EED226

EED226 is a potent, selective, and orally bioavailable allosteric inhibitor of Polycomb Repressive Complex 2 (PRC2). Discovered by the Novartis Institutes for BioMedical Research (NIBR), EED226 directly binds to the H3K27me3-binding pocket of the Embryonic Ectoderm Development (EED) subunit of PRC2. This binding induces a conformational change that leads to the loss of PRC2 methyltransferase activity, effectively disrupting the interaction between EED and trimethylated lysine 27 on histone 3 (H3K27me3). Consequently, EED226 reduces global H3K27me3 levels and derepresses PRC2-target genes. In preclinical studies, EED226 has demonstrated robust antitumor activity, particularly in models of B-cell lymphoma, and has shown protective effects against cisplatin-induced acute kidney injury (AKI). EED226 served as the chemical starting point for the optimization that led to the clinical candidate MAK683.

Other names

EED-226EED226EED 226N-(furan-2-ylmethyl)-8-(4-methylsulfonylphenyl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-aminecompound 43compound43compound-43