Tazemetostat CAS# 1403254-99-8 N-[(1,2-二氢-4,6-二甲基-2-氧代-3-吡啶基)甲基]-5-[乙基(四氢-2H-吡喃-4-基)氨基]-4-甲基-4'-(4-吗啉基甲基)-[1,1'-联苯]-3-甲酰胺

Tazemetostat (EPZ-6438) is a potent, selective, orally bioavailable inhibitor of enhancer of zeste homolog 2 (EZH2), the catalytic subunit of the PRC2 complex. In preclinical biochemical assays, it inhibited wild-type and mutant EZH2 methyltransferase activity with an IC50 of ~2.5 nM, reducing trimethylation of histone H3 lysine 27 (H3K27me3). In EZH2-mutant lymphoma and INI1-deficient tumor cell lines, tazemetostat induced differentiation, cell-cycle arrest, and apoptosis. In xenograft mouse models, oral administration caused dose-dependent tumor growth inhibition and durable H3K27me3 reduction in tumor tissues. Pharmacokinetic studies showed good oral exposure and tissue penetration, supporting its development for epigenetically driven cancers.