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Inhibits necroptosis
Necrostatin-1 inhibits necroptosis, a non-apoptotic cell death pathway. Inhibits the loss of mitochondrial membrane potential in TNFα-treated Jurkat cells (EC50=490 nM). Does not inhibit FAS-induced apoptosis and has no effect on apoptotic morphology. It displays a pronounced protective effect in a mouse model of ischemic brain injury and inhibits myocardial cell death. Inhibits RIP1 kinase the key upstream kinase involved in the activation of necroptosis (EC50=180nM).
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Product Details
| Alternative Name |
Methylthiohydantoin-DL-tryptophan |
|---|---|
| Appearance |
Yellow solid. |
| CAS |
4311-88-0 |
| Couple Target |
RIP |
| Couple Type |
Inhibitor |
| Formula |
C13H13N3OS |
| MW |
259.3 |
| Purity |
≥98% (TLC) |
| Solubility |
Soluble in DMSO (20mg/ml) or 100% ethanol (5mg/ml). |
Handling & Storage
| Use/Stability |
As indicated on product label or CoA when stored as recommended. Stock solutions are stable for up to 3 months when stored at -20°C. |
|---|---|
| Handling |
Protect from light. |
| Long Term Storage |
Ambient |
| Shipping |
Ambient Temperature |
| Regulatory Status |
RUO – Research Use Only |
|---|
- Induction of Paraptotic Cell Death in Cancer Cells by Triptycene-Peptide Hybrids and the Revised Mechanism of Paraptosis II: M. Nii, et al.; Biochemistry 63, 2111 (2024), Abstract
- Neuronal autosis is Na+/K+-ATPase alpha 3-dependent and involved in hypoxic-ischemic neuronal death: Depierre, P., Ginet, V., et al.; Cell Death Dis. 15, 363 (2024), Abstract
- Integrated chemical and genetic screens unveil FSP1 mechanisms of ferroptosis regulation: T. Nakamura, et al.; Nat. Struct. Mol. Biol. 30, 1806 (2023), Abstract
- PRMT5-mediated regulatory arginine methylation of RIPK3: Chauhan, C., Martinez-Val, A., et al.; Cell Death Discov. 9, 14 (2023), Abstract
- 5-Iodotubercidin sensitizes cells to RIPK1-dependent necroptosis by interfering with NFκB signaling: Chauhan, C., Kraemer, A., et al.; Cell Death Discov. 9, 262 (2023), Abstract
- Triggering endogenous Z-RNA sensing for anti-tumor therapy through ZBP1-dependent necroptosis: T. Yang, et al.; Cell Rep. 42, 113377 (2023), Abstract
- Comparative mechanistic study of RPE cell death induced by different oxidative stresses: Tong, Y., Wu, Y., et al.; Redox Biol. 65, 102840 (2023), Abstract
- ROS-mediated activation of p38 protects hepatocellular carcinoma cells from caspase-independent death elicited by lysosomal damage: S. Castelli, et al.; Biochem. Pharmacol. 198, 114983 (2022), Abstract
- Lysosome‑targeted drug combination induces multiple organelle dysfunctions and non‑canonical death in pancreatic cancer cells: S. Suzuki, et al.; Oncol. Rep. 47, 40 (2022), Abstract
- TRAIL receptors promote constitutive and inducible IL-8 secretion in non-small cell lung carcinoma: F. Favaro, et al.; Cell Death Dis. 13, 1046 (2022), Abstract
- Catecholamine Surges Cause Cardiomyocyte Necroptosis via a RIPK1-RIPK3-Dependent Pathway in Mice: Wu, P., Cai, M., et al.; Front. Cardiovasc. Med. 8, 740839 (2021), Abstract
- RIP1 kinase inactivation protects against acetaminophen-induced acute liver injury in mice: Y. Yi, et al.; Free Radic. Biol. Med. 174, 57 (2021), Abstract
- Induction of synergistic non‑apoptotic cell death by simultaneously targeting proteasomes with bortezomib and histone deacetylase 6 with ricolinostat in head and neck tumor cells: K. Hattori, et al.; Oncol. Lett. 22, 680 (2021), Abstract
