EPZ011989

EPZ011989 is a potent, selective, orally bioavailable small molecule inhibitor of the protein methyltransferase **Enhancer of Zeste Homolog 2 (EZH2)**, a component of the polycomb repressive complex 2 (PRC2)[5][2][3]. EPZ011989 effectively inhibits both wild-type and mutant EZH2 with an inhibition constant (Ki) below 3 nM and demonstrates >15-fold selectivity over EZH1 and >3000-fold selectivity versus other histone methyltransferases[2][3][5]. The drug leads to reduction of cellular H3K27 methylation, resulting in antitumor activity in various preclinical cancer models, including B cell lymphoma and malignant rhabdoid tumor[1][2][5]. Mechanistically, by blocking EZH2 activity, EPZ011989 prevents aberrant gene silencing associated with oncogenic transformation and tumor growth[2][5]. It was developed and supplied by Epizyme for preclinical studies[1][5]. Primary indications under investigation include **B cell lymphoma** and **malignant rhabdoid tumor**[1][5].