PROTAC EZH2Degrader-44 (compound 60) is a potent PROTAC degrader that targets the EZH2-PRC2 complex. It functions by recruiting the CRBN E3 ligase, relying on the proteasome system to degrade the core components EZH2, SUZ12, and EED, effectively reducing H3K27me3 and CARM1 levels. This compound exhibits antiproliferative effects through a dual mechanism: inducing mitochondrial dysfunction, which leads to decreased membrane potential, and regulating Bcl-2 family proteins (by upregulating Bax, Caspase-3, and PARP and downregulating Bcl-2), thereby significantly promoting apoptosis. PROTAC EZH2Degrader-44 demonstrates minimal cytotoxicity in human normal breast epithelial, liver, and kidney cells, providing a favorable safety profile. It is an ideal tool molecule for exploring targeted therapy mechanisms for triple-negative breast cancer.