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

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.

• Authors: Takashi Misawa, Takuma Fujisato, Yasunari Kanda, Nobumichi Ohoka, Takuji Shoda, Momoko Yorioka, Makoto Makishima, Yuko Sekino, Mikihiko Naito, Yosuke Demizu, Masaaki Kurihara
• Journal: MedChemComm (Medchemcomm) Vol. 8 Issue 1 Pg. 239-246 (Jan 01 2017) ISSN: 2040-2503 [Print] England
• PMID: 30108709 (Publication Type: Journal Article)