APG-5918

APG-5918 is an orally bioavailable, potent, and selective small-molecule inhibitor of the embryonic ectoderm development (EED) protein, a core component of the polycomb repressive complex 2 (PRC2). By allosterically binding to EED—specifically at the H3K27me3 domain—APG-5918 disrupts PRC2 function by preventing EED from interacting with the histone methyltransferase EZH2. This leads to downregulation of key epigenetic markers and cell cycle regulators, induction of apoptosis, and cell cycle arrest in tumor cells. APG-5918 has demonstrated antitumor activity in preclinical models across various cancer types including B-cell non-Hodgkin lymphoma, malignant rhabdoid tumor, mesothelioma, prostate cancer, and T-cell lymphomas. It is being developed by Ascentage Pharma for hematologic malignancies and advanced solid tumors[1][3][6][8].