- Elesclomol-induced increase of mitochondrial reactive oxygen species impairs glioblastoma stem-like cell survival and tumor growth: M. Buccarelli, et al.; J. Exp. Clin. Cancer Res. 40, 228 (2021), Abstract
- TNF-induced necroptosis initiates early autophagy events via RIPK3-dependent AMPK activation, but inhibits late autophagy: W. Wu, et al.; Autophagy 17, 3992 (2021), Abstract
- HMGB1-associated necroptosis and Kupffer cells M1 polarization underlies remote liver injury induced by intestinal ischemia/reperfusion in rats: Wen, S., Li, X., et al.; FASEB J. 34, 4384 (2020), Abstract
- Molecular bases for HOIPINs-mediated inhibition of LUBAC and innate immune responses: D. Oikawa, et al.; Commun. Biol. 3, 163 (2020), Abstract — Full Text
- Autophagic death of neural stem cells mediates chronic stress-induced decline of adult hippocampal neurogenesis and cognitive deficits: Jung, S., Choe, S., et al.; Autophagy 16, 512 (2020), Abstract
- Beclin 1 Functions as a Negative Modulator of MLKL Oligomerisation by Integrating Into the Necrosome Complex: J. Seo, et al.; Cell Death Differ. 27, 3065 (2020), Abstract — Full Text
- Docosahexaenoic Acid Protection Against Palmitic Acid-Induced Lipotoxicity in NGF Differentiated PC12 Cells Involves Enhancement of Autophagy and Inhibition of Apoptosis and Necroptosis: M.L. Montero, et al.; J. Neurochem. 155, 559 (2020), Abstract — Full Text
- Caspase-8, receptor-interacting protein kinase 1 (RIPK1), and RIPK3 regulate retinoic acid-induced cell differentiation and necroptosis: M. Someda, et al.; Cell Death Differ. 27, 1539 (2020), Abstract — Full Text
- Kinase-Based Screening of Marine Natural Extracts Leads to the Identification of a Cytotoxic High Molecular Weight Metabolite from the Mediterranean Sponge Crambe tailliezi: T.N. Nguyen, et al.; Mar. Drugs 17, 569 (2019), Abstract — Full Text
- Ferroptosis in Neurons and Cancer Cells Is Similar But Differentially Regulated by Histone Deacetylase Inhibitors: M. Zille, et al.; eNeuro 6, ENEURO.0263-18.2019 (2019), Abstract — Full Text
- Ubiquitination of RIPK1 suppresses programmed cell death by regulating RIPK1 kinase activation during embryogenesis: X. Zhang, et al.; Nat. Commun. 10, 4158 (2019), Abstract — Full Text
- Cathepsin G inhibition by serpinb1 and serpinb6 prevents programmed necrosis in neutrophils and monocytes and reduces GSDMD-driven inflammation: S.S. Burgener, et al.; Cell Rep. 27, 3646 (2019), Abstract
- Autophagy regulates inflammatory programmed cell death via turnover of RHIM-domain proteins: Lim, J., Park, H., et al.; Elife 8, (2019), Abstract
- Targeting intestinal epithelial cell-programmed necrosis alleviates tissue injury after intestinal ischemia/reperfusion in rats: Li, X., Ling, Y., et al.; J. Surg. Res. 225, 108 (2018), Abstract
- Embryonic Lethality and Host Immunity of RelA-Deficient Mice Are Mediated by Both Apoptosis and Necroptosis: Xu, C., Wu, X., et al.; J. Immunol. 200, 271 (2018), Abstract
- Exploiting mitochondrial and metabolic homeostasis as a vulnerability in NF1 deficient cells: Allaway, R. J., Wood, M. D., et al.; Oncotarget 9, 15860 (2018), Abstract
- Cylindromatosis mediates neuronal cell death in vitro and in vivo: G.K. Ganjam, et al.; Cell Death Differ. 25, 1394 (2018), Abstract — Full Text
- The anti-myeloma activity of bone morphogenetic protein 2 predominantly relies on the induction of growth arrest and is apoptosis-independent: C. Lagler, et al.; PLoS One 12, e0185720 (2017), Application(s): Jurkat A3 cells, Abstract — Full Text
