Necrostatin-34 (Nec-34), a RIPK1 kinase inhibitor, stabilizes RIPK1 kinase in an inactive conformation by occupying a distinct binding pocket in the kinase domain[1].
体外研究 (In Vitro)
Necrostatin-34 (Nec-34) exhibits IC50 values of 667 nM and 134 nM for TNFα in FADD def-Jurkat cells and L939 cells, respectively[1]. Necrostatin-34 (Nec-34, 10 μM) inhibits the dimerization-induced RIPK1 activation as examined by phosphorylation of Ser166 (p-S166) of RIPK1, a biomarker for RIPK1 activation[1]. Necrostatin-34 (Nec-34) may block TNFα-induced complex II formation by inhibiting the activation of RIPK1 kinase[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Western Blot Analysis[1]
Cell Line:
RIPK1 knockout L929 cells transfected with an expressing vector encoding an inducible and dimerizable RIPK1 fused with FKBP at the C-terminus.
Concentration:
10 μM.
Incubation Time:
30 min (and then 100 ng/mL TNFα was added for indicated periods of time).
Result:
Downregulated p-S166 levels.
分子量
384.48
Formula
C18H16N4O2S2
CAS 号
375835-43-1
运输条件
Room temperature in continental US; may vary elsewhere.
Necrostatin 2 S enantiomer 是 Necrostatin 2 的 S 型异构体。Necrostatin 2 是高活性的坏死性凋亡抑制剂，为有效的 RIPK1 抑制剂，缺乏 IDO 靶向作用。
Necrostatin 2 S enantiomer Chemical Structure
CAS No. : 852391-20-9
规格
价格
是否有货
数量
10 mM * 1 mL in DMSO
￥2291
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1 mg
￥750
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5 mg
￥2000
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10 mg
￥3660
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50 mg
￥9900
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100 mg
询价
200 mg
询价
* Please select Quantity before adding items.
Necrostatin 2 S enantiomer 相关产品
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生物活性
Necrostatin 2 S enantiomer is the S enantiomer of Necrostatin 2. Necrostatin 2 is a potent necroptosis inhibitor, acts as a RIPK1 inhibitor lacking the IDO-targeting effect. Target: RIPK1 [4] Necrostatin 2 is a potent in vitro necroptosis inhibitors (exemplified by 1, EC50-0.05 uM) that also were efficacious in an animal model of ischemic stroke. Many Necroptosis inhibitor derivatives are designed for researchers. Necroptosis is a regulated caspase-independent cell death mechanism that results in morphological features resembling necrosis. It can be induced in a FADD-deficient variant of human Jurkat T cells treated with TNF-a. 5-(1H-Indol-3-ylmethyl)-2-thiohydantoins and 5-(1H-indol-3-ylmethyl)hydantoins were found to be potent necroptosis inhibitors (called necrostatins).
分子量
277.71
Formula
C13H12ClN3O2
CAS 号
852391-20-9
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Teng X, Keys H, Jeevanandam A, Structure-activity relationship study of [1,2,3]thiadiazole necroptosis inhibitors. Bioorg Med Chem Lett. 2007 Dec 15;17(24):6836-40.
[2]. Takahashi N, et al. Necrostatin-1 analogues: critical issues on the specificity, activity and in vivo use in experimental disease models. Cell Death Dis. 2012 Nov 29;3:e437.
[3]. Jagtap PG, Degterev A, Choi S, Structure-activity relationship study of tricyclic necroptosis inhibitors. J Med Chem. 2007 Apr 19;50(8):1886-95.
[4]. Teng X, Degterev A, Jagtap P, Structure-activity relationship study of novel necroptosis inhibitors. Bioorg Med Chem Lett. 2005 Nov 15;15(22):5039-44.
Necrotatin-7 (Nec-7) is a potent necroptosis inhibitor with an EC50 of 10.6 μM. Necrotatin-7 does not inhibit recombinant RIP1 kinase[1].
分子量
371.41
Formula
C16H10FN5OS2
CAS 号
351062-08-3
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Weihong Zheng, et al. Structure-activity relationship study of a novel necroptosis inhibitor, necrostatin-7. Bioorg Med Chem Lett. 2008 Sep 15;18(18):4932-5.
Necrotatin-7 (Nec-7) is a potent necroptosis inhibitor with an EC50 of 10.6 μM. Necrotatin-7 does not inhibit recombinant RIP1 kinase[1].
分子量
371.41
Formula
C16H10FN5OS2
CAS 号
351062-08-3
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Weihong Zheng, et al. Structure-activity relationship study of a novel necroptosis inhibitor, necrostatin-7. Bioorg Med Chem Lett. 2008 Sep 15;18(18):4932-5.
