MAK683

MAK683 is a first-in-class and highly selective small molecule allosteric inhibitor of the embryonic ectoderm development protein (EED), a core component of the polycomb repressive complex 2 (PRC2). By binding to EED and disrupting its interaction with trimethylated lysine 27 on histone H3 (H3K27me3), MAK683 prevents PRC2 activity and reduces H3K27 trimethylation. This leads to altered gene expression patterns associated with cancer pathways and inhibits tumor cell proliferation in EZH2-mutated or PRC2-dependent cancers. Developed by Novartis for advanced malignancies including diffuse large B-cell lymphoma (DLBCL) and various solid tumors, it has demonstrated antitumor activity in preclinical models and early clinical trials[2][3][4][5][6].

Other names

EED inhibitor-1N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-(2-methylpyridin-3-yl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine