BVT 948

BVT948是非竞争性的、细胞渗透性的新型PTP抑制剂，IC50为0.09-1.7 μM[1]。

蛋白-酪氨酸磷酸酶（PTPs）参与多种细胞内信号调节。它可以促进哺乳动物的细胞迁移[2]，在MCF-7乳腺癌细胞中诱导MMP-9的表达[3]。

BVT948通过抑制MMP-9的表达，阻断乳腺癌细胞的侵袭。0.5、1或5 μM的BVT948 治疗24小时没有显著改变MCF-7细胞的活力。BVT948以剂量依赖的方式抑制TPA诱导的MMP-9上调。使用BVT948处理MCF-7细胞，阻断TPA诱导的MMP-9蛋白表达上调。 BVT948显著减少TPA诱导的MMP-9分泌。TPA诱导后，BVT948减少50％的细胞侵袭。在TPA处理的MCF-7细胞中，BVT948通过抑制IκBα降解和NF-κB的核易位，抑制NF-κB的活化。BVT948抑制TPA诱导的MMP-9的表达，MAPK途径不参与这个过程[4]。

参考文献：
1.  Liljebris, C., Baranczewski, P., Bjrkstrand, 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.