Necrotatin-7 (Nec-7) is a potent necroptosis inhibitor with an EC50 of 10.6 μM. Necrotatin-7 does not inhibit recombinant RIP1 kinase[1].
分子量
371.41
Formula
C16H10FN5OS2
CAS 号
351062-08-3
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Weihong Zheng, et al. Structure-activity relationship study of a novel necroptosis inhibitor, necrostatin-7. Bioorg Med Chem Lett. 2008 Sep 15;18(18):4932-5.
Necrostatin-1 (Nec-1) is a potent necroptosis inhibitor with an EC50 of 490 nM in Jurkat cells. Necrostatin-1 inhibits RIP1 kinase (EC50=182 nM). Necrostatin-1 is also an IDO inhibitor[1].
IC50 & Target
EC50: 182 nM (RIP1 kinase)[1]
体外研究 (In Vitro)
Necrostatin-1 (Nec-1) efficiently inhibits the TNFα-induced necrotic death of L929 cells, which does not require exogenous caspase inhibitors[1]. Necrostatin-1 (Nec-1) prevents radiocontrast media (RCM)-induced dilation of peritubular capillaries, suggesting a novel role unrelated to cell death for the RIP1 kinase domain in the regulation of microvascular hemodynamics and pathophysiology of contrast-induced AKI (CIAKI)[2]. Necrostatin-1 (Nec-1) (30 µM) increases the survival of cardiomyocyte progenitor cell (CMPCs) by inhibiting necrotic cell death[4].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
Necrostatin-1 (Nec-1) induces tubular bilation and affects the kinetics of the dilation of peritubular capillaries after RCM application. Upon a single intraperitoneal application of a single dose of Necrostatin-1 (1.65 mg/kg body weight, i.p.) 15 minutes before RCM, the return to baseline levels is prevented within the observation period[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
259.33
Formula
C13H13N3OS
CAS 号
4311-88-0
运输条件
Room temperature in continental US; may vary elsewhere.
Solubility: 1.67 mg/mL (6.44 mM); Suspended solution; Need ultrasonic
*以上所有助溶剂都可在 上海金畔生物科技有限公司 网站选购。
参考文献
[1]. 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.
[2]. 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.
[3]. Huang C, et al. Shikonin kills glioma cells through necroptosis mediated by RIP-1. PLoS One. 2013 Jun 28;8(6):e66326.
[4]. Feyen D, et al. Increasing short-term cardiomyocyte progenitor cell (CMPC) survival by necrostatin-1 did not further preserve cardiac function. Cardiovasc Res. 2013 Jul 1;99(1):83-91.
[5]. Zhou K, et al. RIP1-RIP3-DRP1 pathway regulates NLRP3 inflammasome activation following subarachnoid hemorrhage. Exp Neurol. 2017 Sep;295:116-124.
Cell Assay [3]
C6 (3×105 cells/well) and U87 (1.5×105 cells/well) glioma cells are seeded onto 96-well microplate and cultured 24 h. PBS is added into the control group and Shikonin is added into experimental group to reach the final concentration. Cellular viability is assessed using an MTT assay after Shikonin treatment at indicated time point. The absorbance value (A) at 570 nm is read using an automatic multi-well spectrophotometer. Two groups of glioma cells from the same cell line are treated with Shikonin at lower or higher concentration, respectively; other two groups of glioma cells are treated 1 h with 100 µM Necrostatin-1 or 40 µM z-VAD-fmk prior to co-incubation with Shikonin at indicated concentration. Additionally, another two groups of glioma cells are treated only with 100 µM Necrostatin-1 or 40 µM Z-VAD-fmk at corresponding time point[3].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration
Mice[2] 8-10 week old male C57BL/6 mice (average weight approx.23 g) are used. Mice receive intravenous application of 200 μL PBS or radiocontrast media (RCM) via the tail vein. A single dose of Z-VAD-fmk (10 mg/kg body weight) or Necrostatin-1 (1.65 mg/kg body weight) is applied intraperitoneally 15 min. before RCM-injection. Mice are harvested another 24 hours after RCM-application (48 hours after reperfusion). Blood samples are obtained from retroorbital bleeding and serum levels of urea and creatinine are determined.
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. 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.
[2]. 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.
[3]. Huang C, et al. Shikonin kills glioma cells through necroptosis mediated by RIP-1. PLoS One. 2013 Jun 28;8(6):e66326.
