Necrosulfonamide | CAS#432531-71-0 | MLKL inhibitor

MedKoo Cat#: 525389 | Name: Necrosulfonamide

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Necrosulfonamide is a novel inhibitor of MLKL (mixed lineage kinase domain-like). Necrosulfonamide is a cell-permeable inhibitor that covalently modifies Cys88 and blocks human MLKL adaptor function. Necrosulfonamide Attenuates Spinal Cord Injury via Necroptosis Inhibition.

Chemical Structure

Necrosulfonamide

CAS#432531-71-0

Theoretical Analysis

MedKoo Cat#: 525389

Name: Necrosulfonamide

CAS#: 432531-71-0

Chemical Formula: C18H15N5O6S2

Exact Mass: 461.0464

Molecular Weight: 461.47

Elemental Analysis: C, 46.85; H, 3.28; N, 15.18; O, 20.80; S, 13.89

Price and Availability

Size	Price	Availability
10mg	USD 125.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 425.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,250.00	Ready to ship
500mg	USD 1,950.00	Ready to ship
1g	USD 2,950.00	Ready to ship
2g	USD 5,450.00	2 weeks

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Related CAS #

No Data

Synonym

Necrosulfonamide; MLKL inhibitor; Necrosis Inhibitor III; Mixed Lineage Kinase Domain-Like Protein Inhibitor; Necrosome Inhibitor II;

IUPAC/Chemical Name

N-(4-(N-(3-Methoxypyrazin-2-yl)sulfamoyl)phenyl)-3-(5-nitrothiophene-2-yl)acrylamide

InChi Key

FNPPHVLYVGMZMZ-XBXARRHUSA-N

InChi Code

InChI=1S/C18H15N5O6S2/c1-29-18-17(19-10-11-20-18)22-31(27,28)14-6-2-12(3-7-14)21-15(24)8-4-13-5-9-16(30-13)23(25)26/h2-11H,1H3,(H,19,22)(H,21,24)/b8-4+

SMILES Code

O=C(NC1=CC=C(S(=O)(NC2=NC=CN=C2OC)=O)C=C1)/C=C/C3=CC=C([N+]([O-])=O)S3

Appearance

Solid powder

Purity

>95% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in 1:50 DMF:PBS (pH 7.2); DMSO; DMF

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#A9T10K30

QC Data

View QC data: current batch, Lot#A9T10K30

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Necrosulfonamide is a necroptosis inhibitor acting by selectively targeting the mixed lineage kinase domain-like protein (MLKL).

In vitro activity:

Results showed that IL-1β significantly increased the caspase3/8, RIPK1, RIPK3, and MLKL compared with control group. After treatment of NSA (necrosulfonamide), all the expression of these proteins decreased compared with IL-1β group (Figure 3A). Also, this sequence was found in mRNA levels with RT-PCR method and flow cytometry analysis of apoptosis (Figure 3B, 3C). All these results indicated that the appropriate dose of NSA could inhibit the necroptosis and apoptosis of human NP cells, protecting the IVDD (intervertebral disc degeneration). Reference: Eur Rev Med Pharmacol Sci. 2020 Mar;24(5):2683-2691. https://pubmed.ncbi.nlm.nih.gov/32196619/

In vivo activity:

In NSA (necrosulfonamide)-treated mice (at 15 min, 1 h, 6 h, and 12 h after SCI (spinal cord injury)), p-MLKL expression was reduced after SCI; however, it was still high in the NSA-treated group at 24 h (p < 0.05, Figure 6A). SCI induced mitochondrial dysfunction at 3 days post-SCI, including the reduction of ATP, MMP, and the abnormal antioxidant capacity (Figures 6B–D). Treatment with NSA at 15 min, 1 h, 6 h, and 12 h after SCI significantly ameliorated the ATP and MMP levels (Figure 6B, p < 0.05, respectively). SCI led to an increase in ROS and MDA levels and a decrease in SOD and GSH levels compared to the sham group (Figures 6C, D, p < 0.05, respectively). NSA treatment (in 15 min, 1 h, 6 h, and 12 h groups) resulted in a significant reduction in ROS and MDA levels and an increase in SOD and GSH levels compared to the SCI group (Figures 6C, D, p < 0.05, respectively). The effect on MMP and SOD was weaker in the 24 h group than that in the other NSA groups, but the 24 h group still revealed significant improvement in the ATP, ROS, MDA, and GSH levels compared to the SCI + vehicle group (Figures 6B–D, p < 0.05, respectively). Therefore, NSA demonstrated a more superior effect on mitochondrial dysfunction, including improvements in mitochondrial integrity and antioxidant capacity, within 12 h after SCI compared to the treatment at 24 h. Reference: Front Pharmacol. 2019; 10: 1538. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6962303/

	Solvent	mg/mL	mM
Solubility
	DMSO	100.0	216.70

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 461.47 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Zhang QX, Guo D, Wang FC, Ding WY. Necrosulfonamide (NSA) protects intervertebral disc degeneration via necroptosis and apoptosis inhibition. Eur Rev Med Pharmacol Sci. 2020 Mar;24(5):2683-2691. doi: 10.26355/eurrev_202003_20538. PMID: 32196619. 2. Jiao J, Wang Y, Ren P, Sun S, Wu M. Necrosulfonamide Ameliorates Neurological Impairment in Spinal Cord Injury by Improving Antioxidative Capacity. Front Pharmacol. 2020 Jan 9;10:1538. doi: 10.3389/fphar.2019.01538. PMID: 31998134; PMCID: PMC6962303.

