Necrostatin-1
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
Necrostatin-1（NEC-1，Nec-1a）[(R)-5-([7-chloro-1H-indol-3-yl]methyl)-3-methylimidazoli-dine-2,4-dione]是RIP1的抑制剂，IC50值为0.32 mM [1]。
程序性坏死是凋亡刺激诱导的坏死性细胞死亡的细胞内机制，凋亡刺激是当细胞凋亡的执行被阻止时，死亡域受体与其各自的配体结合而形成的。Necrostatin-1是程序性坏死的小分子抑制剂，也是死亡域受体相关适配器激酶RIP1的选择性变构抑制剂。
体外实验：necrostatin-1是一种选择性的死亡域受体相关适配器激酶RIP1变构抑制剂。RIP1是necrostatin-1抗坏死活性的主要靶标。此外，两个其它的necrostatins，necrostatin-3和necrostatin-5也靶向程序性坏死途径中的RIP1激酶，但通过与necrostatin-1不同的机制起作用。这些研究表明，necrostatins是RIP1激酶的先入类抑制剂，而RIP1激酶是参与程序性坏死激活的关键上游激酶 [2]。
体内实验：在小鼠中研究Nec-1对刀豆素A诱发肝炎的保护作用和机制。结果发现，Nec-1治疗小鼠中，肝功能和组织病理学变化得到改善，且炎性细胞因子的产生被抑制。Western印迹分析表明，在Nec-1治疗小鼠中，TNF-α、IFN-γ、IL2、IL6和RIP1的表达显著减少，并进一步通过免疫荧光和免疫组化进行证实。此外，Nec-1也显著减少自噬体的形成。这些研究表明，Nec-1通过RIP1相关的和自噬相关的途径阻止刀豆素A诱导的肝损伤 [3]。
临床试验：目前为止，necrostatin-1仍处于临床前开发阶段。
参考文献：
[1] Xie T, Peng W, Liu Y, Yan C, Maki J, Degterev A, Yuan J, Shi Y. Structural basis of RIP1 inhibition by necrostatins. Structure. 2013;21(3):493-9.
[2] Degterev A, Hitomi J, Germscheid M, Ch'en IL, Korkina O, Teng X, Abbott D, Cuny GD, Yuan C, Wagner G, Hedrick SM, Gerber SA, Lugovskoy A, Yuan J. Identification of RIP1 kinase as a specific cellular target of necrostatins. Nat Chem Biol. 2008;4(5):313-21.
[3] Yingqun Zhou, Weiqi Dai, Chunlei Lin, Fan Wang, Lei He, Miao Shen, Ping Chen, Chenfen Wang, Jie Lu, Ling Xu, Xuanfu Xu, and Chuanyong Guo. Protective Effects of Necrostatin-1 against Concanavalin A-Induced Acute Hepatic Injury in Mice. Mediators of Inflammation.
- 1. Cathrin Hagenlocher, Robin Siebert, et al. "ER stress-induced cell death proceeds independently of the TRAIL-R2 signaling axis in pancreatic β cells." Cell Death Discov. 2022 Jan 24;8(1):34. PMID: 35075141
- 2. Ramon Edwin Caballero, Simon Xin Min Dong, et al. "Role of RIPK1 in SMAC mimetics-induced apoptosis in primary human HIV-infected macrophages." Sci Rep. 2021 Nov 25;11(1):22901. PMID: 34824340
- 3. Xinxin Ren, Xiang Wang, et al. "Significance of TEAD Family in Diagnosis, Prognosis and Immune Response for Ovarian Serous Carcinoma." Int J Gen Med. 2021 Oct 27;14:7133-7143. PMID: 34737608
- 4. Binghua Liu, Weiyan Wang, et al. "Sodium iodate induces ferroptosis in human retinal pigment epithelium ARPE-19 cells." Cell Death Dis. 2021 Mar 3;12(3):230. PMID: 33658488
- 5. Yue Yang, yuanyuan Lu, et al. "Identification of A New Kind of Phenazine Compounds Attenuating The Stemness of Breast Cancer Cells Through Triggering Ferroptosis." Research Square. March 1st, 2021.
- 6. Zhuo Sun, Yidan Cao, et al. "Antiangiogenic effect of arsenic trioxide in HUVECs by FoxO3a‐regulated autophagy." J Biochem Mol Toxicol. 2021 Feb 16;e22728. PMID: 33592126
- 7. Zhijun Liu, Himani Nailwal, et al. "A class of viral inducer of degradation of the necroptosis adaptor RIPK3 regulates virus-induced inflammation." Immunity. 2021 Feb 9;54(2):247-258.e7. PMID: 33444549
- 8. Kai J, Yang X, et al. "Oroxylin a promotes PGC-1α/Mfn2 signaling to attenuate hepatocyte pyroptosis via blocking mitochondrial ROS in alcoholic liver disease." Free Radic Biol Med. 2020;153:89-102. PMID: 32289481
- 9. Zhang S, Yu X, et al. "Coxsackievirus A6 Induces Necroptosis for Viral Production." Front Microbiol. 2020;11:42. PMID: 32117097
- 10. Mikhail Chesnokov, Imran Khan, et al. "The MEK1/2 pathway as a therapeutic target in high-grade serous ovarian carcinoma." bioRxiv. 2019 September 16.
