MI-538

MI-538 is a potent, small molecule inhibitor of the protein-protein interaction between menin and Mixed Lineage Leukemia (MLL) fusion proteins. Developed by researchers at the University of Michigan, it belongs to the thienopyrimidine class of inhibitors and was optimized from the lead compound MI-136. MI-538 binds to menin with high affinity (Kd = 6.5 nM) and disrupts the recruitment of MLL fusion proteins to their target genes, such as HOXA9 and MEIS1, which are critical for leukemogenesis. In preclinical studies, MI-538 demonstrated significant cellular activity against MLL-rearranged leukemic cells and reduced tumor growth in mouse xenograft models of acute leukemia.