Discovery of ERD-308 as a Highly Potent Proteolysis Targeting Chimera (PROTAC) Degrader of Estrogen Receptor (ER)

(concentration causing 50% of protein degradation) values of 0.17 and 0.43 nM in MCF-7 and T47D ER+ breast cancer cell lines, respectively, and induces >95% of ER degradation at concentrations as low as 5 nM in both cell lines. Significantly, ERD-308 induces more complete ER degradation than fulvestrant, the only approved selective ER degrader (SERD), and is more effective in inhibition of cell proliferation than fulvestrant in MCF-7 cells. Further optimization of ERD-308 may lead to a new therapy for advanced ER+ breast cancer.