AF9/ENL-DOT1L PPI-IN-1

AF9/ENL-DOT1L/AF4 PPI-IN-1 is a potent inhibitor of protein-protein interactions (PPI) between AF9/ENL and the histone methyltransferase DOT1L/AF4. It effectively inhibits the interactions of AF9-DOT1L (IC50= 1.5 μM), AF9-AF4 (IC50= 1 μM), and ENL-AF4 (IC50= 1.2 μM) . This compound suppresses the expression of MLL target genes, Myc and Meis1, and selectively blocks the proliferation of MLL-r and other leukemia cells. In a mouse model of MLL-r leukemia, AF9/ENL-DOT1L/AF4 PPI-IN-1 demonstrates significant antitumor activity with no notable toxicity. It is a useful agent for studying MLL-r leukemia.