白的细胞死亡和蛋白酶体降解需要 CSK c-Src 酪氨酸激酶。
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