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Necrosulfonamide

Catalog No.GC10150

Necrosulfonamida (NSA) es un inhibidor específico de MLKL (proteína similar a quinasa de linaje mixto)[1].

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Necrosulfonamide Chemical Structure

Cas No.: 1360614-48-7

Tamaño Precio Disponibilidad Cantidad
10mM (in 1mL DMSO)
46,00 $
Disponible
5mg
42,00 $
Disponible
10mg
54,00 $
Disponible
25mg
105,00 $
Disponible
50mg
154,00 $
Disponible
100mg
280,00 $
Disponible

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Sample solution is provided at 25 µL, 10mM.

Product has been cited by 2 publications

Product Documents

Quality Control & SDS

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Protocol

Cell experiment [1]:

Cell lines

BMDMs

Preparation Method

IL-1β and LDH levels in the cell supernantant of BMDMs from WT (C57BL/6), Gsdmd-/- and Caspase-1-/- mice primed for 2.5 hr with LPS (50 ng/ml), with necrosulfonamide (NSA) (10 µM) added in the last 30 min of priming, then treated with MSU crystals (300 µg/ml, 6 hr) or nigericin (10 µM, 1 hr).

Reaction Conditions

10 µM; 30 min

Applications

The treatment of LPS primed BMDMs with similar concentrations of NSA, (10 µM) efficiently inhibited MSU crystal-induced IL-1β release in a dose dependent manner.

Animal experiment [2]:

Animal models

Seventy male 8-week-old specific pathogen-free (SPF)-grade C57BL/6J mice weighing 20-25 g

Preparation Method

An ALF (Acute liver failure) model was established by lipopolysaccharide/D-galactosamine challenge in C57BL/6J mice. Necrosulfonamide 20 mg/kg was administered by intraperitoneal injection 30 m before the establishment of the animal model.

Dosage form

20 mg/kg; i.p.

Applications

Pyroptosis was activated in ALF model mice. Mice treated with GSDMD inhibitor Necrosulfonamide developed less severe liver failure. Necrosulfonamide reduced the expression of GSDMD, NLRP3, cleaved caspase-1, cleaved caspase-11, and secretion of interleukin-1 beta in ALF mice model.

References:

[1] Rashidi M, et al. The Pyroptotic Cell Death Effector Gasdermin D Is Activated by Gout-Associated Uric Acid Crystals but Is Dispensable for Cell Death and IL-1β Release. J Immunol. 2019 Aug 1;203(3):736-748.
[2] Wu YL, et al. Gasdermin D Inhibitor Necrosulfonamide Alleviates Lipopolysaccharide/D-galactosamine-induced Acute Liver Failure in Mice. J Clin Transl Hepatol. 2022 Dec 28;10(6):1148-1154.

Background

Necrosulfonamida (NSA) es un inhibidor específico de MLKL (proteína similar a quinasa de linaje mixto). Necrosulfonamida, un inhibidor de GSDMD, podría inhibir la activación del inflamasoma NLRP3 inducida por PPVI.

La prueba de eficacia in vitro mostró que los valores de IC50 para Necrosulfonamida determinados en ensayos celulares de necroptosis (NEC), apoptosis (APOP) o toxicidad (TOX) en células Jurkat y U937 fueron 1399 nM, 6197 nM, 454 nM, >100.000 nM y 14694 nM, respectivamente[3]. In vitro, el tratamiento con 10 µM o 20 µM de Necrosulfonamida inhibió la liberación de IL-1β mediada por GSDMD después de la estimulación del inflamasoma, demostrando una supresión completa de IL-1β incluso después de 60 minutos en células estimuladas con LPS y nigericina[4].