- 11. Wang Z, Chen J, et al. "cGAS/STING axis mediates a topoisomerase II inhibitor-induced tumor immunogenicity." J Clin Invest. 2019 Aug 13;130:4850-4862. PMID: 31408442
- 12. Qin W, Wu X, et al. "Suhuang antitussive capsule inhibits NLRP3 inflammasome activation and ameliorates pulmonary dysfunction via suppression of endoplasmic reticulum stress in cough variant asthma." Biomed Pharmacother. 2019 Jul 14;118:109188. PMID: 31315072
- 13. Ashok Kumar, Ramon Edwin Caballero, et al. "Inhibitor of apoptosis, IAP, genes play a critical role in the survival of HIV-infected macrophages." BioRxiv. 2019 February 06.
- 14. Luo Q, Yang D, et al. "Role of the Death Receptor and Endoplasmic Reticulum Stress Signaling Pathways in Polyphyllin I-Regulated Apoptosis of Human Hepatocellular Carcinoma HepG2 Cells." Biomed Res Int. 2018 Dec 25;2018:5241941. PMID: 30671458
- 15. Yuan Z, Zhang H, et al. "A new perspective of triptolide-associated hepatotoxicity: Liver hypersensitivity upon LPS stimulation." Toxicology. 2019 Feb 15;414:45-56. PMID: 30633930
- 16. Wang J, He H, et al. "Uncoupling effect of F16 is responsible for its mitochondrial toxicity and anti-cancer activity." Toxicol Sci. 2017 Oct 23. PMID: 29069523
- 17. Chirieleison SM, Marsh RA, et al. "Nucleotide-binding oligomerization domain (NOD) signaling defects and cell death susceptibility cannot be uncoupled in X-linked inhibitor of apoptosis (XIAP)-driven inflammatory disease." J Biol Chem. 2017 Apr 12. pii: jbc.M117.781500. PMID: 28404814
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 259.33 |
| Cas No. | 4311-88-0 |
| Formula | C13H13N3OS |
| Synonyms | MTH-DL-Tryptophan,Nec-1 |
| Solubility | insoluble in H2O; ≥12.97 mg/mL in DMSO; ≥13.29 mg/mL in EtOH with ultrasonic |
| Chemical Name | 5-(1H-indol-3-ylmethyl)-3-methyl-2-sulfanylideneimidazolidin-4-one |
| SDF | Download SDF |
| Canonical SMILES | CN1C(=O)C(NC1=S)CC2=CNC3=CC=CC=C32 |
| 运输条件 | 蓝冰运输或根据您的需求运输。 |
| 一般建议 | 不同厂家不同批次产品溶解度各有差异，仅做参考。若实验所需浓度过大至产品溶解极限，请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存，请尽快用完。 |
| 激酶实验 [1]: | |
|
RIP1激酶检测 |
pcDNA3-FLAG-RIP1质粒转染293T细胞，RIP1激酶实验反应条件：10 μM预冷ATP、1 μCi [γ-32P]ATP在30°C进行30分钟。使用SDS-PAGE样品缓冲溶液煮沸样品终止反应，样品进行SDS-PAGE电泳，通过放射自显影可观察到RIP1带。 |
| 细胞实验 [2]: | |
|
细胞系 |
小鼠骨细胞系（MLO-Y4） |
|
溶解方法 |
该化合物在DMSO中的溶解度 >10 mM。若配制更高浓度的溶液，一般步骤如下：请将试管置于37°C加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20°C可放置数月。 |
|
反应时间 |
30 mM; 24 h |
|
应用 |
Necrostatin-1（30 mmol/L）可在体外抑制TNF-α诱导的小鼠骨细胞系（MLO-Y4）程序性坏死。 |
| 动物实验 [2, 3]: | |
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动物模型 |
大鼠卵巢切除术；8周龄鼠做假手术或对照诱导AKI处理 |
|
剂量 |
1.65 mg/kg；腹腔注射给药；每日1次，持续4周 |
|
应用 |
Necrostatin-1（1.65 mg/kg/d）显著地减少卵巢切除大鼠的RIP1、RIP3蛋白表达；同时，Necrostatin-1预防鼠渗透性肾病变的发生及对照诱导的AKI。 |
|
注意事项 |
请于室内测试所有化合物的溶解度。实际溶解度和理论值可能略有不同，这是由实验系统的误差引起的，属于正常现象。 |
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References: 1. Degterev, A., Hitomi, J., Germscheid, M., Ch'en, I. L., Korkina, O., Teng, X., Abbott, D., Cuny, G. D., Yuan, C., Wagner, G., Hedrick, S. M., Gerber, S. A., Lugovskoy, A. and Yuan, J. (2008) Identification of RIP1 kinase as a specific cellular target of necrostatins. Nat Chem Biol. 4, 313-321 2. Cui, H., Zhu, Y., Yang, Q., Zhao, W., Zhang, S., Zhou, A. and Jiang, D. (2016) Necrostatin-1 treatment inhibits osteocyte necroptosis and trabecular deterioration in ovariectomized rats. Sci Rep. 6, 33803 3. Linkermann, A., Heller, J. O., Prokai, A., Weinberg, J. M., De Zen, F., Himmerkus, N., Szabo, A. J., Brasen, J. H., Kunzendorf, U. and Krautwald, S. (2013) The RIP1-kinase inhibitor necrostatin-1 prevents osmotic nephrosis and contrast-induced AKI in mice. J Am Soc Nephrol. 24, 1545-1557 |
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| 描述 | Necrostatin-1是一种特异性的RIP1抑制剂，抑制TNF-α诱导的程序性坏死，EC50值为490 nM。 | |||||
| 靶点 | RIP1 | |||||
| IC50 | 490 nM (EC50) | |||||
质量控制和MSDS
- 批次:
化学结构
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