PROTACERα Degrader-11 is a selective ERα PROTAC degrader with intrinsic fluorescence (Ex: 366 nm, Em: 440 nm). It demonstrates strong anti-proliferative activity, selective ERα degradation, and fluorescence imaging capability in the MCF-7 breast cancer cell line. PROTACERα Degrader-11 induces G2/M phase arrest and apoptosis in MCF-7 cells. In athymic nude mice, it shows good safety with no acute toxic reactions at a dose of 500 mg/kg. PROTACERα Degrader-11 is suitable for breast cancer research.

PROTAC ERα Degrader-11 (Compound W2) exhibits excellent cellular inhibitory activity with an IC50 of 0.19 μM against MCF-7 cells, 1.40 μM against MCF-7 EGFR cells, 4.31 μM against MCF-7 D538G cells, and 9.29 μM against MCF-7 Y537S cells after 96 hours. At a concentration of 10 μM for 0-24 hours, it degrades ERα in MCF-7 cells in a time-dependent manner; this degradation is diminished by adding ERα ligand OBHSA or CRBN ligand. At 0.5-10 μM for 24 hours, it does not degrade ERβ in PC9 cells. The fluorescence intensity of PROTAC ERα Degrader-11 (0-80 μM, 10-360 min) proportionally increases with concentration and time. It induces G2/M phase arrest and promotes apoptosis in MCF-7 cells at a concentration of 1-20 μM for 48 hours. The compound shows high photostability in the presence of ERα at 10 μM for 0-60 minutes and causes no significant damage to SD rat blood cell membranes at concentrations ranging from 0.1 to 20 μM.

PROTAC ERα Degrader-11 (Compound W2), when administered as a single intraperitoneal injection at a dose of 500 mg/kg, is well-tolerated in athymic nude mice, showing no signs of acute toxicity.