VS-5584 (SB2343)
(Synonyms: SB-2343;VS5584;VS 5584;SB2343;SB 2343) 目录号 : GC17771
A selective PI3K/mTOR kinase inhibitor
Cas No.:1246560-33-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Kinase experiment [1]: | |
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In vitro mTOR kinase assays |
The reaction mixture consisted of the following components in 10 μL assay buffer (50 mM Hepes pH 7.5, 10 mM MgCl2, 3 mM MnCl2, 1 mM EGTA, 2 mM DTT, 0.01%Tween-20): 0.10 μg/mL of in-house generated mTOR enzyme, 0.05 μM ULight-eIF4E-binding protein 1 (Thr37/46) peptide and 10 μM ATP. The mixture was incubated for 60 mins at room temperature. 10 μL of Detection mixture consisted of 16 mM EDTA, 0.004 mM Eu-W1024-labeled Anti-Phospho-eIF4E-binding protein 1-(Thr37/46) antibody and 1 × LANCE? Detection Buffer was then added and incubated for 60 mins. |
| Cell experiment [1]: | |
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Cell lines |
H929 cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reaction Conditions |
Up to 10 μM; 48 hrs |
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Applications |
VS-5584 showed high anti-proliferative activity in a broad spectrum of cancer cells, with H929 cells (multiple myeloma) exhibiting the highest sensitivity in our panel (IC50 = 48 nM). |
| Animal experiment [1]: | |
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Animal models |
PTENnull human prostate PC3 xenograft model |
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Dosage form |
11 or 25 mg/kg; p.o.; q.d., for 28 days |
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Applications |
In a PTENnull human prostate PC3 xenograft model, VS-5584 treatment led to significant tumor growth inhibition (TGI) of 79% and 113% for 11 and 25 mg/kg, respectively. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Hart S, Novotny-Diermayr V, Goh KC, Williams M, Tan YC, Ong LC, Cheong A, Ng BK, Amalini C, Madan B, Nagaraj H, Jayaraman R, Pasha KM, Ethirajulu K, Chng WJ, Mustafa N, Goh BC, Benes C, McDermott U, Garnett M, Dymock B, Wood JM. VS-5584, a novel and highly selective PI3K/mTOR kinase inhibitor for the treatment of cancer. Mol Cancer Ther. 2013 Feb;12(2):151-61. | |
VS-5584 (SB2343), a purine analog, is a novel small-molecule inhibitor of both mammalian target of rapamycin (mTOR) kinase and all class I phosphoinostide 3-kinase (PI3K) isoforms that ATP-competitively inhibits the activity of mTOR, PI3Kα, PI3Kβ, PI3Kγ and PI3Kδ with values of 50% inhibition concentration IC50 of 37 nmol/L, 16 nmol/L, 68 nmol/L, 25 nmol/L and 42 nmol/L respectively. VS-5585 robustly modulates the cellular PI3K/mTOR pathway, one of the most commonly activated signaling pathways in human cancer, through inhibition of phosphorylation of substrates downstream of PI3K and mTORC1/2. Moreover, VS-5584 has been found to dose-dependently inhibit PI3K/mTOR signaling in tumor tissue resulting in tumor growth inhibition in human xengograft models.
Reference
Hart S, Novotny-Diermayr V, Goh KC, Williams M, Tan YC, Ong LC, Cheong A, Ng BK, Amalini C, Madan B, Nagaraj H, Jayaraman R, Pasha KM, Ethirajulu K, Chng WJ, Mustafa N, Goh BC, Benes C, McDermott U, Garnett M, Dymock B, Wood JM. VS-5584, a novel and highly selective PI3K/mTOR kinase inhibitor for the treatment of cancer. Mol Cancer Ther. 2013 Feb;12(2):151-61. doi: 10.1158/1535-7163.MCT-12-0466. Epub 2012 Dec 27.
| Cas No. | 1246560-33-7 | SDF | |
| 别名 | SB-2343;VS5584;VS 5584;SB2343;SB 2343 | ||
| 化学名 | 5-(8-methyl-2-morpholin-4-yl-9-propan-2-ylpurin-6-yl)pyrimidin-2-amine | ||
| Canonical SMILES | CC1=NC2=C(N=C(N=C2N1C(C)C)N3CCOCC3)C4=CN=C(N=C4)N | ||
| 分子式 | C17H22N8O | 分子量 | 354.41 |
| 溶解度 | ≥ 17.7 mg/mL in DMSO, ≥ 4.71 mg/mL in EtOH with ultrasonic | 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 | 2.8216 mL | 14.108 mL | 28.2159 mL |
| 5 mM | 0.5643 mL | 2.8216 mL | 5.6432 mL |
| 10 mM | 0.2822 mL | 1.4108 mL | 2.8216 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。