Necrostatin-1

SKU: orb1307335

Description

Necrostatin-1

Research Area

Cell Biology, Metabolism Research, Signal Transduction

Key Properties

• CAS Number: 4311-88-0
• MW: 259.33
• Purity: 99.57%
• Formula: C₁₃H₁₃N₃OS
• SMILES: CN1C(=S)NC(Cc2c[nH]c3ccccc23)C1=O
• Target: Indoleamine 2,3-Dioxygenase (IDO),Ferroptosis,RIP kinase,IDO,Autophagy
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:4 mg/mL (15.42 mM);DMSO:245 mg/mL (944.74 mM)

Bioactivity

• Target IC50:
  RIP1:490 nM (EC50, Jurkat cells)|RIP1:182 nM (EC50)|Jurkat cells:494 nM|Sf9 cells:182 nM
• In Vivo:
  METHODS: To stud the pathophysiology of contrast-induced AKI (CIAKI), Necrostatin-1 (1.65 mg/kg) was administered intraperitoneally as a Single injection to C57B-/- mice, and CIAKI was induced by using radiocontrast media (RCM) 15 min later. Results: Necrostatin-1 prevented osmotic nephropathy and CIAKI. Necrostatin-1 blocked RCM-induced peritubular capillary dilatation, suggesting tha the structural domain of RIP1 kinase has a novel role in regulatin the microvascular hemodynamics and pathophysiology of CIAKI that is independent of cell death. METHODS: To investigat the Protective effect and mechanism of hepatitis in mice, Necrostatin-1 (1.8 mg/kg) was administered intraperitoneally to C57B-/- mice as a Single injection, and concanavalin A was used to induce hepatitis 1 h later. Results: Improvements in liver function and histopathologic changes, as well as suppression of inflammatory cytokine production, were observed in Necrostatin-1-injected mice the expression of TNF-α, IFN-γ, IL2, IL6, and RIP1 was significantly reduced in Necrostatin-1-injected mice, and autophagosome formation was significantly reduced by Necrostatin-1 treatment the RESULTS suggest that Necrostatin-1 prevents concanavalin A-induced liver injury through RIP1-related and autophagy-related pathways.
• In Vitro:
  METHODS: Human hepatocellular carcinoma cells Huh7 and SK-HEP-1 were pretreated with Necrostatin-1 (10-20 µM) for 1 h, and then treated with sulfasalazine, erastin or RSL3 for 24 h. Cell viability was measured by CellTiter Glo® assay. Results: Necrostatin-1 significantly blocke the decrease in cell viability induced by sulfasalazine and erastin In both cell lines and partially reverse the decrease in cell viability induced by RSL3 in SK-HEP-1 cells. METHODS: Human histiocytic lymphoma cells U937 were treated with Necrostatin-1 (1-20 µM), zVAD.fmk (100 μM), and TNFα (10 ng/mL) for 72 h. Cell viability was detected by ATP-based viability assay. Results: Necrostatin-1 effectively blocke the necrotic death of U937 cells in a concentration dependent manner. METHODS: H/R injury-induced human renal papillomatous cells HK-2 were treated with Necrostatin-1 (30 mmol/L) for 2-12 h. Cell death was analyzed by Flow Cytometry. Results: Necrostatin-1 partially protected HK-2 cells from H/R-induced necrosis.
• Cell Research:
  Determination of EC50 was performed in FADD-deficient Jurkat cells treated with human TNFα as previously described. Briefly, cells were seeded into 96-well plates and treated with a range of necrostatin concentration (30 nM to 100 μM, 11 dose points) in the presence and absence of 10 ng ml–1 human TNFα for 24 h. For these and All Other cellular assays, compound stocks (in DMSO) were diluted to appropriate concentration in DMSO before addition to the cells to maintain final concentration of DMSO for All Samples at 0.5%. Cell viability was determined using CellTiter-Glo luminescent cell viability assay. Ratio of luminescence in compound and TNF-treated wells to compound-treated, TNF-untreated wells was calculated (viability, %).
• Animal Research:
  24 hours after reperfusion, mice received intravenous application of 200 μL PBS or RCM vi the tail vein. a single dose of zVAD (10 mg/kg body weight) or Nec-1 (1.65 mg/kg body weight) was applied intraperitoneally 15 min. before RCM-injection. To tes the activity of zVAD, we applied zVAD fro the same byculture to anti-Fas-treated Jurkat cells to assure its quality before mice were treated with this compound. Mice were Harvested a Other 24 hours after RCM-application (48 hours after reperfusion). Blood Samples were obtained from retroorbital bleeding and serum levels of urea and creatinine 5 were determined according to clinical s andards in the central laboratory o the University Hospital Schleswig-Holstein, Campus Kiel, Germany, employing an enzymatic ultraviolettest for urea and an enzymatic peroxidase-dependent test for creatinine according to the manufacturer's instructions. Kidneys were conserved for histology. In addition to the demonstrated experiments, we Compare the PBS group to mice that only received IRI without 200 μL of PBS and detected no Changes in serum concentration of urea and creatinine or histologically.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Disclaimer: For research use only

Alternative Names

Autophagy, Ferroptosis, IDO, inhibit, Inhibitor, Indoleamine 2,3-Dioxygenase, Indoleamine 2,3Dioxygenase (IDO), Indoleamine2,3Dioxygenase(IDO), Indoleamine2,3Dioxygenase, Indoleamine 2,3-Dioxygenase (IDO), Necrostatin 1, Necrostatin1, Necrostatin-1, Nec 1, Nec1, Nec-1, Receptor-interacting protein kinases, RIP kinase, RIPK, RIP1, RIPkinase

Compound Identifiers

PubChem CID

2828334