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.
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
Necrosulfonamide (NSA) is a pharmacological inhibitor of mixed lineage kinase-like protein (MLKL) . NSA is potent in protecting necrotic/necroptotic death of human HT-29 with an IC50 value of 124 nM .
MLKL, a functional RIP3 substrate, can bind to RIP3 through its kinase-like domain but it lacks kinase activity. MLKL can be phosphorylated by RIP3 at the T357 and S358 sites .
Treatment with NSA alone did not rescue cell death, while NSA significantly enhanced the protection of zVAD.fmk against BV6/5AC-induced cell death. In the same line, knockdown of MLKL did not significantly protect cells against BV6/5AC cotreatment in the absence of zVAD.fmk . In the Dox-treated HeLa cells, NSA inhibited necrosis. With a higher level of RIP3, the allosteric inhibition of necrostatin-1 on RIP1 was overcome by cells. In contrast, NSA still efficiently prevented necrosis under this condition. Consistently, knockdown of MLKL also blocked necrosis. Under necrosis-inducing conditions, the presence of NSA made tubular mitochondrial morphology remain normal. Consistently the mitochondrial morphological changes were also prevented by the knockdown of MLKL . Even at 5 μM concentration, NSA had no effect on the apoptosis induced by TNF-α plus Smac mimetic in non-RIP3-expressing Panc-1 cells. In the presence of NSA, the discrete RIP3 punctae were detected but failed to enlarge. That meant NSA blocked necrosis at a specific step in the necrosis pathway .
Pharmacological treatment with NSA delayed cone degeneration .
. 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.
. Bae JH, Shim JH, Cho YS. Chemical regulation of signaling pathways to programmed necrosis[J]. Archives of pharmacal research, 2014, 37(6): 689-697.
. 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.
. 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.
. 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. 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|
|Solubility||≥46.1 mg/mL in DMSO; insoluble in EtOH; insoluble in H2O|
|Shipping Condition||Evaluation sample solution: ship with blue ice. All other available sizes: ship with RT, or blue ice upon request.|
|General tips||For obtaining a higher solubility, please warm the tube at 37°C and shake it in the ultrasonic bath for a while. Stock solution can be stored below -20°C for several months.|
Human colorectal cancer HT-29 cells
1 μM necrosulfonamide for 8 or 12 h incubation
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.
The technical data provided above is for reference only.
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.
Quality Control & MSDS
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