In vitro protocol:

In vivo protocol:

1. Jiao J, Wang Y, Ren P, Sun S, Wu M. Necrosulfonamide Ameliorates Neurological Impairment in Spinal Cord Injury by Improving Antioxidative Capacity. Front Pharmacol. 2020 Jan 9;10:1538. doi: 10.3389/fphar.2019.01538. PMID: 31998134; PMCID: PMC6962303.

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Key roles of necroptotic factors in promoting tumor growth. Oncotarget. 2016 Apr 19;7(16):22219-33. doi: 10.18632/oncotarget.7924. PubMed PMID: 26959742; PubMed Central PMCID: PMC5008357. 5: Mulay SR, Desai J, Kumar SV, Eberhard JN, Thomasova D, Romoli S, Grigorescu M, Kulkarni OP, Popper B, Vielhauer V, Zuchtriegel G, Reichel C, Bräsen JH, Romagnani P, Bilyy R, Munoz LE, Herrmann M, Liapis H, Krautwald S, Linkermann A, Anders HJ. Cytotoxicity of crystals involves RIPK3-MLKL-mediated necroptosis. Nat Commun. 2016 Jan 28;7:10274. doi: 10.1038/ncomms10274. PubMed PMID: 26817517; PubMed Central PMCID: PMC4738349. 6: Desai J, Kumar SV, Mulay SR, Konrad L, Romoli S, Schauer C, Herrmann M, Bilyy R, Müller S, Popper B, Nakazawa D, Weidenbusch M, Thomasova D, Krautwald S, Linkermann A, Anders HJ. PMA and crystal-induced neutrophil extracellular trap formation involves RIPK1-RIPK3-MLKL signaling. Eur J Immunol. 2016 Jan;46(1):223-9. doi: 10.1002/eji.201545605. Epub 2015 Nov 30. PubMed PMID: 26531064. 7: Qiu X, Klausen C, Cheng JC, Leung PC. CD40 ligand induces RIP1-dependent, necroptosis-like cell death in low-grade serous but not serous borderline ovarian tumor cells. Cell Death Dis. 2015 Aug 27;6:e1864. doi: 10.1038/cddis.2015.229. PubMed PMID: 26313915; PubMed Central PMCID: PMC4558516. 8: Skrzeczyńska-Moncznik J, Bzowska M, Nogieć A, Sroka A, Zarębski M, Vallières L, Guzik K. Rapid externalization of 27-kDa heat shock protein (HSP27) and atypical cell death in neutrophils treated with the sphingolipid analog drug FTY720. J Leukoc Biol. 2015 Oct;98(4):591-9. doi: 10.1189/jlb.3VMA1114-522RR. Epub 2015 Jul 27. PubMed PMID: 26216939. 9: Koo MJ, Rooney KT, Choi ME, Ryter SW, Choi AM, Moon JS. Impaired oxidative phosphorylation regulates necroptosis in human lung epithelial cells. Biochem Biophys Res Commun. 2015 Aug 28;464(3):875-80. doi: 10.1016/j.bbrc.2015.07.054. Epub 2015 Jul 14. PubMed PMID: 26187663. 10: Steinwascher S, Nugues AL, Schoeneberger H, Fulda S. Identification of a novel synergistic induction of cell death by Smac mimetic and HDAC inhibitors in acute myeloid leukemia cells. Cancer Lett. 2015 Sep 28;366(1):32-43. doi: 10.1016/j.canlet.2015.05.020. Epub 2015 May 28. PubMed PMID: 26028172. 11: Blohberger J, Kunz L, Einwang D, Berg U, Berg D, Ojeda SR, Dissen GA, Fröhlich T, Arnold GJ, Soreq H, Lara H, Mayerhofer A. Readthrough acetylcholinesterase (AChE-R) and regulated necrosis: pharmacological targets for the regulation of ovarian functions? Cell Death Dis. 2015 Mar 12;6:e1685. doi: 10.1038/cddis.2015.51. PubMed PMID: 25766324; PubMed Central PMCID: PMC4385929. 12: Melo-Lima S, Celeste Lopes M, Mollinedo F. Necroptosis is associated with low procaspase-8 and active RIPK1 and -3 in human glioma cells. Oncoscience. 2014 Oct 22;1(10):649-64. eCollection 2014. PubMed PMID: 25593994; PubMed Central PMCID: PMC4278276. 13: El-Mesery M, Seher A, Stühmer T, Siegmund D, Wajant H. MLN4924 sensitizes monocytes and maturing dendritic cells for TNF-dependent and -independent necroptosis. Br J Pharmacol. 2015 Mar;172(5):1222-36. doi: 10.1111/bph.12998. Epub 2015 Jan 13. PubMed PMID: 25363690; PubMed Central PMCID: PMC4337697. 14: Steinhart L, Belz K, Fulda S. Smac mimetic and demethylating agents synergistically trigger cell death in acute myeloid leukemia cells and overcome apoptosis resistance by inducing necroptosis. Cell Death Dis. 2013 Sep 12;4:e802. doi: 10.1038/cddis.2013.320. PubMed PMID: 24030154; PubMed Central PMCID: PMC3789178. 15: Dunai ZA, Imre G, Barna G, Korcsmaros T, Petak I, Bauer PI, Mihalik R. Staurosporine induces necroptotic cell death under caspase-compromised conditions in U937 cells. PLoS One. 2012;7(7):e41945. doi: 10.1371/journal.pone.0041945. Epub 2012 Jul 31. PubMed PMID: 22860037; PubMed Central PMCID: PMC3409216. 16: Sun L, Wang H, Wang Z, He S, Chen S, Liao D, Wang L, Yan J, Liu W, Lei X, Wang X. Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase. Cell. 2012 Jan 20;148(1-2):213-27. doi: 10.1016/j.cell.2011.11.031. PubMed PMID: 22265413.