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

A cell-permeable thienopyrimidine compound that competes against MLL (Mixed Lineage Leukemia) for menin binding (IC50 = 46 and 520 nM, respectively, against MBM1 sequence MLL4-15 and MLL4-43 containing both MBM1 & MBM2) by targeting menin MLL-binding pocket with high affinity (KD = 22 nM by ITC), effectively disrupting cellular menin and MLL-AF9 fusion interaction (by >90% at 12 µM 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 cultures with 6 µM MI-2-2), including MV4;11 (MLL-AF4), ML-2 (MLL-AF6), MOLM-13 (MLL-AF9), and KOPN-8 (MLL-ENL), but not non-MLL leukemia Kasumi-1 and HAL-01 lines (≤16% inhibition with 12 µM MI-2-2), by downregulating MLL target genes expression (36% and 31% of DMSO control Hoxa9 and Meis1 mRNA level, respectively, in 4 d 6 µM MI-2-2-treated MV4;11), via simultaneous hematopoietic differentiation induction (5% and 41% CD11b population, respectively, in 10 d MV4;11 culture with DMSO or 6 µM MI-2-2) and killing of non-differentiated population (81% and 63% viability in 2 d MV4;11 culture with DMSO or 6 µM MI-2-2).

Glass bottle