Necrosulfonamide
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.
Necrosulfonamide(NSA)是混合谱系激酶样蛋白(MLKL)的药理学抑制剂[1]。NSA可以有效防止人类HT-29的坏死性死亡,IC50值为124 nM [2]。
MLKL是功能性RIP3的底物,可以通过其激酶样结构域结合RIP3,但它缺乏激酶活性。MLKL的T357和S358位点可被RIP3磷酸化[3]。
使用NSA单独处理不能阻止细胞死亡,而NSA可以显著增强zVAD.fmk对BV6/5AC诱导的细胞死亡的保护作用。同时,在同一细胞系中,在不存在zVAD.fmk的情况下,MLKL基因敲减不能显著保护细胞免受BV6/5AC的影响[1]。在Dox处理的HeLa细胞中,NSA抑制坏死。在高浓度RIP3存在时,细胞可以克服necrostatin-1对RIP1的变构抑制。相比之下,NSA有效地防止这种情况下的细胞坏死。同样地,MLKL敲减也可以阻断坏死。在诱导坏死的条件下,NSA使管状线粒体形态保持正常。MLKL基因敲减也可以阻止线粒体的形态变化[4]。在非RIP3表达的Panc-1细胞中,5 μM的NSA对TNF-α以及Smac模拟物诱导的细胞凋亡没有影响。在NSA存在时,观察到离散的RIP3,但未能检测到大的RIP3,这意味着NSA可以作用于坏死途径的特定步骤,阻止坏死[3]。
NSA的药理学治疗可以延迟视锥细胞退化[5]。
参考文献:
[1]. Gerges S, Rohde K, Fulda S. Cotreatment with Smac mimetics and demethylating agents induces both apoptotic and necroptotic cell death pathways in acute lymphoblastic leukemia cells[J]. Cancer letters, 2016, 375(1): 127-132.
[2]. Bae JH, Shim JH, Cho YS. Chemical regulation of signaling pathways to programmed necrosis[J]. Archives of pharmacal research, 2014, 37(6): 689-697.
[3]. Wang H, Sun L, Su L, et al. Mixed lineage kinase domain-like protein MLKL causes necrotic membrane disruption upon phosphorylation by RIP3[J]. Molecular cell, 2014, 54(1): 133-146.
[4]. Wang Z, Jiang H, Chen S, et al. The mitochondrial phosphatase PGAM5 functions at the convergence point of multiple necrotic death pathways[J]. Cell, 2012, 148(1): 228-243.
[5]. Viringipurampeer IA, Mohammadi Z, Shan X, et al. Rip3 knockdown rescues photoreceptor cell death in pde6c zebrafish model of achromatopsia[J]. Investigative Ophthalmology & Visual Science, 2013, 54(15): 5955-5955.
- 1. 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
- 2. Qi Wang, Yaxun Guo, et al. "RNA binding protein DAZAP1 promotes HCC progression and regulates ferroptosis by interacting with SLC7A11 mRNA." Exp Cell Res. 2021 Feb 1;399(1):112453. PMID:33358859
- 3. Nneka Elizabeth Mbah. "Defining the Mechanism of Methuosis, a Non-apoptotic Cell Death Pathway, Induced by Indolyl Chalcone Compounds in Glioblastoma Cells." The University of Toledo.December 2016.
Physical Appearance | A crystalline solid |
Storage | Store at -20°C |
M.Wt | 461.47 |
Cas No. | 1360614-48-7 |
Formula | C18H15N5O6S2 |
Solubility | ≥46.1 mg/mL in DMSO; insoluble in EtOH; insoluble in H2O |
Chemical Name | (Z)-N-(4-(N-(3-methoxypyrazin-2-yl)sulfamoyl)phenyl)-3-(5-nitrothiophen-2-yl)acrylamide |
SDF | Download SDF |
Canonical SMILES | O=S(NC1=NC=CN=C1OC)(C(C=C2)=CC=C2NC(/C=C\C3=CC=C([N+]([O-])=O)S3)=O)=O |
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。 |
Cell experiment:[1] | |
Cell lines |
Human colorectal cancer HT-29 cells |
Reaction Conditions |
1 μM necrosulfonamide for 8 or 12 h incubation |
Applications |
Necrosulfonamide treatment (1 μM; 8 or 12 h incubation) completely blocked necroptosis by disturbing MLKL-induced liposome leakage in HT-29 cells treated with T/S/Z. Although necrosulfonamide did not prevent MLKL phosphorylation, it was able to block p-MLKL translocation to the membrane fraction in HT-29 cells subjected to T/S/Z treatment. Necrosulfonamide was used to explore the role of MLKL in membrane integrity and necrotic death. |
Note |
The technical data provided above is for reference only. |
References: 1. Wang H, Sun L, Su L, et al. Mixed lineage kinase domain-like protein MLKL causes necrotic membrane disruption upon phosphorylation by RIP3. Molecular Cell, 2014, 54(1): 133-146. |
质量控制和MSDS
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