MI-136

MI-136 is a small molecule inhibitor belonging to the thienopyrimidine class, designed to disrupt the protein-protein interaction between menin and Mixed Lineage Leukemia (MLL) fusion proteins. Developed at the University of Michigan, MI-136 acts by binding to menin and blocking its interaction with the N-terminal region of MLL, which is a critical oncogenic cofactor in MLL-rearranged leukemias. This disruption leads to the downregulation of leukemogenic genes such as HOXA9 and MEIS1, thereby inhibiting leukemic cell proliferation and promoting hematopoietic differentiation. MI-136 served as a lead compound for structure-based optimization, which eventually led to the development of more potent second-generation inhibitors like MI-538.