Design and synthesis of novel selective estrogen receptor degradation inducers based on the diphenylheptane skeleton†‡,10.1039/C6MD00553E

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Lactoyl-CoA 全氟丁基戊烷白叶藤碱全氟己基辛烷新白叶藤碱壳寡糖特色专题-生物多肽

Design and synthesis of novel selective estrogen receptor degradation inducers based on the diphenylheptane skeleton†‡

Takashi Misawa,Takuma Fujisato,Yasunari Kanda,Nobumichi Ohoka,Takuji Shoda,Momoko Yorioka,Makoto Makishima,Yuko Sekino,Mikihiko Naito,Yosuke Demizu,Masaaki Kurihara

MedChemComm Pub Date : 12/08/2016 00:00:00 , DOI:10.1039/C6MD00553E

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 PBP-NC10 degraded ERα through the ubiquitin–proteasome system. We also performed computational docking analysis to predict the binding mode of PBP-NC10 to ERα.