Usage
Necroptosis is a regulated caspase-independent cell death mechanism that results in morphological features resembling necrosis. Necrostatin-1 is an inhibitor of RIP1 kinase that prevents the death of
TNF-α-treated FADD-deficient Jurkat cells. Necrostatin-1 has been used to investigate the pathological importance of necroptosis in ischemic brain injury and myocardial infarction.
Usage
Necrostatin-1 is a specific RIP1 inhibitor and inhibits TNF-α-induced necroptosis with EC50 of 490 nM.
Biological Activity
ATP-competitive death domain receptor-associated adaptor kinase (RIP1) allosteric inhibitor (EC 50 = 182 nM). Blocks non-apoptotic cell death via inhibition of a specific cellular pathway, necroptosis, which leads to necrosis (EC 50 = 494 nM). Reduces ischemic brain injury in a mouse model of stroke.
Uses
Necroptosis is a regulated caspase-independent cell death mechanism that results in morphological features resembling necrosis. Necrostatin-1 is an inhibitor of RIP1 kinase that prevents the death of
TNF-α-treated FADD-deficient Jurkat cells. Necrostatin-1 has been used to investigate the pathological importance of necroptosis in ischemic brain injury and myocardial infarction.
Uses
Necroptosis is a regulated caspase-independent cell death mechanism that results in morphological features resembling necrosis. Necrostatin-1 is an inhibitor of RIP1 kinase that prevents the death of TNF-α-treated FADD-deficient Jurkat cells. Necrostatin-1 has been used to investigate the pathological importance of necroptosis in ischemic brain injury and myocardial infarction.
Uses
Necrostatin-1 is a specific RIP1 inhibitor and inhibits TNF-α-induced necroptosis with EC50 of 490 nM.
Definition
ChEBI: 5-(1H-indol-3-ylmethyl)-3-methyl-2-sulfanylidene-4-imidazolidinone is an organonitrogen compound and an organooxygen compound. It is functionally related to an alpha-amino acid.
Biochem/physiol Actions
Necrostatin-1(Nec-1) might exhibit therapeutic benefit against patients with traumatic brain injury (TBI). In addition, it might also be used to treat other acute central nervous system (CNS) disorders that feature necroptosis as a mode of cell death. It is extensively used to study the effect of receptor-interacting protein kinase 1 (RIPK1) on cell death and inflammation in experimental disease models. Nec‐1 protects hippocampal (HT‐22) cells from glutamate‐induced oxytosis via increasing cellular glutathione (GSH) levels, decreasing reactive oxygen species production, inhibiting the nuclear translocation of apoptosis‐inducing factor and B-cell lymphoma 2 (Bcl‐2) /adenovirus E1B 19kDa‐interacting protein 3‐related pathways.
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].
IC 50
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].
References
1) Degterev, et al. (2005), Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury‘ Nature Chem. Biol., 1 112
2) Degterev et al. (2008) Identification of RIP1 kinase as a specific cellular target of necrostatins; Nature Chem. Biol., 4 313
3) Smith et.al. (2007), Necrostatin: a potentially novel cardioprotective agent?; Cardiovasc. Drugs Ther., 21 227
4) Xu et.al. (2007), Necrostatin-1 protects against glutamate-induced glutathione depletion and caspase-independent cell death in HT-22 cells; J. Neurochem., 103 2004