- Suberoylanilide hydroxamic acid increases anti-cancer effect of tumor necrosis factor-α through up-regulation of TNF receptor 1 in lung cancer cells: You, B. R., Han, B. R., et al.; Oncotarget 8, 17726 (2017), Abstract
- Cold-inducible RNA-binding protein through TLR4 signaling induces mitochondrial DNA fragmentation and regulates macrophage cell death after trauma: Z. Li, et al.; Cell Death Dis. 8, e2775 (2017), Abstract — Full Text
- Glucose Deprivation Induces ATF4-Mediated Apoptosis through TRAIL Death Receptors: R. Iurlaro, et al.; Mol. Cell. Biol. 37, e00479-16 (2017), Abstract — Full Text
- Caspase-3 Deletion Promotes Necrosis in Atherosclerotic Plaques of ApoE Knockout Mice: M.O. Grootaert, et al.; Oxid. Med. Cell Longev. 2016, 3087 (2016), Application(s): PI labeling experiements, Abstract — Full Text
- Inhibition of caspases primes colon cancer cells for 5-fluorouracil-induced TNF-α-dependent necroptosis driven by RIP1 kinase and NF-κB: M. Oliver Metzig, et al.; Oncogene 35, 3399 (2016), Application(s): Cell culture , Abstract
- Retinal pigment epithelial cell necroptosis in response to sodium iodate: J. Hanus, et al.; Cell Death Discov. 2, 16054 (2016), Application(s): Cell culture, transfection, treatments, and MTT assay (human cells), Abstract — Full Text
- MLKL and FADD Are Critical for Suppressing Progressive Lymphoproliferative Disease and Activating the NLRP3 Inflammasome: X. Zhang, et al.; Cell Rep. 16, 3247 (2016), Application(s): Necroptosis inhibition in WT mouse dermal fibroblasts, Abstract
- Auranofin induces mesothelioma cell death through oxidative stress and GSH depletion: You, B. R., Park, W. H., et al.; Oncol. Rep. 35, 546 (2016), Abstract
- Simultaneous induction of apoptosis and necroptosis by Tanshinone IIA in human hepatocellular carcinoma HepG2 cells: C.Y. Lin, et al.; Cell Death Discov. 2, 16065 (2016), Application(s): Cell viability assay, flow cytometry, cytotoxicity assay, immunoprecipitation and western blot; with human hepatoma cell line HepG2, Abstract — Full Text
- The Autophagy Machinery Controls Cell Death Switching between Apoptosis and Necroptosis: M.L. Goodall, et al.; Dev. Cell 37, 337 (2016), Abstract — Full Text
- Molecular features of the cytotoxicity of an NHE inhibitor: Evidence of mitochondrial alterations, ROS overproduction and DNA damage: F. Aredia, et al.; BMC Cancer 16, 851 (2016), Application(s): Colon carcinoma HCT-116 cells , Abstract — Full Text
- Macrolide Antibiotics Exhibit Cytotoxic Effect under Amino Acid-Depleted Culture Condition by Blocking Autophagy Flux in Head and Neck Squamous Cell Carcinoma Cell Lines: K. Hirasawa, et al.; PLoS One 11, e0164529 (2016), Abstract — Full Text
- Macrolides sensitize EGFR-TKI-induced non-apoptotic cell death via blocking autophagy flux in pancreatic cancer cell lines: Mukai, S., Moriya, S., et al.; Int. J. Oncol. 48, 45 (2016), Abstract
- The Different Effects of Atorvastatin and Pravastatin on Cell Death and PARP Activity in Pancreatic NIT-1 Cells: Y.H. Chen, et al.; J. Diabetes Res. 2016, 1828071 (2016), Abstract
- Retinal Cell Death Caused by Sodium Iodate Involves Multiple Caspase-Dependent and Caspase-Independent Cell-Death Pathways: Balmer, J., Zulliger, R., et al.; Int. J. Mol. Sci. 16, 15086 (2015), Abstract
- Toxin-Induced Necroptosis Is a Major Mechanism of Staphylococcus aureus Lung Damage: K. Kitur, et al.; PLoS Pathog. 11, e1004820 (2015), Application(s): Cell Culture, Abstract — Full Text
