NSC 405020 is a specific membrane matrix metalloproteinase (MT1-MMP) small molecule inhibitor[1]. NSC 405020 can activate pro-MMP-2, degrade various ECM components such as collagen, fibronectin, and laminin, thereby promoting tissue remodeling and cell migration[2]. The binding of NSC 405020 to the PEX domain of MMP-14 can effectively reduce the inflammation and fibrosis of mouse lungs induced by rectal polysaccharide antigen (SR Ag)[3].
In vitro, NSC 405020 (50μM) treatment of LEC and WM852 co cultures for 96 hours resulted in a 42% decrease in the expression of full-length and active lytic Notch3 (NICD3) in WM852 cells[4].
In vivo, intratumoral injection of NSC 405020 (0.5mg/kg, 3 times/week, 2 weeks) into BALB/c-nu/nu mice xenografted with MCF7-β3/WT and MCF7-β3/ΔPEX cells significantly inhibited tumor growth and induced fibrotic ΔPEX like tumor phenotype in vivo[5].
References：
[1] Menzel, L., Zschummel, M., Crowley, T., Franke, V., Grau, M., Ulbricht, C., Hauser, A., Siffrin, V., Bajénoff, M., Acton, S. E., Akalin, A., Lenz, G., Willimsky, G., Höpken, U. E., & Rehm, A. (2021). Lymphocyte access to lymphoma is impaired by high endothelial venule regression. Cell reports, 37(4), 109878. https://doi.org/10.1016/j.celrep.2021.109878.
[2] Vieira, D., Barralet, J., Harvey, E. J., & Merle, G. (2022). Detecting the PEX Like Domain of Matrix Metalloproteinase-14 (MMP-14) with Therapeutic Conjugated CNTs. Biosensors, 12(10), 884. https://doi.org/10.3390/bios12100884.
[3] Peng, D., Li, J., Li, Y., Bai, L., Xiong, A., He, X., Li, X., Ran, Q., Zhang, L., Jiang, M., Wang, J., Leung, E. L., Yang, P., & Li, G. (2024). MMP14high macrophages orchestrate progressive pulmonary fibrosis in SR-Ag-induced hypersensitivity pneumonitis. Pharmacological research, 200, 107070. https://doi.org/10.1016/j.phrs.2024.107070.
[4] Pekkonen, P., Alve, S., Balistreri, G., Gramolelli, S., Tatti-Bugaeva, O., Paatero, I., Niiranen, O., Tuohinto, K., Perälä, N., Taiwo, A., Zinovkina, N., Repo, P., Icay, K., Ivaska, J., Saharinen, P., Hautaniemi, S., Lehti, K., & Ojala, P. M. (2018). Lymphatic endothelium stimulates melanoma metastasis and invasion via MMP14-dependent Notch3 and β1-integrin activation. eLife, 7, e32490. https://doi.org/10.7554/eLife.32490.
[5] Remacle, A. G., Golubkov, V. S., Shiryaev, S. A., Dahl, R., Stebbins, J. L., Chernov, A. V., Cheltsov, A. V., Pellecchia, M., & Strongin, A. Y. (2012). Novel MT1-MMP small-molecule inhibitors based on insights into hemopexin domain function in tumor growth. Cancer research, 72(9), 2339–2349. https://doi.org/10.1158/0008-5472.CAN-11-4149.
NSC 405020是一种特异性膜基质金属蛋白酶（MT1-MMP）小分子抑制剂[1]。NSC 405020能够激活前MMP-2（pro-MMP-2），降解多种ECM成分（如胶原、纤维连接蛋白和层粘连蛋白），从而促进组织重塑和细胞迁移[2]。NSC 405020与MMP-14的PEX结构域结合，能够有效减少直肠多孢菌抗原（SR-Ag）诱导的小鼠肺部炎症和纤维化[3]。
在体外，NSC 405020（50μM）处理LEC和WM852的共培养物96h，WM852细胞中全长和活性裂解Notch3（NICD3）的表达降低了42%[4]。
在体内，NSC 405020（0.5mg/kg, 3 times/week, 2 weeks）瘤内注射MCF7-β3/WT 和 MCF7-β3/ΔPEX 细胞异种移植的BALB/c-nu/nu小鼠，显著抑制了肿瘤生长，并在体内引起了纤维化的ΔPEX样肿瘤表型[5]。