En vivo, se administró Necrosulfonamida a ratones machos adultos C57BL/6 (5 mg/kg intraperitonealmente dos veces al día) y se redujo significativamente el tamaño del hematoma, se suprimieron las células inflamatorias y las citocinas, y se protegió la barrera hematoencefálica en comparación con los controles de vehículo[1]. En vivo, se inyectó Necrosulfonamida a ratas (10 mg/kg) y se redujeron los niveles de receptor NOD-like 3 (NLRP3), GSDMD-N, MLKL fosforilado y RIP3 fosforilado en tejido cardíaco con una disminución correspondiente en los niveles de citocinas inflamatorias[5]. En vivo, se inyectó Necrosulfonamida a ratones (1, 5 o 10 mg/kg intraperitonealmente) mejorando la función motora y el edema espinal de ratones con SCI-Mice con una ventana terapéutica[6]. En vivo, se administró Necrosulfonamida a ratas (0.5 mg/cuerpo intraperitonealmente) protegiendo IRI pulmonar mediante la inhibición de necroptosis[7]. Se trató a ratones con NSA (0.5 mg/kg/día durante 3 días y 1mg/kg/día durante 7 días cada segundo día por inyección i.p.) restaurando defectos en el rendimiento motor, deficiencia de fibras TH+ estriatales y pérdida celular TH+ en un modelo murino de PD[8]. En vivo, se administró Necrosulfonamida a ratas (1.65 mg/kg/día intraperitonealmente durante 6 semanas) mejorando notablemente los déficits espaciales de aprendizaje y memoria inducidos por AlCl3, como lo demuestra el mejor rendimiento de las ratas en los laberintos acuáticos Morris y Y[9].

References:
[1] Zhang X, et al. Necrosulfonamide Alleviates Acute Brain Injury of Intracerebral Hemorrhage via Inhibiting Inflammation and Necroptosis. Front Mol Neurosci. 2022 Jun 2;15:916249.
[2] Teng JF, et al. Polyphyllin VI Induces Caspase-1-Mediated Pyroptosis via the Induction of ROS/NF-κB/NLRP3/GSDMD Signal Axis in Non-Small Cell Lung Cancer. Cancers (Basel). 2020 Jan 13;12(1):193.
[3] RÜbbelke M, et al. Locking mixed-lineage kinase domain-like protein in its auto-inhibited state prevents necroptosis. Proc Natl Acad Sci U S A. 2020 Dec 29;117(52):33272-33281.
[4] Rathkey JK, et al. Chemical disruption of the pyroptotic pore-forming protein gasdermin D inhibits inflammatory cell death and sepsis. Sci Immunol. 2018 Aug 24;3(26):eaat2738.
[5] He F, et al. Necrosulfonamide improves post-resuscitation myocardial dysfunction via inhibiting pyroptosis and necroptosis in a rat model of cardiac arrest. Eur J Pharmacol. 2022 Jul 5;926:175037.
[6] Jiao J, et al. Necrosulfonamide Ameliorates Neurological Impairment in Spinal Cord Injury by Improving Antioxidative Capacity. Front Pharmacol. 2020 Jan 9;10:1538.
[7] Ueda S, et al. Protective effect of necrosulfonamide on rat pulmonary ischemia-reperfusion injury via inhibition of necroptosis. J Thorac Cardiovasc Surg. 2022 Feb;163(2):e113-e122.
[8] Leem YH, et al. Necrosulfonamide exerts neuroprotective effect by inhibiting necroptosis, neuroinflammation, and α-synuclein oligomerization in a subacute MPTP mouse model of Parkinson's disease. Sci Rep. 2023 May 31;13(1):8783.
[9] Motawi TMK, et al. Ameliorative Effect of Necrosulfonamide in a Rat Model of Alzheimer's Disease: Targeting Mixed Lineage Kinase Domain-like Protein-Mediated Necroptosis. ACS Chem Neurosci. 2020 Oct 21;11(20):3386-3397.

Chemical Properties

Cas No. 1360614-48-7 SDF
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 Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

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1 mg 5 mg 10 mg
1 mM 2.167 mL 10.8349 mL 21.6699 mL
5 mM 0.4334 mL 2.167 mL 4.334 mL
10 mM 0.2167 mL 1.0835 mL 2.167 mL
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Average Rating: 5 ★★★★★ (Based on Reviews and 23 reference(s) in Google Scholar.)

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