VTP50469
目录号 : GC61376
VTP50469是Menin-MLL蛋白-蛋白相互作用的小分子抑制剂,Ki值为104 pM. VTP50469具有强大的抗白血病活性。
Cas No.:2169916-18-9
Sample solution is provided at 25 µL, 10mM.
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VTP50469 is a small-molecule inhibitor of the Menin-MLL protein-protein interaction with a Ki of 104 pM. VTP50469 has potently anti-leukemia activity[1-4].
VTP50469 led to a profound reduction in cell proliferation in a concentrationdependent manner in MLL-r cell lines, besides, VTP50469 treatment(330 nM; 2 and 7 days) leads to rapid downregulation of MLL fusion-driven gene expression[3].
VTP50469 (30 and 60 mg/kg;p.o.;23days) had a surprisingly extended survival advantage in MLL-r Acute Leukemia patient-derived xenograft (PDX) mice[3]. Treatment with VTP50469 significantly prolongs survival of mice engrafted with NUP98-NSD1 and NUP98-JARID1A leukemias[5].
References:
[1]. Ishchenko A, Liu Z, et al.Structure-based design technology contour and its application to the design of renin inhibitors. J Chem Inf Model. 2012 Aug 27;52(8):2089-97. doi: 10.1021/ci200605k. Epub 2012 Jul 25. PMID: 22805048.
[2].Janssens DH, Meers MP, et al. Automated CUT&Tag profiling of chromatin heterogeneity in mixed-lineage leukemia. Nat Genet. 2021 Nov;53(11):1586-1596. doi: 10.1038/s41588-021-00941-9. Epub 2021 Oct 18. PMID: 34663924; PMCID: PMC8571097.
[3]. Krivtsov AV, Evans K, 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. doi: 10.1016/j.ccell.2019.11.001. PMID: 31821784; PMCID: PMC7227117.
[4]. 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.
[5]. Heikamp EB, Henrich JA, et al. The menin-MLL1 interaction is a molecular dependency in NUP98-rearranged AML. Blood. 2022 Feb 10;139(6):894-906. doi: 10.1182/blood.2021012806. PMID: 34582559; PMCID: PMC8832476.
VTP50469是Menin-MLL蛋白-蛋白相互作用的小分子抑制剂,Ki值为104 pM. VTP50469具有强大的抗白血病活性[1-4]。
VTP50469导致MLL-r细胞系中细胞增殖以浓度依赖的方式显著减少,此外,VTP50469处理(330 nM; 2 and 7 days)导致MLL融合驱动基因表达的快速下调[3]。
VTP50469(30和60 mg/kg; ;p.o.;23days)能够让MLL-r急性白血病患者来源的异种移植(PDX)小鼠中延长生存期[3]。用VTP50469治疗可显著延长移植NUP98-NSD1和NUP98-JARID1A白血病小鼠的存活时间[5]。
| Cell experiment [1]: | |
|
Cell lines |
MOLM13 cells, RS4;11 lymphoblast cells |
|
Preparation Method |
Cells are treated for 2 and 7 days with VTP50469 or DMSO followed by RNA-seq analysis. |
|
Reaction Conditions |
330 nM; 2 and 7 days |
|
Applications |
VTP50469 treatment leads to rapid downregulation of MLL fusion-driven gene expression. |
| Animal experiment [2]: | |
|
Animal models |
Female NSG mice(7-9 week-old) |
|
Preparation Method |
The mice(carrying MV4;11-FUW-Luc-mCh-Puro cells ) were randomized into four treatment groups (n=10) based on body weight. The groups included a vehicle control and three VTP50469 groups (15, 30, 60 mg/kg BID). Treatment began on day 5 and continued for 28 days. |
|
Dosage form |
15 /30 /60mg/kg;p.o.;23days |
|
Applications |
VTP50469 treatment(30 and 60 mg/kg) had a surprisingly extended survival advantage in mice. |
|
References: [1]. Krivtsov AV, Evans K, 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. doi: 10.1016/j.ccell.2019.11.001. PMID: 31821784; PMCID: PMC7227117. |
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| Cas No. | 2169916-18-9 | SDF | |
| Canonical SMILES | O=C(N(C(C)C)C(C)C)C1=CC(F)=CC=C1OC2=CN=CN=C2N3CC4(CCN(C[C@H]5CC[C@H](NS(=O)(C)=O)CC5)CC4)C3 | ||
| 分子式 | C32H47FN6O4S | 分子量 | 630.82 |
| 溶解度 | DMSO: 125 mg/mL (198.15 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.5852 mL | 7.9262 mL | 15.8524 mL |
| 5 mM | 0.317 mL | 1.5852 mL | 3.1705 mL |
| 10 mM | 0.1585 mL | 0.7926 mL | 1.5852 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet