Kevetrin hydrochloride (4-Isothioureidobutyronitrile hydrochloride)
(Synonyms: 4-Isothioureidobutyronitrile hydrochloride; thioureidobutyronitrile hydrochloride; thioureido butyronitrile hydrochloride) 目录号 : GC32919
An activator of p53
Cas No.:66592-89-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Kevetrin is an activator of p53.1,2 It increases levels of activated p53 and expression of p21 in A549 cells and decreases expression of the transcription factor E2F1 in a variety of cell lines.1,2 Kevetrin decreases cell viability in a panel of cancer cell lines with a mean IC50 value of 0.49 μM.3 It reduces tumor growth in MDA-MB-231, HT-29, PC3, HCT15, A549, NCI-H1975, CRL-1619, LNCaP, MIA PaCa, and SCC-5 mouse xenograft models when administered at a dose of 200 mg/kg.
1.Kumar, A., Hiran, T., Holden, S.A., et al.Abstract 4470: KevetrinTM, a novel small molecule, activates p53, enhances expression of p21, induces cell cycle arrest and apoptosis in a human cancer cell lineCancer Res.71(8 Supp)4470(2011) 2.Kumar, A., Holden, S.A., Chafai-Fadela, K., et al.Abstract 2874: Kevetrin targets both MDM2-p53 and Rb-E2F pathways in tumor suppressionCancer Res.72(8 Supp)2874(2012) 3.Menon, K.Nitrile derivatives and their pharmaceutical use and compositions(2012)
| Cas No. | 66592-89-0 | SDF | |
| 别名 | 4-Isothioureidobutyronitrile hydrochloride; thioureidobutyronitrile hydrochloride; thioureido butyronitrile hydrochloride | ||
| Canonical SMILES | NC(SCCCC#N)=N.[H]Cl | ||
| 分子式 | C5H10ClN3S | 分子量 | 179.67 |
| 溶解度 | DMSO : ≥ 40 mg/mL (222.63 mM) | 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 | 5.5658 mL | 27.8288 mL | 55.6576 mL |
| 5 mM | 1.1132 mL | 5.5658 mL | 11.1315 mL |
| 10 mM | 0.5566 mL | 2.7829 mL | 5.5658 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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Inhibition of mycobacteria proliferation in macrophages by low cisplatin concentration through phosphorylated p53-related apoptosis pathway
PLoS One 2023 Jan 31;18(1):e0281170.PMID:36719870DOI:PMC9888694
Background: Drug resistance is a prominent problem in the treatment of tuberculosis, so it is urgent to develop new anti- tuberculosis drugs. Here, we investigated the effects and mechanisms of cisplatin (DDP) on intracellular Mycobacterium smegmatis to tap the therapeutic potential of DDP in mycobacterial infection. Results: Macrophages infected with Mycobacterium smegmatis were treated with DDP alone or combined with isoniazid or rifampicin. The results showed that the bacterial count in macrophages decreased significantly after DDP (≤ 6 μg/mL) treatment. When isoniazid or rifampicin was combined with DDP, the number of intracellular mycobacteria was also significantly lower than that of isoniazid or rifampicin alone. Apoptosis of infected cells increased after 24 h of DDP treatment, as shown by flow cytometry and transmission electron microscopy detection. Transcriptome sequencing showed that there were 1161 upregulated and 645 downregulated differentially expressed genes (DEGs) between the control group and DDP treatment group. A Trp53-centered protein interaction network was found based on the top 100 significant DEGs through STRING and Cytoscape software. The expression of phosphorylated p53, Bax, JAK, p38 MAPK and PI3K increased after DDP treatment, as shown by Western blot analysis. Inhibitors of JAK, PI3K or p38 MAPK inhibited the increase in cell apoptosis and the reduction in the intracellular bacterial count induced by DDP. The p53 promoter Kevetrin hydrochloride scavenges intracellular mycobacteria. If combined with DDP, Kevetrin hydrochloride could increase the effect of DDP on the elimination of intracellular mycobacteria. In conclusion, DDP at low concentrations could activate the JAK, p38 MAPK and PI3K pathways in infected macrophages, promote the phosphorylation of p53 protein, and increase the ratio of Bax to Bcl-2, leading to cell apoptosis, thus eliminating intracellular bacteria and reducing the spread of mycobacteria. Conclusion: DDP may be a new host-directed therapy for tuberculosis treatment, as well as the p53 promoter Kevetrin hydrochloride.