39674-97-0
39674-97-0 structure
- Name: BVT 948
- Chemical Name: 3,3-dimethyl-1H-benzo[g]indole-2,4,5-trione
- CAS Number: 39674-97-0
- Molecular Formula: C14H11NO3
- Molecular Weight: 241.24200
- Catalog: Signaling Pathways Epigenetics Histone Methyltransferase
- Create Date: 2018-12-29 10:28:56
- Modify Date: 2024-01-09 23:03:43
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BVT948 is a protein tyrosine phosphatase (PTP) inhibitor which can also inhibit several cytochrome P450 (P450) isoforms and lysine methyltransferase SETD8.
| Name | 3,3-dimethyl-1H-benzo[g]indole-2,4,5-trione |
|---|---|
| Synonyms |
Tocris-2176
4-Hydroxy-3,3-dimethyl-2H-benzo[g]indole-2,5(3H)-dione BVT 948 BVT948 |
| Description | BVT948 is a protein tyrosine phosphatase (PTP) inhibitor which can also inhibit several cytochrome P450 (P450) isoforms and lysine methyltransferase SETD8. |
|---|---|
| Related Catalog | |
| Target |
PTP[1], P450[1], SETD8[2] |
| In Vitro | Results show that the effect of BVT948 (BVT.948) is to strengthen the insulin signal and has no effects on the duration of the signal. BVT948 appears to be an effective inhibitor of both protein tyrosine phosphatases (PTP activity and P450 activity)[1]. BVT948 efficiently and selectively suppresses cellular H4 lysine 20 (H4K20me1) at doses lower than 5 μM within 24 h. The cells treated with BVT948 recapitulate cell-cycle-arrest phenotypes similar to what are reported for knocking down SETD8 by RNAi[2]. Treatment of MCF-7 cells with 0.5, 1 or 5 μM of BVT948 for 24 h does not cause any significant changes in cell viability. BVT948 inhibits TPA-induced MMP-9 up-regulation in a dose-dependent manner. Treatment with BVT948 inhibits TPA-stimulated NF-κB binding activity, but not AP-1 binding activity. BVT948 does not affect the MAPK phosphorylation by TPA. Treatment with BVT948 diminishes the TPA-induced cell invasion by 50%[3]. |
| In Vivo | Results show that 3 μmol/kg BVT948 (BVT.948) significantly enhances glucose clearance from the blood stream in response to insulin compare with vehicle-treated controls[1]. |
| Kinase Assay | 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]. |
| Cell Assay | 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]. |
| Animal Admin | 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]. |
| References |
| Density | 1.39g/cm3 |
|---|---|
| Boiling Point | 400.8ºC at 760 mmHg |
| Molecular Formula | C14H11NO3 |
| Molecular Weight | 241.24200 |
| Flash Point | 196.2ºC |
| Exact Mass | 241.07400 |
| PSA | 66.73000 |
| LogP | 1.48610 |
| Index of Refraction | 1.679 |
| Storage condition | 2-8℃ |
