PROTAC ER? Degrader-9

PROTACER? Degrader-9 (Compound 18c) is a dual-targeting PROTAC degrader designed to diminish estrogen receptor ? (ER?) and aromatase (ARO) . It demonstrates a Ki of 0.25 ?M for ER? binding and an IC50 of 4.6 ?M for ARO inhibition. This compound curbs proliferation in wild-type MCF-7 cells (IC50=0.54 ?M) and ER? mutant variants MCF-7EGFR (IC50=0.075 ?M), MCF-7D538G (IC50=0.31 ?M), and MCF-7Y537S (IC50=2.3 ?M), while also downregulating ERS1 and MYC expression. PROTACER? Degrader-9 arrests the cell cycle at the G2/M phase and induces apoptosis in MCF-7 cells, exhibiting antitumor efficacy in mouse models.