mak-683

Description: MAK-683 (extracted from patent US20160176882 A1, compound example 2) is a novel and potent inhibitor of embryonic ectoderm development protein (EED) and allosteric inhibitor of polycomb repressive complex 2 (PRC2) with IC50s of 59, 89, 26 nM in EED Alphascreen binding, LC-MS and ELISA assay. It has potential antineoplastic activity. Upon administration, MAK683 selectively binds to the domain of EED that interacts with trimethylated lysine 27 on histone 3 (H3K27me3), which leads to a conformational change in the EED H3K27me3-binding pocket and prevents the interaction of EED with the histone methyltransferase enhancer zeste homolog 2 (EZH2).

References:

1. Chan, Ho Man, et al. TRIAZOLOPYRIMIDINE COMPOUNDS AND USES THEREOF. US20160176882 A1.

2. Huang D, et al. Binding Modes of Small-Molecule Inhibitors to the EED Pocket of PRC2. Chemphyschem. 2020 Feb 4; 21(3):263-271.