Misawa Takashi, Fujisato Takuma, Kanda Yasunari, Ohoka Nobumichi, Shoda Takuji, Yorioka Momoko, Makishima Makoto, Sekino Yuko, Naito Mikihiko, Demizu Yosuke, Kurihara Masaaki
National Institute of Health Sciences Setagaya , Tokyo , 158-8501 , Japan . Email:
Nihon University Itabashi , Tokyo , 173-8610 , Japan.
Medchemcomm. 2016 Dec 8;8(1):239-246. doi: 10.1039/c6md00553e. eCollection 2017 Jan 1.
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.
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。
