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Necrostatin-1

Necrostatin-1

产品编号 T1847   CAS 4311-88-0
别名: Nec-1, Necrostatin 1

Necrostatin-1 (Nec-1) 是一种坏死性凋亡抑制剂和 RIP1 抑制剂,具有特异性。Necrostatin-1 抑制 TNF-α 诱导的坏死性凋亡。Necrostatin-1 也可以抑制 IDO

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Necrostatin-1 Chemical Structure
Necrostatin-1, CAS 4311-88-0
规格 价格/CNY 货期 数量
1 mg ¥ 167 现货
5 mg ¥ 367 现货
10 mg ¥ 592 现货
25 mg ¥ 928 现货
50 mg ¥ 1,230 现货
100 mg ¥ 1,650 现货
200 mg ¥ 2,460 现货
500 mg ¥ 3,970 现货
1 mL * 10 mM (in DMSO) ¥ 423 现货
其他形式的 Necrostatin-1:
产品目录号及名称: Necrostatin-1 (T1847)
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选择批次  
纯度: 100%
纯度: 99.81%
纯度: 99.74%
纯度: 99.25%
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生物活性
化学信息
存储 & 溶解度
参考文献
产品描述 Necrostatin-1 (Nec-1) is a necrotic apoptosis inhibitor and RIP1 inhibitor with specificity. Necrostatin-1 inhibits TNF-α-induced necrotic apoptosis. Necrostatin-1 also inhibits IDO.
靶点活性 RIP1:490 nM(EC50, Jurkat cells)
体外活性 方法:人肝癌细胞 Huh7 和 SK-HEP-1 用 Necrostatin-1 (10-20 µM) 预处理 1 h,再用 sulfasalazine、 erastin 或 RSL3 处理24 h,使用 CellTiter Glo® assay 检测细胞活力。
结果:Necrostatin-1 显著阻断了 sulfasalazine 和 erastin 在两种细胞系中诱导的细胞活力下降,部分逆转了 SK-HEP-1 细胞中 RSL3 引起的细胞活力下降。[1]
方法:人组织细胞淋巴瘤细胞 U937 用 Necrostatin-1 (1-20 µM)、zVAD.fmk (100 μM) 和 TNFα (10 ng/mL)处理 72 h,使用 ATP-based viability assay 检测细胞活力。
结果:Necrostatin-1 以浓度依赖的方式有效阻断 U937 细胞的坏死性死亡。[2]
方法:H/R 损伤诱导的人肾乳头瘤状细胞 HK-2 用 Necrostatin-1 (30 mmol/L) 处理 2-12 h,使用 Flow Cytometry 方法分析细胞死亡情况。
结果:Necrostatin-1 部分保护 HK-2 细胞免受 H/R 诱导的坏死。[3]
体内活性 方法:为研究造影剂诱导的 AKI (CIAKI) 的病理生理学,将 Necrostatin-1 (1.65 mg/kg) 单次腹腔注射给 C57BL/6 小鼠,15 min 后使用放射性造影剂 (RCM) 诱导 CIAKI。
结果:Necrostatin-1 可以预防渗透性肾病和 CIAKI。Necrostatin-1 阻止了 RCM 诱导的管周毛细血管扩张,这表明 RIP1 激酶结构域在调节 CIAKI 的微血管血液动力学和病理生理学中具有与细胞死亡无关的新作用。[4]
方法:为研究对小鼠肝炎的保护作用及其机制,将 Necrostatin-1 (1.8 mg/kg) 单次腹腔注射给C57BL/6 小鼠,1 h 后使用 concanavalin A 诱导 肝炎。
结果:注射 Necrostatin-1 的小鼠中观察到肝功能和组织病理学变化的改善以及炎症细胞因子产生的抑制。注射 Necrostatin-1 的小鼠中 TNF-α、IFN-γ、IL2、IL6 和 RIP1 的表达显著降低。Necrostatin-1 处理显著减少了自噬体的形成。结果表明,Necrostatin-1 通过 RIP1 相关和自噬相关途径预防 concanavalin A 诱导的肝损伤。[5]
激酶实验 The assay was performed essentially as described. 293T cells were transfected with pcDNA3-FLAG-RIP1 vector, vectors encoding RIP1 mutant proteins or pcDNA3-RIP2-Myc and pcDNA3-FLAG-RIP3 vectors using standard Ca3(PO4)2 precipitation procedure. Culture medium was replaced 6 h after the transfection and cells were lysed 48 h later in the TL buffer consisting of 1% Triton X-100, 150 mM NaCI, 20 mM HEPES, pH 7.3, 5 mM EDTA, 5 mM NaF, 0.2 mM NaVO3 and complete protease inhibitor cocktail. Immunoprecipitation was carried out for 16 h at 4 °C using anti-FLAG M2 agarose beads, followed by three washes with TL buffer and two washes with 20 mM HEPES, pH 7.3. Beads were incubated in 15 μl of the reaction buffer containing 20 mM HEPES, pH 7.3, 10 mM MnCl2 and 10 mM MgCl2 for 15 min at 23–25 °C in the presence of different concentrations of necrostatins. For these assays, compound stocks (in DMSO) were diluted to appropriate concentrations in DMSO before the addition to the reactions to maintain final concentration of DMSO