BVT 948

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.