MilliporeSigma™ Calbiochem™ Menin-MLL Interaction Inhibitor, MI-2-2

A cell-permeable thienopyrimidine compound that competes against MLL (Mixed Lineage Leukemia) for menin binding (IC₅₀ = 46 and 520 nM, respectively, against MBM1 sequence MLL_4-15 and MLL_4-43 containing both MBM1 & MBM2) by targeting menin MLL-binding pocket with high affinity ( K _D = 22nM), effectively disrupting cellular menin and MLL-AF9 fusion interaction (by >90% at 12μM in MLL-AF9-expressing HEK293 cells). Shown to inhibit the oncogenic proliferation of four MLL translocation-harboring human leukemia cell lines (by >95% in 12 d at 6μM), but not non-MLL leukemia Kasumi-1 and HAL-01 lines (≤16% inhibition at 12μM), by downregulating MLL target genes expression via simultaneous hematopoietic differentiation induction and killing of non-differentiated population.