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.