for all samples at 3%. Kinase reaction was initiated by addition of 10 μM cold ATP and 1 mCi of [γ-32P] ATP, and reactions were carried out for 30 min at 30 °C. Reactions were stopped by boiling in SDS-PAGE sample buffer and subjected to 8% SDS-PAGE. RIP1 band was visualized by analysis in a Storm 8200 Phosphorimager. Similar protocol was used for endogenous RIP1 kinase reactions, except mouse monoclonal RIP1 antibody and protein magnetic beads or rabbit RIP1 antibody-coupled agarose beads were used. For recombinant baculovirally expressed RIP1, protein was expressed in Sf9 cells according to manufacturer's instructions and purified using glutathione-sepharose beads. Protein was eluted in 50 mM Tris-HCl, pH 8.0 supplemented with 10 mM reduced glutathione, and eluted protein was used in the kinase reactions, supplemented with 5 × kinase reaction buffer (100 mM HEPES, pH 7.3, 50 mM MnCl2, 50 mM MgCl2, 50 μM cold ATP and 5 μCi of [γ-32P]ATP) [1].
细胞实验 Determination of EC50 was performed in FADD-deficient Jurkat cells treated with human TNFα as previously described. Briefly, cells were seeded into 96-well plates and treated with a range of necrostatin concentrations (30 nM to 100 μM, 11 dose points) in the presence and absence of 10 ng ml–1 human TNFα for 24 h. For these and all other cellular assays, compound stocks (in DMSO) were diluted to appropriate concentrations in DMSO before addition to the cells to maintain final concentration of DMSO for all samples at 0.5%. Cell viability was determined using CellTiter-Glo luminescent cell viability assay. Ratio of luminescence in compound and TNF-treated wells to compound-treated, TNF-untreated wells was calculated (viability, %) [1].
动物实验 24 hours after reperfusion, mice received intravenous application of 200 μl PBS or RCM via the tail vein. A single dose of zVAD (10 mg/kg body weight) or Nec-1 (1.65 mg/kg body weight) was applied intraperitoneally 15 min. before RCM-injection. To test the activity of zVAD, we applied zVAD from the same byculture to anti-Fas-treated Jurkat cells to assure its quality before mice were treated with this compound. Mice were harvested another 24 hours after RCM-application (48 hours after reperfusion). Blood samples were obtained from retroorbital bleeding and serum levels of urea and creatinine 5 were determined according to clinical standards in the central laboratory of the University Hospital Schleswig-Holstein, Campus Kiel, Germany, employing an enzymatic ultraviolettest for urea and an enzymatic peroxidase-dependent test for creatinine according to the manufacturer's instructions. Kidneys were conserved for histology. In addition to the demonstrated experiments, we compared the PBS group to mice that only received IRI without 200 μl of PBS and detected no changes in serum concentrations of urea and creatinine or histologically [3].
别名 Nec-1, Necrostatin 1
化合物与蛋白结合的复合物

T1847_1

Crystal structure of RIP1 kinase in complex with necrostatin-1 analog

分子量 259.33
分子式 C13H13N3OS
CAS No. 4311-88-0

存储

Powder: -20°C for 3 years | In solvent: -80°C for 1 year

溶解度

DMSO: 40 mg/mL (154.24 mM)

