EPZ-6438 is a potent, selective and orally bioavailable inhibitor of methyltransferase EZH2 with a Ki value of 2.5 nM. EPZ-6438 also shows a 35-fold selectivity versus EZH1 (IC50 392 nM) and >4,500-fold selectivity relative to 14 other histone methyltransferases (HMTs). [1] Oral dosing of EPZ-6438 leads to potent antitumor activity in a SMARCB1-deleted malignant rhabdoid tumor (MRT) xenograft model. [1]
EPZ-6438 is being studied in Phase III clinical trials in patients with diffuse large B-cell lymphoma [2] and relapsed/refractory synovial sarcoma [3].