AF9/ENL-DOT1L PPI-IN-1

AF9/ENL-DOT1L/AF4 PPI-IN-1 is a potent AF9/ENL and histone methyltransferase DOT1L/AF4 protein-protein interactions (PPI) inhibitor. AF9/ENL-DOT1L/AF4 PPI-IN-1 can inhibit the AF9-DOT1L (IC50 = 1.5 μM), AF9-AF4 (IC50 = 1 μM), ENL-AF4 (IC50 = 1.2 μM) interactions. AF9/ENL-DOT1L/AF4 PPI-IN-1 can suppress the expression of Mixed lineage leukemia (MLL) target genes Myc and Meis1 and selectively block the proliferation of MLL-r and several other leukemia cells. AF9/ENL-DOT1L/AF4 PPI-IN-1 exhibits significant antitumor activities in a mouse model of MLL-r leukemia without overt toxicities. AF9/ENL-DOT1L/AF4 PPI-IN-1 can be used for the study of MLL-r leukemia.