HY809382

HY809382 is a potent, orally bioavailable proteolysis-targeting chimera (PROTAC) designed to degrade the Polycomb repressive complex 2 (PRC2). It specifically targets the EED (Embryonic Ectoderm Development) subunit of the complex, recruiting the Cereblon (CRBN) E3 ubiquitin ligase to induce its proteasomal degradation. The loss of EED subsequently leads to the destabilization and degradation of the catalytic subunits EZH1 and EZH2, resulting in a global reduction of H3K27me3 (histone H3 lysine 27 trimethylation) levels and the reactivation of silenced tumor suppressor genes. Developed by Huayuan Biopharma, HY809382 has demonstrated significant anti-tumor activity in preclinical models of diffuse large B-cell lymphoma (DLBCL), rhabdoid tumors, and prostate cancer, showing superior efficacy compared to traditional EZH2 small-molecule inhibitors.