VTP50469 是一种有效的，高选择性和口服活性的 Menin-MLL 相互作用抑制剂，K_i 为 104 pM。VTP50469 具有高效的抗白血病活性。

VTP50469 is a potent, highly selective and orally active Menin-MLL interaction inhibitor with a K i of 104 pM. VTP50469 has potently anti-leukemia activity.

Solid

Ki: 104 pM (Menin-MLL interaction)

VTP50469 more potently and rapidly inhibits cell proliferation in a concentration-dependent manner in MLL-r cell lines carrying (MOLM13 (IC50 of 13 nM), THP1 (IC50 of 37 nM), NOMO1 (IC50 of 30 nM), ML2 (IC50 of 16 nM), EOL1 (IC50 of 20 nM), and murine MLL-AF9 cells (IC50 of 15 nM)) and ALL (KOPN8 (IC50 of 15 nM), HB11;19 (IC50 of 36 nM), MV4;11 (IC50 of 17 nM), SEMK2 (IC50 of 27 nM), and RS4;11 (IC50 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 chromati

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. has not independently confirmed the accuracy of these methods. They are for reference only.

Room temperature in continental US; may vary elsewhere.

Powder -20°C 3 years；4°C 2 years

[1]. Krivtsov AV, et al. A Menin-MLL Inhibitor Induces Specific Chromatin Changes and Eradicates Disease in Models of MLL-Rearranged Leukemia. Cancer Cell. 2019 Dec 9;36(6):660-673.e11.
[2]. Andrei V. Krivtsov, et al. Abstract 4958: VTP50469 is a novel, orally available menin-MLL1 inhibitor effective against MLL-rearranged and NPM1-mutant leukemia. Cancer Resceach. July 2018.Volume 78, Issue 13 Supplement.

In Vitro: DMSO : 125 mg/mL (198.15 mM; Need ultrasonic)配制储备液