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Necroptosis inhibitor
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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].

[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
Cas No.1360614-48-7
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 ConditionEvaluation sample solution: ship with blue ice. All other available sizes: ship with RT, or blue ice upon request.
General tipsFor 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.


Cell experiment:[1]

Cell lines

Human colorectal cancer HT-29 cells

Reaction Conditions

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

Chemical structure


Related Biological Data


Related Biological Data