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Necrostatin-1RIP1 inhibitor


Catalog No. A4213
Size Price Stock Qty
10mg $60.00 In stock
100mg $170.00 In stock

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Sample solution is provided at 25 µL, 10mM.

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Biological Activity

Description Necrostatin-1 is a specific inhibitor of RIP1 and inhibits TNF-α-induced necroptosis with an EC50 value of 490 nM.
Targets RIP1          
IC50 490 nM (EC50)          

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Chemical Properties

Cas No. 4311-88-0 SDF Download SDF
Synonyms MTH-DL-Tryptophan,Nec-1
Chemical Name 5-(1H-indol-3-ylmethyl)-3-methyl-2-sulfanylideneimidazolidin-4-one
Canonical SMILES CN1C(=O)C(NC1=S)CC2=CNC3=CC=CC=C32
Formula C13H13N3OS M.Wt 259.33
Solubility Soluble in DMSO > 10 mM 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


IC50: Necrostatin-1 (Nec-1), (R)-5-([7-chloro-1H-indol-3-yl]methyl)-3-methylimidazolidine-2,4-dione (Nec-1a) (Figure 1A) (Degterev et al., 2008), exhibited an inhibitory constant (IC50) of 0.32 mM for RIP1 [1].
Necroptosis is a cellular mechanism of necrotic cell death induced by apoptotic stimuli in the form of death domain receptor engagement by their respective ligands under conditions where apoptotic execution is prevented. Necrostatin-1, identified as a small-molecule inhibitor of necroptosis, is also a selective allosteric inhibitor of the death domain receptor–associated adaptor kinase RIP1.
In vitro: Previous study indicated that necrostatin-1 was a selective allosteric inhibitor of the death domain receptor–associated adaptor kinase RIP1 in vitro. In this study, RIP1 was found to be the primary cellular target responsible for the antinecroptosis activity of necrostatin-1. In addition, two other necrostatins, necrostatin-3 and necrostatin-5, were also shown to target the RIP1 kinase step in the necroptosis pathway, but through different mechanism compared with that of necrostatin-1. The findings established necrostatins as the first-in-class inhibitors of RIP1 kinase, the key upstream kinase involved in the activation of necroptosis [2].
In vivo: A previous study was designed to investigate the protective effects and mechanisms of Nec-1 in concanavalin A-induced hepatitis in mice. It was found that in Nec-1-treated mice the amelioration in liver functions and histopathological changes and the suppression of inflammatory cytokine production were observed. Western blotting analyses showed that the expression of TNF-α, IFN-γ, IL2, IL6, and RIP1 was significantly reduced in the Nec-1-treated mice, which was further confirmed by immunofluorescence and immunohistochemistry. In addition, autophagosome formation was significantly reduced by Nec-1 treatment. These results indicated that Nec-1 could prevent concanavalin A -induced liver injury via RIP1-related and autophagy-related pathways [3].
Clinical trial: Up to now, Necroptosis is still in the preclinical development stage.
[1] Xie T, Peng W, Liu Y, Yan C, Maki J, Degterev A, Yuan J, Shi Y. Structural basis of RIP1 inhibition by necrostatins. Structure. 2013;21(3):493-9.
[2] Degterev A, Hitomi J, Germscheid M, Ch'en IL, Korkina O, Teng X, Abbott D, Cuny GD, Yuan C, Wagner G, Hedrick SM, Gerber SA, Lugovskoy A, Yuan J. Identification of RIP1 kinase as a specific cellular target of necrostatins. Nat Chem Biol. 2008;4(5):313-21.
[3] Yingqun Zhou, Weiqi Dai, Chunlei Lin, Fan Wang, Lei He, Miao Shen, Ping Chen, Chenfen Wang, Jie Lu, Ling Xu, Xuanfu Xu, and Chuanyong Guo. Protective Effects of Necrostatin-1 against Concanavalin A-Induced Acute Hepatic Injury in Mice. Mediators of Inflammation.