Identification of New Small Molecule Inducers of Estrogen-related Receptor α (ERRα) Degradation
Identification of New Small Molecule Inducers of Estrogen-related Receptor α (ERRα) Degradation
复制标题
雌激素相关受体 α (ERR α) 降解的新小分子诱导剂的鉴定
DOI：
10.1021/acsmedchemlett.9b00025
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发表时间：
2019-05-01
影响因子：
4.2
通讯作者：
Ding, Ke
中科院分区：
文献类型：
--
作者：
Peng, Lijie;Zhang, Zhensheng;Ding, Ke
基于蛋白水解靶向嵌合体（PROTAC）概念，设计合成了一系列(E)-3-(4-（（2,4-双（三氟甲基）苯氧基）-3-甲氧基苯基）-2-氰丙烯酰胺衍生物，作为新的雌激素相关受体α (ERR α)降解剂。其中具有代表性的化合物6c能够在相对较低的浓度30 nM下特异性降解ERR α蛋白，降解率达80%，成为迄今为止最有效和选择性的ERR α降解物之一。化合物6c可作为进一步研究ERR α的有力工具。
A series of (E)-3-(4-((2,4-bis(trifluoromethyl)benzypoxy)-3-methoxyphenyl)-2-cyanoacrylamide derivatives were designed and synthesized as new estrogen-related receptor alpha (ERR alpha) degraders based on the proteolysis targeting chimera (PROTAC) concept. One of the representative compounds 6c is capable of specifically degrading ERR alpha protein by >80% at a relatively low concentration of 30 nM, becoming one of the most potent and selective ERR alpha degraders to date. Compound 6c could be utilized as a new powerful research tool for further biological investigation of ERR alpha.