VTP50469 fumarate is a potent, highly selective and orally active Menin-MLL interaction inhibitor with a K i of 104 pM. VTP50469 fumarate has potently anti-leukemia activity In Vitro VTP50469 more potently and rapidly inhibits cell proliferation in a concentration-dependent manner in MLL-r cell lines carrying (MOLM13 (IC 50 of 13 nM), THP1 (IC 50 of 37 nM), NOMO1 (IC 50 of 30 nM), ML2 (IC 50 of 16 nM), EOL1 (IC 50 of 20 nM), and murine MLL-AF9 cells (IC 50 of 15 nM)) and ALL (KOPN8 (IC 50 of 15 nM), HB11;19 (IC 50 of 36 nM), MV4;11 (IC 50 of 17 nM), SEMK2 (IC 50 of 27 nM), and RS4;11 (IC 50 of 25 nM)) cell lines. At early timepoints MLL-r B cell ALL (B-ALL) cell lines, but not MLL-r AML cell lines, underwent apoptosis in response to VTP50469 in a dose-dependent manner. MLL-r AML cell lines underwent dose-dependent differentiation starting at 4-6 days of exposure to VTP50469. VTP50469 displaces Menin from protein complexes and inhibits chromatin occupancy of MLL at select genes. Loss of MLL binding led to changes in gene expression, differentiation, and apoptosis. MCE has not independently confirmed the accuracy of these methods. They are for reference only. In Vivo VTP50469 (15-60 mg/kg; oral administration; twice a day; for 28 days; NSG mice) treatment is highly efficacious across all dosage levels and all treatment groups have a significant survival advantage. Mice dosed at 30 and 60 mg/kg VTP50469 extends survival advantage . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Unconditioned immunodeficient (NSG) mice with MV4;11 cells Dosage: 15 mg/kg, 30 mg/kg, and 60 mg/kg Administration: Oral administration; twice a day; for 28 days Result: Was highly efficacious across all dosage levels and all treatment groups had a significant survival advantage over the control group. Form:Solid IC50& Target:Ki: 104 pM (Menin-MLL interaction)