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VTP50469
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
VTP50469图片
规格:98%
分子量:630.82
包装与价格:
包装价格(元)
5mg电议
10mg电议

产品介绍
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,Ki为104pM。VTP50469具有高效的抗白血病活性。
货号:ajcx31656
CAS:2169916-18-9
分子式:C32H47FN6O4S
分子量:630.82
溶解度:DMSO: 125 mg/mL (198.15 mM)
纯度:98%
存储:Store at -20°C
库存:现货

Background:

VTP50469 is a potent, highly selective and orally active Menin-MLL interaction inhibitor with a Ki of 104 pM. VTP50469 has potently anti-leukemia activity[1][2].

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[1].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[1]. 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[1].

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[1]. Animal Model: Unconditioned immunodeficient (NSG) mice with MV4;11 cells[1]

[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.