1360614-48-7

Basic information

• Product Name: (E)-N-(4-(N-(3-Methoxypyrazin-2-yl)sulfaMoyl)phenyl)-3-(5-nitrothiophen-2-yl)acrylaMide
• Synonyms: (E)-N-(4-(N-(3-Methoxypyrazin-2-yl)sulfaMoyl)phenyl)-3-(5-nitrothiophen-2-yl)acrylaMide
• CAS NO: 1360614-48-7
• Molecular Formula: C18H15N5O6S2
• Molecular Weight: 461.4716
• Mol File: 1360614-48-7.mol
• Article Data: 1

Chemical Properties

• Appearance: /
• Density: 1.578±0.06 g/cm3(Predicted)
• Storage Temp.: -20°C
• Solubility: Soluble in DMSO (up to 10 mg/ml)
• PKA: 6.37±0.40(Predicted)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 1 month.
• CAS DataBase Reference: (E)-N-(4-(N-(3-Methoxypyrazin-2-yl)sulfaMoyl)phenyl)-3-(5-nitrothiophen-2-yl)acrylaMide(CAS DataBase Reference)
• NIST Chemistry Reference: (E)-N-(4-(N-(3-Methoxypyrazin-2-yl)sulfaMoyl)phenyl)-3-(5-nitrothiophen-2-yl)acrylaMide(1360614-48-7)
• EPA Substance Registry System: (E)-N-(4-(N-(3-Methoxypyrazin-2-yl)sulfaMoyl)phenyl)-3-(5-nitrothiophen-2-yl)acrylaMide(1360614-48-7)

Safety Data

• Hazardous Substances Data: 1360614-48-7(Hazardous Substances Data)

Usage

Description

Necrosulfonamide (1360614-48-7) specifically blocks necroptosis downstream of RIP3 activation by preventing MLKL-RIP3 interaction.1 Displays neuroprotective effects after ischemic brain injury.2 Prevents cystine-starvation-induced necroptosis and ferroptosis in human triple negative breast cancer cells.3 Binds to gasdermin D inhibiting pyroptosis and associated inflammatory cell death and sepsis.4 Rescues cells from TLR3 ligand-induced death.5

Uses

Necrosulfonamide is a necroptosis inhibitor. Necrosulfonamide is a pharmacological inhibitor of mixed lineage kinase domain-like protein (MLKL).

References

1) Sun et al. (2012) Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase; Cell 148 213 2) Zhou et al. (2017) The degradation of mixed linage kinase domain-like protein promotes neuroprotection after ischemic brain injury; Oncotarget, 8 68393 3) Chen et al. (2017) CHAC1 degradation of glutathione enhances cysteine-starvation-induced necroptosis and ferroptosis in human triple negative breast cancer cells via the GCN2-elF2α-ATF4 pathway; Oncotarget, 8 114588 4) Rathkey et al. (2018) Chemical disruption of the pyroptotic pore-forming protein gasdermin D inhibits inflammatory cell death and sepsis; Sci Immunol., 3 eaat2738 5) Cuchet-Lourenco et al. (2018) Biallelic RIPK1 mutations in humans cause severe immunodeficiency, arthritis, and intestinal inflammation; Science, 361 810

Upstream product

• 655-78-7 4-acetylamino-N-(3-methoxy-pyrazin-2-yl)-benzenesulfonamide 
• 4774-10-1 2-amino-3-methoxypyrazine 
• 50868-70-7 (E)-3-(2-nitrothiophen-5-yl)propenoic acid 
• 55785-89-2 (E)-3-(5-nitrothiophen-2-yl)acryloyl chloride 
• 152-47-6 Sulfalen 

Relevant articles and documents

Necrosulfonamide inhibits necroptosis by selectively targeting the mixed lineage kinase domain-like protein

Through high-throughput screening of 200000 compounds and subsequent structure-activity relationship (SAR) studies we identified necrosulfonamide (NSA) as a potent small molecule inhibitor for necroptosis, induced by a combination of TNF-a, Smac mimetic, and z-VAD-fmk (T/S/Z). Applying a forward chemical genetic approach, we utilized an NSA based chemical probe to further reveal that NSA selectively targeted the Mixed Lineage Kinase Domain-like Protein (MLKL) to block the necrosome formation.