雌激素相关受体α（ERRα）降解的新型小分子诱导剂的鉴定
Identification of New Small-Molecule Inducers of Estrogen-related Receptor α (ERRα) Degradation.
作者信息
Peng Lijie, Zhang Zhensheng, Lei Chong, Li Shan, Zhang Zhang, Ren Xiaomei, Chang Yu, Zhang Yan, Xu Yong, Ding Ke
机构信息
International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development, Ministry of Education (MOE) of China, Guangzhou City Key Laboratory of Precision Chemical Drug Development, School of Pharmacy, Jinan University, 601 Huangpu Avenue West, Guangzhou 510632, China.
Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 190 Kaiyuan Avenue, Guangzhou 510530, China.
出版信息
ACS Med Chem Lett. 2019 Apr 12;10(5):767-772. doi: 10.1021/acsmedchemlett.9b00025. eCollection 2019 May 9.
Abstract
A series of ()-3-(4-((2,4-bis(trifluoromethyl)benzyl)oxy)-3-methoxyphenyl)-2-cyanoacrylamide derivatives were designed and synthesized as new estrogen-related receptor α (ERRα) degraders based on the proteolysis targeting chimera (PROTAC) concept. One of the representative compounds is capable of specifically degrading ERRα protein by >80% at a relatively low concentration of 30 nM, becoming one of the most potent and selective ERRα degraders to date. Compound could be utilized as a new powerful research tool for further biological investigation of ERRα.
摘要
基于蛋白酶靶向嵌合体（PROTAC）概念，设计并合成了一系列（）-3-（4-（（2,4-双（三氟甲基）苄基）氧基）-3-甲氧基苯基）-2-氰基丙烯酰胺衍生物作为新型雌激素相关受体α（ERRα）降解剂。其中一种代表性化合物能够在30 nM的相对低浓度下特异性降解ERRα蛋白超过80%，成为迄今为止最有效和最具选择性的ERRα降解剂之一。化合物可作为一种新型强大的研究工具，用于ERRα的进一步生物学研究。
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