Definition

An orally bioavailable, small molecule, allosteric inhibitor of the polycomb repressive complex 2 (PRC2) component embryonic ectoderm development (EED) protein, with potential antineoplastic activity. Upon oral administration, EED inhibitor APG-5918 targets and binds to EED. This inhibits the binding of EED with trimethylated histone H3 on lysine 27 (H3K27me3), prevents the interaction of EED with the histone methyltransferase (HMT) and the catalytic subunit of the PRC2 enhancer zeste homolog 2 (EZH2), and prevents H3K27 methylation. The decrease in histone methylation alters gene expression patterns associated with cancer pathways and results in decreased tumor cell proliferation in EZH2-mutated and PRC2-dependent cancer cells. EZH2 is overexpressed or mutated in a variety of cancer cells. EED is essential for the histone methyltransferase activity of PRC2.