溶液配制表

可选溶剂 浓度 体积 质量 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 3.8561 mL 19.2805 mL 38.5609 mL 96.4023 mL
5 mM 0.7712 mL 3.8561 mL 7.7122 mL 19.2805 mL
10 mM 0.3856 mL 1.928 mL 3.8561 mL 9.6402 mL
20 mM 0.1928 mL 0.964 mL 1.928 mL 4.8201 mL
50 mM 0.0771 mL 0.3856 mL 0.7712 mL 1.928 mL
100 mM 0.0386 mL 0.1928 mL 0.3856 mL 0.964 mL

计算器

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稀释计算器
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分子量计算器
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参考文献

1. Hanna Y, et al. Necrostatin-1 Prevents Ferroptosis in a RIPK1- and IDO-Independent Manner in Hepatocellular Carcinoma. Antioxidants. 2021 July;10(9):1347. 2. Degterev A, et al. Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury. Nat Chem Biol. 2005 Jul;1(2):112-9. doi: 10.1038/nchembio711. Epub 2005 May 29. Erratum in: Nat Chem Biol. 2005 Sep;1(4):234. 3. Shen B, et al. Necrostatin-1 Attenuates Renal Ischemia and Reperfusion Injury via Meditation of HIF-1α/mir-26a/TRPC6/PARP1 Signaling. Mol Ther Nucleic Acids. 2019 Sep 6;17:701-713. 4. Linkermann A, et al. The RIP1-kinase inhibitor necrostatin-1 prevents osmotic nephrosis and contrast-induced AKI in mice. J Am Soc Nephrol. 2013 Oct;24(10):1545-57. 5. Zhou Y, et al. Protective effects of necrostatin-1 against concanavalin A-induced acute hepatic injury in mice. Mediators Inflamm. 2013;2013:706156. 6. hang C, Liu Z, Zhang Y, et al. Z“Iron free” zinc oxide nanoparticles with ion-leaking properties disrupt intracellular ROS and iron homeostasis to induce ferroptosis[J]. Cell Death & Disease. 2020, 11(3): 1-15. 7. Yao X, Ma S, Peng S, et al. Zwitterionic Polymer Coating of Sulfur Dioxide‐Releasing Nanosystem Augments Tumor Accumulation and Treatment Efficacy[J]. Advanced Healthcare Materials. 2020, 9(5): 1901582. 9. Wang S, Li F, Qiao R, et al. Arginine-Rich Manganese Silicate Nanobubbles as a Ferroptosis-Inducing Agent for Tumor-Targeted Theranostics[J]. ACS nano. 2018 Dec 26;12(12):12380-12392. 10. Yan B, Ai Y, Sun Q, et al. Membrane Damage during Ferroptosis Is Caused by Oxidation of Phospholipids Catalyzed by the Oxidoreductases POR and CYB5R1[J]. Molecular Cell. 2020

