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Ziftomenib (KO-539) is a potent, selective, and orally active Menin-MLL interaction inhibitor. It affects HOXA9/MEIS1 signaling, by binding to menin and disrupting the menin-MLL protein-protein interaction, inhibiting leukemogenesis and promoting cellular differentiation in MLL-rearranged and NPM1-mutated acute myeloid leukemia.