UNC1999 is a potent, selectice SAM-competitive and orally bioavailable inhibitor of EZH2/EZH1 with IC50 of <10 nM/45 nM, respectively. UNC1999 is highly selective for EZH2 and EZH1 over a broad range of epigenetic and non-epigenetic targets. UNC1999 potently reduces H3K27me3 levels in cells and selectively killed diffused large B cell lymphoma cell lines harboring the EZH2(Y641N) mutant. UNC1999 prolongs survival of a well-defined murine leukemia model bearing MLL-AF9.
