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An inhibitor of embryonic ectoderm development protein (EED) and allosteric inhibitor of polycomb repressive complex 2 (PRC2), with 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). Disruption of the EED-EZH2 protein-protein interaction (PPI) results in a loss of H3K27me3-stimulated PRC2 activity and prevents H3K27 trimethylation. This 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. PRC2, a histone H3 lysine 27 methyltransferase and multi-protein complex comprised of EZH2, EED and suppressor of zeste 12 (SUZ12), plays a key role in gene regulation, especially during embryonic development. EZH2, the catalytic subunit of PRC2, is overexpressed or mutated in a variety of cancer cells. EED is essential for the histone methyltransferase activity of PRC2 because EED directly binds to H3K27me3. Check for \'https://www.cancer.gov/about-cancer/treatment/clinical-trials/intervention/C133819\' active clinical trials using this agent. (\'http://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI%20Thesaurus&code=C133819\' NCI Thesaurus)
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