| Necrosulfonamide Catalog No.GC10150 |
Sample solution is provided at 25 µL, 10mM.
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Purity = 98.00%
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| Cas No. | 432531-71-0 | SDF | Download SDF |
| Synonyms | N/A | ||
| Chemical Name | (E)-N-[4-[[(3-Methoxy-2-pyrazinyl)amino]sulfonyl]phenyl]-3-(5-nitro-2-thienyl)-2-propenamide | ||
| Canonical SMILES | COC1=NC=CN=C1NS(=O)(=O)C2=CC=C(C=C2)NC(=O)C=CC3=CC=C(S3)[N+](=O)[O-] | ||
| Formula | C18H15N5O6S2 | M.Wt | 461.47 |
| Solubility | ≥46.1mg/mL in DMSO | Storage | Store at -20°C |
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. | ||
| Shipping Condition | Evaluation sample solution : ship with blue ice All other available size: ship with RT , or blue ice upon request |
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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].
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.