MI-3454

MI-3454 is a potent, selective, and orally bioavailable small molecule inhibitor of the menin-KMT2A (MLL) protein-protein interaction. Developed at the University of Michigan, it specifically targets the binding pocket of menin where MLL1/MLL2 (KMT2A/KMT2B) binds. By disrupting this interaction, MI-3454 reverses the leukemogenic gene expression program driven by MLL-rearrangements or NPM1 mutations, leading to differentiation and apoptosis in leukemia cells. It has demonstrated significant anti-leukemic activity in preclinical models of MLL-rearranged and NPM1-mutated acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL).