VS-5584 (SB2343) (Synonyms: SB-2343;VS5584;VS 5584;SB2343;SB 2343) |
| Katalog-Nr.GC17771 |
A selective PI3K/mTOR kinase inhibitor
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1246560-33-7
Sample solution is provided at 25 µL, 10mM.
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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.
| 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. | |
| Cas No. | 1246560-33-7 | SDF | |
| Überlieferungen | SB-2343;VS5584;VS 5584;SB2343;SB 2343 | ||
| Chemical Name | 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 | ||
| Formula | C17H22N8O | M.Wt | 354.41 |
| Löslichkeit | ≥ 17.7 mg/mL in DMSO, ≥ 4.71 mg/mL in EtOH with ultrasonic | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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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 |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
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