EZH2-IN-1 (compound 3) is a selective and SAM-competitive EZH2 and EZH1 inhibitor with an IC 50 s of 32 nM, 197 nM and 213 nM for EZH2wt, EZH2 Y641N mutant and EZH1 , respectively. EZH2-IN-1 reduces bulk H3K27me3 and H3K27me2 levels. EZH2-IN-1 has the potential for diffuse large B cell lymphoma research.