EZH2 and diffuse large B-cell lymphoma: In 2012, potent, highly selective S-adenosyl-methionine-competitive small molecule inhibitors of EZH2 methyltransferase activity, GSK126 [88] and EPZ005687 [89], were developed.GSK126 and EPZ005687 can bind to wild-type and Y641 mutant EZH2, leading to decreased H3K27me3 level and upregulation of expression of the silenced gene transcription, thereby effectively inhibiting the proliferation of EZH2 mutant DLBCL both in vitro and in xenograft mice models [88, 89].