- Oxaliplatin triggers necrosis as well as apoptosis in gastric cancer SGC-7901 cells: P. Wu, et al.; Biochem. Biophys. Res. Commun. 460, 183 (2015), Application(s): Cell Culture, Abstract
- Differential roles of RIPK1 and RIPK3 in TNF-induced necroptosis and chemotherapeutic agent-induced cell death: K. Moriwaki, et al.; Cell Death Dis. 6, e1636 (2015), Application(s): Cell Culture, Abstract — Full Text
- ZFP36 stabilizes RIP1 via degradation of XIAP and cIAP2 thereby promoting ripoptosome assembly: T. Selmi, et al.; BMC Cancer 15, 357 (2015), Application(s): Cell Culture, Abstract — Full Text
- Modulation of P2X4/P2X7/Pannexin-1 sensitivity to extracellular ATP via Ivermectin induces a non-apoptotic and inflammatory form of cancer cell death: D. Draganov, et al.; Sci. Rep. 5, 16222 (2015), Abstract — Full Text
- A receptor-interacting protein 1 (RIP1)-independent necrotic death under the control of protein phosphatase PP2A that involves the reorganization of actin cytoskeleton and the action of cofilin-1: Tomasella, A., Blangy, A., et al.; J. Biol. Chem. 289, 25699 (2014), Abstract
- Betulinic acid-induced mitochrondria-dependent cell death is counter balanced by an autophagic salvage: L. Potze, et al.; Cell Death Dis. 5, e1169 (2014), Abstract — Full Text
- A novel role for the apoptosis inhibitor ARC in suppressing TNFα-induced regulated necrosis: G. Kung, et al.; Cell Death Differ. 21, 634 (2014), Abstract
- TRAF2 inhibits TRAIL- and CD95L-induced apoptosis and necroptosis: I. Karl, et al.; Cell Death Dis. 5, e1444 (2014), Abstract — Full Text
- Induction of necrotic cell death by oxidative stress in retinal pigment epithelial cells: Hanus, J., Zhang, H., et al.; Cell Death Dis. 4, e965 (2013), Abstract
- Plk1 is upregulated in androgen-insensitive prostate cancer cells and its inhibition leads to necroptosis: Deeraksa, A., Pan, J., et al.; Oncogene 32, 2973 (2013), Abstract
- The Isopeptidase Inhibitor G5 Triggers a Caspase-independent Necrotic Death in Cells Resistant to Apoptosis: A COMPARATIVE STUDY WITH THE PROTEASOME INHIBITOR BORTEZOMIB: A. Fontanini et al.; J. Biol. Chem. 284, 8369 (2009), Abstract
- Identification of RIP1 kinase as a specific cellular target of necrostatins: A. Degterev, et al.; Nat. Chem. Biol. 4, 313 (2008), Abstract
- Clinical aspects of indoleamine 2,3-dioxygenase (IDO)-initiated tryptophan metabolism: IDO is a target of drug discovery for various diseasea: O. Takikawa; Int. Congr. Ser. 1304, 290 (2007)
- Necrostatin: a potentially novel cardioprotective agent?: C.C. Smith et al.; Cardiovasc. Drugs Ther. 21, 227 (2007), Abstract
- Necrostatin-1 protects against glutamate-induced glutathione depletion and caspase-independent cell death in HT-22 cells: X. Xu et al.; J. Neurochem. 103, 2004 (2007), Abstract
- Chemical genetic approaches to probing cell death: B.R. Stockwell & N.M. Gangadhar; Curr. Opin. Chem. Biol. 11, 83 (2007), Abstract
- Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury: A. Degterev, et al.; Nat. Chem. Biol. 1, 112 (2005), Abstract
- Inhibition of indoleamine 2,3-dioxygenase, an immunoregulatory target of the cancer suppression gene Bin1, potentiates cancer chemotherapy: A.J. Muller et al.; Nat. Med. 11, 312 (2005), Abstract
Related Products
| Alternative Name | Nec-5, 3-p-Methoxyphenyl-5,6-tetramethylenothieno[2,3-d]pyrimidin-4-one-2-mercaptoethylcyanide |
|---|---|
| CAS | 337349-54-9 |
| Couple Type | Inhibitor |
| Purity | ≥98% (HPLC, TLC) |
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