文献引用

1. Hu G, Cui Z, Chen X, et al.Suppressing Mesenchymal Stromal Cell Ferroptosis Via Targeting a Metabolism‐Epigenetics Axis Corrects their Poor Retention and Insufficient Healing Benefits in the Injured Liver Milieu.Advanced Science.2023: 2206439. 2. Li Y, Yang W, Zheng Y, et al.Targeting fatty acid synthase modulates sensitivity of hepatocellular carcinoma to sorafenib via ferroptosis.Journal of Experimental & Clinical Cancer Research.2023, 42(1): 1-19. 3. Wang X, Ji Y, Qi J, et al.Mitochondrial carrier 1 (MTCH1) governs ferroptosis by triggering the FoxO1-GPX4 axis-mediated retrograde signaling in cervical cancer cells.Cell Death & Disease.2023, 14(8): 1-13. 4. Lei S, Chen C, Han F, et al.AMER1 deficiency promotes the distant metastasis of colorectal cancer by inhibiting SLC7A11-and FTL-mediated ferroptosis.Cell Reports.2023, 42(9). 5. Zhou R, You Y, Zha Z, et al.Biotin decorated celastrol-loaded ZIF-8 nano-drug delivery system targeted epithelial ovarian cancer therapy.Biomedicine & Pharmacotherapy.2023, 167: 115573. 6. Zhu X, Huang N, Ji Y, et al.Brusatol induces ferroptosis in oesophageal squamous cell carcinoma by repressing GSH synthesis and increasing the labile iron pool via inhibition of the NRF2 pathway.Biomedicine & Pharmacotherapy.2023, 167: 115567. 7. Li H, Guan J, Chen J, et al.Necroptosis signaling and NLRP3 inflammasome cross-talking in epithelium facilitate Pseudomonas aeruginosa mediated lung injury.Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease.2022: 166613. 8. Wu Z, Lin C, Zhang F, et al.TIGD1 Function as a Potential Cuproptosis Regulator Following a Novel Cuproptosis-Related Gene Risk Signature in Colorectal Cancer.Cancers.2023, 15(8): 2286. 9. Huang F, Liang J, Lin Y, et al.Repurposing of Ibrutinib and Quizartinib as potent inhibitors of necroptosis.Communications Biology.2023, 6(1): 972. 10. Cai H, Qin D, Liu Y, et al.Remodeling of Gut Microbiota by Probiotics Alleviated Heat Stroke‐Induced Necroptosis in Male Germ Cells.Molecular Nutrition & Food Research.2023: 2300291.
11. Zeng H, Xie H, Ma Q, et al.Identification of N-(3-(methyl (3-(orotic amido) propyl) amino) propyl) oleanolamide as a novel topoisomerase I catalytic inhibitor by rational design, molecular dynamics simulation, and biological evaluation.Bioorganic Chemistry.2023: 106734. 12. Du S, Zeng F, Sun H, et al. Prognostic and therapeutic significance of a novel ferroptosis related signature in colorectal cancer patients. Bioengineered. 2022, 13(2): 2498-2512. 13. Ning X, Qi H, Yuan Y, et al. Identification of a new small molecule that initiates ferroptosis in cancer cells by inhibiting the system Xc− to deplete GSH. European Journal of Pharmacology. 2022: 175304. 14. Wang S, Li F, Qiao R, et al. Arginine-Rich Manganese Silicate Nanobubbles as a Ferroptosis-Inducing Agent for Tumor-Targeted Theranostics. ACS nano. 2018 Dec 26;12(12):12380-12392. 15. Su G, Yang W, Wang S, et al. SIRT1-autophagy axis inhibits excess iron-induced ferroptosis of foam cells and subsequently increases IL-1Β and IL-18. Biochemical and Biophysical Research Communications. 2021, 561: 33-39. 16. Wu X, Lu Y, Qin X. Combination of Compound Kushen Injection and cisplatin shows synergistic antitumor activity in p53-R273H/P309S mutant colorectal cancer cells through inducing apoptosis. Journal of Ethnopharmacology. 2021: 114690. 17. Yao X, Ma S, Peng S, et al. Zwitterionic Polymer Coating of Sulfur Dioxide‐Releasing Nanosystem Augments Tumor Accumulation and Treatment Efficacy. Advanced Healthcare Materials. 2020, 9(5): 1901582. 18. Wang F, Xie M, Chen P, et al. Homoharringtonine combined with cladribine and aclarubicin (HCA) in acute myeloid leukemia: A new regimen of conventional drugs and its mechanism. Oxidative Medicine and Cellular Longevity. 2022 19. Yang W, Liu S, Li Y, et al. Pyridoxine induces monocyte-macrophages death as specific treatment of acute myeloid leukemia. Cancer Letters. 2020 20. Ni H, Qin H, Sun C, et al. MiR-375 reduces the stemness of gastric cancer cells through triggering ferroptosis. Stem Cell Research & Therapy. 2021, 12(1): 1-17. 21. Zhang Y, Fan B Y, Pang Y L, et al. Neuroprotective effect of deferoxamine on erastininduced ferroptosis in primary cortical neurons. Neural Regeneration Research. 2020, 15(8): 1539 22. Yan B, Ai Y, Sun Q, et al. Membrane Damage during Ferroptosis Is Caused by Oxidation of Phospholipids Catalyzed by the Oxidoreductases POR and CYB5R1. Molecular Cell. 2020 23. hang C, Liu Z, Zhang Y, et al. Z“Iron free” zinc oxide nanoparticles with ion-leaking properties disrupt intracellular ROS and iron homeostasis to induce ferroptosis. Cell Death & Disease. 2020, 11(3): 1-15. 24. Yang K H, Tang J Y, Chen Y N, et al. Nepenthes Extract Induces Selective Killing, Necrosis, and Apoptosis in Oral Cancer Cells. Journal of Personalized Medicine. 2021, 11(9): 871. 25. D’Onofrio N, Martino E, Balestrieri A, et al. Diet‐derived ergothioneine induces necroptosis in colorectal cancer cells by activating the SIRT3/MLKL pathway. FEBS letters. 2022 26. Wu H, Cheng X, Huang F, et al. Aprepitant Sensitizes Acute Myeloid Leukemia Cells to the Cytotoxic Effects of Cytosine Arabinoside in vitro and in vivo. Development and Therapy. 2020, 14: 2413 27. Wang Z, Zou F, Wang A, et al. Repurposing of the FGFR inhibitor AZD4547 as a potent inhibitor of necroptosis by selectively targeting RIPK1. Acta Pharmacologica Sinica. 2022: 1-10 28. Wang Y, Zhang B, Liu S, et al.The traditional herb Sargentodoxa cuneata alleviates DSS-induced colitis by attenuating epithelial barrier damage via blocking necroptotic signaling.Journal of Ethnopharmacology.2023: 117373. 29. Chen H, Hu J, Xiong X, et al.AURKA inhibition induces Ewing’s sarcoma apoptosis and ferroptosis through NPM1/YAP1 axis.Cell Death & Disease.2024, 15(1): 99. 30. Li J, Liu X, Liu Y, et al.Saracatinib inhibits necroptosis and ameliorates psoriatic inflammation by targeting MLKL.Cell Death & Disease.2024, 15(2): 122. 31. Chen J, Liu Y, You Y, et al.Biotin-decorated celastrol-loaded ZIF-8 nanoparticles induce ferroptosis for colorectal cancer therapy.Materials & Design.2024: 112814.
收起
GSK481 RIPK2/3-IN-1 Tuxobertinib Zharp2-1 GSK840 HS-1371 Necrostatin-34 GSK-843