[4]. Feyen D, et al. Increasing short-term cardiomyocyte progenitor cell (CMPC) survival by necrostatin-1 did not further preserve cardiac function. Cardiovasc Res. 2013 Jul 1;99(1):83-91.
[5]. Zhou K, et al. RIP1-RIP3-DRP1 pathway regulates NLRP3 inflammasome activation following subarachnoid hemorrhage. Exp Neurol. 2017 Sep;295:116-124.
[1]. Takahashi N, et al. Necrostatin-1 analogues: critical issues on the specificity, activity and in vivo use in experimental disease models. Cell Death Dis. 2012 Nov 29;3:e437.
Necrostatin 2 is a potent necroptosis inhibitor. EC50 for inhibition of necroptosis in FADD-deficient Jurkat T cells treated with TNF-α is 0.05 μM. Necrostatin 2 is also a RIPK1 inhibitor.
IC50 & Target
Necroptosis[1], RIPK1[4]
体外研究 (In Vitro)
Evaluation of necroptosis inhibitory activity is performed using a FADD-deficient variant of human Jurkat T cells treated with TNF-α. Utilizing these conditions the cells efficiently undergo necroptosis, which is completely and selectively inhibited by Necrostatin 2 (EC50=50 nM). Necrostatin 2 shows activity in a broad range of necroptosis cellular systems[1]. Necrostatin 2 at 30 μM completely protects L929 cells from TNF-α-induced necroptosis. In addition to TNF-α, the pan-caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD.fmk) has also been found to induce necrosis in L929 cells, which is efficiently inhibited by Necrostatin 2[2]. EC50 for inhibition of necroptosis in FADD-deficient Jurkat T cells treated with TNF-α is 0.05 μM[3].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
277.71
Formula
C13H12ClN3O2
CAS 号
852391-19-6
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Teng X, et al. Structure-activity relationship study of [1,2,3]thiadiazole necroptosis inhibitors. Bioorg Med Chem Lett. 2007 Dec 15;17(24):6836-40.
[2]. Jagtap PG, et al. Structure-activity relationship study of tricyclic necroptosis inhibitors. J Med Chem. 2007 Apr 19;50(8):1886-95.
[3]. Teng X, et al. Structure-activity relationship study of novel necroptosis inhibitors. Bioorg Med Chem Lett. 2005 Nov 15;15(22):5039-44.
[4]. Takahashi N, et al. Necrostatin-1 analogues: critical issues on the specificity, activity and in vivo use in experimental disease models. Cell Death Dis. 2012 Nov 29;3:e437.
Kinase Assay [2]
Evaluation of necroptosis inhibitory activity is performed using an FADD-deficient variant of human Jurkat T cells treated for 24 h with TNF-α. Under these conditions the cells underwent necroptosis (the DMSO control had ~40% viability), which is inhibited by Necrostatin 2 (EC50=0.21±0.2 μM) as a positive control. For EC50 value determinations, cells are treated with 10 ng/mL human TNF-α in the presence of increasing concentrations of test compounds (0.029, 0.058, 0.12, 0.23, 0.46, 0.93, 1.9, 3.7, 11.1, 33, and 100 μM) in duplicate for 24 h followed by ATP-based viability assessment. EC50 values±SD are determined from at least two independent experiments[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Assay [2]
L929 cells (100000 cells/mL, 100 μL/well in a 96-well plate) are treated with 10 ng/mL human TNF-α or 100 μM zVAD.fmk in the presence of DMSO (control), 30 μM Necrostatin 2, or 8for 24 h at 37°C in a humidified incubator with 5% CO2 followed by ATP-based viability assessment as described in the previous experiment. Stock solutions (30 mM) in DMSO are initially prepared and then diluted with DMSO to give testing solutions. Each sample is done in duplicate. The final DMSO concentration is 0.5%. Cell viability values are adjusted to account for nonspecific toxicity, which in most cases is <10%. The reported cell viability values (%)±SD are determined from two independent experiments[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Teng X, et al. Structure-activity relationship study of [1,2,3]thiadiazole necroptosis inhibitors. Bioorg Med Chem Lett. 2007 Dec 15;17(24):6836-40.
[2]. Jagtap PG, et al. Structure-activity relationship study of tricyclic necroptosis inhibitors. J Med Chem. 2007 Apr 19;50(8):1886-95.
[3]. Teng X, et al. Structure-activity relationship study of novel necroptosis inhibitors. Bioorg Med Chem Lett. 2005 Nov 15;15(22):5039-44.
[4]. Takahashi N, et al. Necrostatin-1 analogues: critical issues on the specificity, activity and in vivo use in experimental disease models. Cell Death Dis. 2012 Nov 29;3:e437.
