Identification of New Small-Molecule Inducers of Estrogen-related Receptor α (ERRα) Degradation

Abstract

A series of (<i>E</i>)-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 <b>6c</b> 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 <b>6c</b> could be utilized as a new powerful research tool for further biological investigation of ERRα.