EJMC-1
目录号 : GC64864EJMC-1 是一种中度有效的 TNF-α 抑制剂,IC50 为 42 μM。
Cas No.:397281-20-8
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
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- Purity: >98.00%
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- SDS (Safety Data Sheet)
- Datasheet
EJMC-1 is a moderately potent TNF-α inhibitor with an IC50 value of 42 μM[1].
[1]. Deng X, et al. Design, Synthesis, and Evaluation of Dihydrobenzo[cd]indole-6-sulfonamide as TNF-α Inhibitors. Front Chem. 2018 Apr 4;6:98.
Cas No. | 397281-20-8 | SDF | Download SDF |
分子式 | C17H11ClN2O4S | 分子量 | 374.8 |
溶解度 | DMSO : 125 mg/mL (333.51 mM; ultrasonic and warming and heat to 60°C) | 储存条件 | Store at -20°C |
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1 mg | 5 mg | 10 mg | |
1 mM | 2.6681 mL | 13.3404 mL | 26.6809 mL |
5 mM | 0.5336 mL | 2.6681 mL | 5.3362 mL |
10 mM | 0.2668 mL | 1.334 mL | 2.6681 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 | |||
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% DMSO % % Tween 80 % saline | ||||||||||
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DMSO母液配制方法: mg 药物溶于 μL DMSO溶液(母液浓度 mg/mL,
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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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Design, Synthesis, and Evaluation of Dihydrobenzo[ cd]indole-6-sulfonamide as TNF-α Inhibitors
Front Chem 2018 Apr 4;6:98.PMID:29670876DOI:PMC5893771
Tumor necrosis factor-α (TNF-α) plays a pivotal role in inflammatory response. Dysregulation of TNF can lead to a variety of disastrous pathological effects, including auto-inflammatory diseases. Antibodies that directly targeting TNF-α have been proven effective in suppressing symptoms of these disorders. Compared to protein drugs, small molecule drugs are normally orally available and less expensive. Till now, peptide and small molecule TNF-α inhibitors are still in the early stage of development, and much more efforts should be made. In a previously study, we reported a TNF-α inhibitor, EJMC-1 with modest activity. Here, we optimized this compound by shape screen and rational design. In the first round, we screened commercial compound library for EJMC-1 analogs based on shape similarity. Out of the 68 compounds tested, 20 compounds showed better binding affinity than EJMC-1 in the SPR competitive binding assay. These 20 compounds were tested in cell assay and the most potent compound was 2-oxo-N-phenyl-1,2-dihydrobenzo[cd]indole-6-sulfonamide (S10) with an IC50 of 14 μM, which was 2.2-fold stronger than EJMC-1. Based on the docking analysis of S10 and EJMC-1 binding with TNF-α, in the second round, we designed S10 analogs, purchased seven of them, and synthesized seven new compounds. The best compound, 4e showed an IC50-value of 3 μM in cell assay, which was 14-fold stronger than EJMC-1. 4e was among the most potent TNF-α organic compound inhibitors reported so far. Our study demonstrated that 2-oxo-N-phenyl-1,2-dihydrobenzo[cd]indole-6-sulfonamide analogs could be developed as potent TNF-α inhibitors. 4e can be further optimized for its activity and properties. Our study provides insights into designing small molecule inhibitors directly targeting TNF-α and for protein-protein interaction inhibitor design.