BVT 948 |
| Catalog No.GC16256 |
An inhibitor of protein tyrosine phosphatases
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 39674-97-0
Sample solution is provided at 25 µL, 10mM.
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BVT948 is a noncompetitive, cell-permeable and novel PTP inhibitor with an IC50 of 0.09-1.7 µM. [1]
Protein-tyrosine phosphatases (PTPs) are involved in the regulation of diverse intracellular signalings. It can promote cell migration in mammalian cells [2], induce MMP-9 expression in MCF-7 breast cancer cells. [3]
BVT948 blocks breast cancer cell invasion via suppression of the expression of MMP-9. Treatment of 0.5, 1 or 5 μM BVT948 for 24 h did not cause any significant changes in MCF-7 cell viability. BVT948 inhibited TPA-induced MMP-9 up-regulation in a dose-dependent manner. Treatment MCF-7 cells with BVT948 blocked the up-regulation of TPA-induced MMP-9 protein expression. BVT948 significantly diminished TPA-induced MMP-9 secretion. BVT948 diminished 50% cell invasion after the TPA-induced. BVT948 inhibits NF-κB activation by suppressing IκBα degradation and the nuclear translocation of NF-κB in TPA-treated MCF-7 cells. The MAPK pathways are not involved in the inhibition of TPA-induced MMP-9 expression by BVT948. [4]
References:
1. Liljebris, C., Baranczewski, P., Björkstrand, E., et al. Oxidation of protein tyrosine phosphatases as a pharmaceutical mechanism of action: A study using 4-hydroxy-3,3-dimethyl-2H-benzo [g]indole-2,5(3H)-dione. J Pharmacol Exp Ther 309(2) 711-719 (2004).
2. Jallal, B., Mossie, K., Vasiloudis, G., Knyazev, P., Zachwieja, J., Clairvoyant, F., Schilling, J. and Ullrich, A. (1997) The receptor-like protein-tyrosine phosphatase DEP-1 is constitutively associated with a 64-kDa protein serine/threonine kinase. J. Biol. Chem. 272, 12158-12163.
3. Wang, F. M., Liu, H. Q., Liu, S. R., Tang, S. P., Yang, L. and Feng, G. S. (2005) SHP-2 promoting migration and metastasis of MCF-7 with loss of E-cadherin, dephosphorylation of FAK and secretion of MMP-9 induced by IL-1 beta in vivo and in vitro. Breast Cancer Res. Treat. 89, 5-14.
4. Hwang BM, Chae HS, Jeong YJ et al.Protein tyrosine phosphatase controls breast cancer invasion through the expression of matrix metalloproteinase-9.BMB Rep. 2013 Nov;46(11):533-8.
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Kinase experiment: |
To determine the reversibility of the inhibition of protein tyrosine phosphatases (PTP) activity by BVT948 (BVT.948), 50 ng of PTP1B is incubated in 100 μL of assay buffer with 20 μM BVT948 for 10 min in a concentration device. The sample is then centrifuged at 14,000 rpm at 4°C for 12 min. The concentrate is subsequently washed three times with 100 μL of assay buffer followed by centrifugation. After washing, 190 μL of assay buffer is added to the sample, increasing the volume to 200 μL. Twenty microliters are used in assays measuring enzyme activity remaining using para-nitrophenyl phosphate (pNPP) as a substrate. Controls includes enzyme, which is treated with inhibitor but not washed, and enzyme, which is not treated with BVT948 but is put through the incubation and washing procedures[1]. |
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Cell experiment: |
L6 myocytes are maintained in minimum essential medium-alpha (α-MEM) supplemented with 10% fetal bovine serum and 100 IU/mL penicillin-streptomycin at 37°C in 5% CO2. Cells are seeded into 24-well plates, and the medium is replaced with α-MEM containing 2% fetal calf serum to induce differentiation into myotubes. The medium is changed every other day, and cytidine (0.24 mg/mL medium) is added to the cultures at days 7 to 9 to suspend cycling cells. The cells are used in experiments after overnight serum starvation at days 11 to 16. They are treated with or without 25 μM BVT948 (BVT.948) for 30 min followed by 5 min of insulin (25 nM) stimulation. After freezing with liquid N2, the cells are lysed with a Tris-HCl buffer, pH 7.4, containing 1% Nonidet-40, 0.25% sodium deoxycholate, 150 mM NaCl, 1 mM EDTA, 1 mM EGTA, 1 mM sodium orthovanadate, 10 mM β-glycerophosphate, 5 mM sodium pyrophosphate, and complete protease inhibitor cocktail The cell extracts are centrifuged at 14,000 g for 10 min, and the supernatants are used in the Delfia assay[1]. |
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Animal experiment: |
Male mice 12 to 14 weeks old are used in this study. They are divided into equal groups (n=9) based on blood glucose levels. At time 0, the mice are injected with vehicle (NaCl with 10% DMSO) or BVT948 (BVT.948) (0.3 and 3 μmol/kg) and 1 U/kg insulin intraperitoneally. Blood glucose is determined from tail vein sampling at 0, 30, 60, and 120 min using a glucometer[1]. |
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References: [1]. Liljebris C, et al. Oxidation of protein tyrosine phosphatases as a pharmaceutical mechanism of action: a study using 4-hydroxy-3,3-dimethyl-2H-benzo[g]indole-2,5(3H)-dione. J Pharmacol Exp Ther. 2004 May;309(2):711-9. |
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| Cas No. | 39674-97-0 | SDF | |
| Chemical Name | 3,3-dimethyl-1H-benzo[g]indole-2,4,5-trione | ||
| Canonical SMILES | CC1(C2=C(C3=CC=CC=C3C(=O)C2=O)NC1=O)C | ||
| Formula | C14H11NO3 | M.Wt | 241.25 |
| Solubility | 0.2mg/mL in ethanol, 50mg/mL in DMSO, 5mg/mL in DMF | 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 | 4.1451 mL | 20.7254 mL | 41.4508 mL |
| 5 mM | 0.829 mL | 4.1451 mL | 8.2902 mL |
| 10 mM | 0.4145 mL | 2.0725 mL | 4.1451 mL |
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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.
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Quality Control & SDS
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- Purity: >98.50%
- 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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