Identification of New Small-Molecule Inducers of Estrogen-related Receptor α (ERRα) Degradation
journal contributionposted on 12.04.2019, 00:00 by Lijie Peng, Zhensheng Zhang, Chong Lei, Shan Li, Zhang Zhang, Xiaomei Ren, Yu Chang, Yan Zhang, Yong Xu, Ke Ding
A series of (E)-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 6c 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 6c could be utilized as a new powerful research tool for further biological investigation of ERRα.