NSC 405020
(Synonyms: NSC-405020) 目录号 : GC14210
NSC 405020是一种特异性膜基质金属蛋白酶（MT1-MMP）小分子抑制剂。
Cas No.:7497-07-6
Sample solution is provided at 25 µL, 10mM.
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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]。
| Cell experiment [1]: | |
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Cell lines |
184B5-MT and MCF7-β3/MT cells |
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Preparation Method |
Assays were conducted in wells of a 96-well flat bottom, white wall plates. 184B5-MT and MCF7-β3/MT cells (5×104) were grown for 16 hours in MEGM-10% FBS and DMEM-10% FBS, respectively. 184B5-MT cells were replenished with fresh MEGM (0.1mL per well) and incubated for an additional 24 hours in the presence of the NSC 405020 (100μmol/L) or vehicle (1% dimethyl sulfoxide; DMSO). MCF7-β3/MT cells were replenished with fresh DMEM-10% FBS (0.1mL per well) and incubated for an additional 6 hours in the presence of the NSC 405020 (400μmol/L) or vehicle (2%DMSO). The viable cells were counted using a luminescent ATP-Lite assay (PerkinElmer). |
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Reaction Conditions |
400μmol/L; 6h |
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Applications |
NSC 405020 (400μmol/L) did not show any cytotoxicity in MCF7-β3/MT cells and it can significantly inhibit the growth and invasive capacity of tumor cells. |
| Animal experiment [2]: | |
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Animal models |
BALB/c mice |
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Preparation Method |
In pharmacological inhibition experiments, mice were allocated randomly into three treatment groups: control group, SR-Ag ( Saccharopolyspora rectivirgula antigen) group, and SR-Ag + inhibitor group. The NSC 405020 ( 20mg/kg/mice for 2 days per week for 3 weeks ) was injected intraperitoneally into the mice before SR-Ag intratracheal installation. On day 22, mice were sacrificed and lung tissues were dissected and analyzed. |
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Dosage form |
20mg/kg; 2 days per week for 3 weeks |
|
Applications |
NSC 405020 has inhibitory effects on RAW264.7 cells exposed to SR-Ag ( Saccharopolyspora rectivirgula antigen). Treatment with NSC 405020 at aconcentration of 100nM significantly decreased the protein and mRNA levels of MMP14 in macrophages exposed to SR-Ag. |
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References: [1] 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. [2] 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. |
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| Cas No. | 7497-07-6 | SDF | |
| 别名 | NSC-405020 | ||
| 化学名 | 3,4-dichloro-N-pentan-2-ylbenzamide | ||
| Canonical SMILES | CCCC(C)NC(=O)C1=CC(=C(C=C1)Cl)Cl | ||
| 分子式 | C12H15Cl2NO | 分子量 | 260.16 |
| 溶解度 | ≥ 11.4 mg/mL in DMSO, ≥ 96.4 mg/mL in EtOH | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.8438 mL | 19.2189 mL | 38.4379 mL |
| 5 mM | 0.7688 mL | 3.8438 mL | 7.6876 mL |
| 10 mM | 0.3844 mL | 1.9219 mL | 3.8438 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Quality Control & SDS
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- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
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