Preferred Label : EED Inhibitor MAK683;
NCIt synonyms : Ectodermal Embryonic Development Inhibitor MAK683; EED Protein-protein Interaction Inhibitor MAK683; EED PPI Inhibitor MAK683;
NCIt related terms : MAK-683;
NCIt definition : 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.;
UNII : 4K446Z8N51;
CAS number : 1951408-58-4;
Molecule name : MAK 683; MAK683;
NCI Metathesaurus CUI : CL521741;
Origin ID : C133819;
UMLS CUI : C4524908;
Semantic type(s)
- concept_is_in_subset
- has_target
