EPZ005687

EPZ005687 is a potent and selective small molecule inhibitor of the Polycomb Repressive Complex 2 (PRC2) subunit **EZH2** (Enhancer of Zeste Homolog 2). It acts as a S-adenosylmethionine (SAM) competitive inhibitor, preventing the trimethylation of histone H3 at lysine 27 (H3K27me3), a key epigenetic mark associated with gene silencing. Developed by Epizyme, EPZ005687 is highly selective for EZH2 over other histone methyltransferases and is effective against both wild-type and common lymphoma-associated mutant forms of the enzyme (such as Y641 and A677). While primarily utilized as a high-quality chemical probe in preclinical research, it has demonstrated the ability to inhibit the proliferation of EZH2-mutant lymphoma cells and modulate the tumor microenvironment, including enhancing the tumoricidal activity of macrophages in mesothelioma models.