相关化合物库

该产品包含在如下化合物库中:
代谢化合物库 经典已知活性库 激酶抑制剂库 肿瘤免疫治疗小分子化合物库 抗癌细胞代谢库 表型筛选靶点鉴定库 细胞凋亡化合物库 血脑屏障通透化合物库 抗乳腺癌化合物库 已知活性化合物库

剂量换算

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体内实验配液计算器

请在以下方框中输入您的动物实验信息后点击计算,可以得到母液配置方法和体内配方的制备方法: 比如您的给药剂量是10 mg/kg,每只动物体重20 g,给药体积100 μL,一共给药动物10 只,您使用的配方为5% DMSO+30% PEG300+5% Tween 80+60% ddH2O。那么您的工作液浓度为2 mg/mL。

母液配置方法:2 mg 药物溶于 50 μL DMSO (母液浓度为 40 mg/mL), 如您需要配置的浓度超过该产品的溶解度,请先与我们联系。

体内配方的制备方法:取 50 μL DMSO 主液,加入 300 μL PEG300, 混匀澄清,再加 50 μL Tween 80,混匀澄清,再加 600 μL ddH2O, 混匀澄清。

第一步:请输入动物实验的基本信息
剂量
mg/kg
每只动物体重
g
给药体积
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第二步:请输入动物体内配方组成,不同的产品配方组成不同,如有配方需求,可先联系我们提供正确的体内配方。
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技术支持

您可能有的问题的答案可以在抑制剂处理说明中找到,包括如何准备库存溶液,如何存储产品,以及基于细胞的分析和动物实验需要特别注意的问题。

Keywords

Necrostatin-1 4311-88-0 Apoptosis Autophagy Metabolism NF-Κb Indoleamine 2,3-Dioxygenase (IDO) Ferroptosis RIP kinase Receptor-interacting protein kinases Inhibitor RIPK Nec 1 Necrostatin1 Nec1 Nec-1 inhibit Necrostatin 1 inhibitor

 

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