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Necrosulfonamide

Catalog No.
B7731
Necroptosis inhibitor
Grouped product items
SizePriceStock Qty
10mg
$65.00
In stock
50mg
$200.00
In stock
For scientific research use only and should not be used for diagnostic or medical purposes.

Tel: +1-832-696-8203

Email: [email protected]

Worldwide Distributors

Background

Necrosulfonamide (NSA) is a pharmacological inhibitor of mixed lineage kinase-like protein (MLKL) [1]. NSA is potent in protecting necrotic/necroptotic death of human HT-29 with an IC50 value of 124 nM [2].

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 [3].

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 [1]. 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 [4]. 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 [3].

Pharmacological treatment with NSA delayed cone degeneration [5].

References:
[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.

Product Citation

Chemical Properties

Physical AppearanceA crystalline solid
StorageStore at -20°C
M.Wt461.47
Cas No.1360614-48-7
FormulaC18H15N5O6S2
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
SDFDownload SDF
Canonical SMILESO=S(NC1=NC=CN=C1OC)(C(C=C2)=CC=C2NC(/C=C\C3=CC=C([N+]([O-])=O)S3)=O)=O
Shipping ConditionSmall Molecules with Blue Ice, Modified Nucleotides with Dry Ice.
General tips We do not recommend long-term storage for the solution, please use it up soon.

Protocol

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.

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