Definition

An orally bioavailable allosteric inhibitor of polycomb repressive complex 2 (PRC2), with potential antineoplastic activity. Upon oral administration, PRC2 inhibitor ORIC-944 targets and binds to the regulatory embryonic ectoderm development (EED) subunit of PRC2. This prevents the methyltransferase activity of PRC2, spefifically the methylation of histone 3 at lysine27 (H3K27). This depletes H3K27 trimethylation (H3K27me3) and modulates the expression of target genes. This may inhibit tumor cell proliferation. PRC2 is dysregulated in a variety of cancer cell types and is associated with poor prognosis. It is responsible for the methylation of H3K27 leading to transcriptional silencing. EED is essential for the histone methyltransferase activity of PRC2.