Protein tyrosine phosphatases (PTPs) play a multifunctional role in coordinating signaling networks. BVT 948 is an inhibitor of PTPs with IC50 values of 0.9±0.3μM, 1.7±0.1μM, 0.09±0.01μM, 1.5±0.4μM, and 0.7±0.05μM for PTP1B, TCPTP, SHP-2, LAR, and YopH, respectively. It also exhibited robust inhibitory effects against several cytochrome P450 isoforms in vitro. BVT 948 at a concentration of 25μM stimulated glucose uptake into L6 myotubes in a PI3K-dependent fashion. Mice treated with 3μmol/kg BVT 948 showed significantly increased glucose clearance from the bloodstream in response to insulin compared with the vehicle-treated group.[1]
作用机制
BVT 948 is a noncompetitive inhibitor of PTP. It irreversibly inhibits PTP1B activity in vitro by catalyzing the catalytic cysteine residue of the enzyme.[1]
BVT948 细胞实验
Cell Line
Concentration
Treated Time
Description
References
HEK293T cells
5 μM
3 days
Inhibition of SETD8's methyltransferase activity, leading to rapid depletion of H4K20me1 mark
ACS Chem Biol. 2014 Nov 21;9(11):2471-8
MCF-7 cells
1 μM and 5 μM
24 h
To study the effect of BVT948 on TPA-induced MMP-9 expression, showing dose-dependent inhibition of TPA-induced MMP-9 mRNA and protein up-regulation.
BMB Rep. 2013 Nov;46(11):533-8
MCF-7 cells
1 μM and 5 μM
24 h
To investigate the cytotoxicity of BVT948 on MCF-7 cells, showing no significant changes in cell viability at 1 μM and 5 μM concentrations for 24 h.
BMB Rep. 2013 Nov;46(11):533-8
HepG2
19.5–100 μM/mL
24 h
To evaluate the cytotoxicity of BVT-948 and alexidine dihydrochloride. The EC50 value for BVT-948 was 39.8 μM with a selectivity index of 36.
Int J Parasitol Drugs Drug Resist. 2022 Aug;19:81-88
BVT948 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Rat
Spared nerve injury (SNI) model
Incubation in spinal cord slices
10 μM
60 min pretreatment followed by 2 min NMDA+D-Ser treatment
BVT948 enhances NMDA receptor activation by augmenting phosphorylation of Tyr1472 on the NR2B subunit, thereby promoting NPY release as evidenced by increased Y1 receptor internalization.
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