| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg | |||
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| Targets |
Necrostatin 2 S enantiomer specifically targets receptor-interacting protein kinase 1 (RIPK1), a key regulator of necroptosis. It inhibits RIPK1 autophosphorylation in a dose-dependent manner. The compound lacks the IDO-targeting effect seen with some other necroptosis inhibitors, making it more selective for RIPK1. It also targets TNF-alpha, a cytokine involved in inflammation and cell death processes. The compound's mechanism involves blocking the RIPK1-dependent necroptosis pathway, thereby preventing TNF-alpha-induced cell death in appropriate cellular contexts.
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| ln Vitro |
In vitro studies have demonstrated that Necrostatin 2 S enantiomer is a potent inhibitor of necroptosis with an EC50 of 50 nM. The compound inhibits human recombinant RIPK1 with an IC50 of 320.0 nM. In FADD-deficient Jurkat cells treated with TNF-alpha, the compound exhibits an EC50 of 50 nM for inhibition of necroptosis. It shows low potency against human recombinant AurKA and AurKB with IC50 values greater than 3000 nM. The compound's selectivity for RIPK1 over other kinases makes it a valuable tool for studying necroptosis pathways.
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| ln Vivo |
In vivo studies have shown that Necrostatin 2 S enantiomer is efficacious in an animal model of ischemic stroke. The compound has been evaluated in various preclinical models of cell death and inflammation. It inhibits RIPK1-dependent necroptosis in vivo, demonstrating neuroprotective effects in ischemic injury models. The compound's efficacy in animal models supports its use as a research tool for studying necroptosis-related pathologies, including neurodegenerative diseases, inflammatory disorders, and ischemia-reperfusion injury. Detailed dose-response and pharmacokinetic studies have been conducted in rodents.
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| Enzyme Assay |
The in vitro enzyme/receptor binding assay for Necrostatin 2 S enantiomer typically involves kinase activity assays using purified recombinant RIPK1 protein. The compound is incubated with RIPK1 and a suitable peptide substrate in the presence of ATP. Kinase activity is measured by detecting phosphorylated substrate using methods such as radioactivity, fluorescence, or ELISA. IC50 values are determined from dose-response curves. Selectivity profiling is performed using panels of kinases including AurKA and AurKB. Data analysis using nonlinear regression models yields inhibition constants and confirms target engagement.
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| Cell Assay |
In vitro cellular assays for Necrostatin 2 S enantiomer are conducted using cell lines such as FADD-deficient Jurkat T cells. Cells are treated with TNF-alpha to induce necroptosis, and varying concentrations of the compound are added to assess inhibition. Cell death is measured using viability assays such as propidium iodide staining, LDH release, or MTT assays. The EC50 for inhibition of necroptosis is determined from dose-response curves. Control experiments include treatment with necroptosis inhibitors and assessment of apoptosis markers to confirm the specific inhibition of necroptosis rather than other cell death pathways.
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| Animal Protocol |
In vivo animal studies for Necrostatin 2 S enantiomer are typically performed in rodent models of ischemic stroke or other necroptosis-related pathologies. The compound is administered via intraperitoneal injection or other suitable routes at various doses. Efficacy is assessed by measuring infarct volume, neurological function scores, and survival rates. Tissue samples are collected for histopathological analysis and biomarker assessment. Pharmacodynamic markers such as RIPK1 phosphorylation are measured to confirm target engagement. Standard animal study designs with appropriate control groups are employed.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for Necrostatin 2 S enantiomer are limited in the available literature. The compound has a molecular weight of 277.71 g/mol and is formulated for research applications. As a small molecule inhibitor, it is expected to have reasonable oral bioavailability and tissue distribution. Pharmacokinetic studies in animal models have been conducted to support in vivo efficacy studies. The compound's metabolic stability, half-life, and clearance parameters would be determined using standard LC-MS/MS methods. However, specific PK parameters are not extensively reported in the public domain.
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| Toxicity/Toxicokinetics |
Toxicology data for Necrostatin 2 S enantiomer are not extensively reported. As a research compound, standard safety assessments would include evaluation of cytotoxicity in cell culture models and acute toxicity in animal studies. The compound's mechanism of action involving RIPK1 inhibition suggests potential effects on immune function and inflammation that would need to be evaluated. However, specific toxicity data, including LD50 values, organ toxicity profiles, and genotoxicity assessments, are not readily available. Standard preclinical safety evaluations would be required for therapeutic development.
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| References |
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| Additional Infomation |
Necrostatin 2 S enantiomer (Nec-1s) is the S-enantiomer of Necrostatin 2 and a potent necroptosis inhibitor with an EC50 of 50 nM. It acts as a RIPK1 inhibitor lacking the IDO-targeting effect and has demonstrated efficacy in an animal model of ischemic stroke. The compound has a molecular formula of C13H12ClN3O2. It is used as a research tool for studying necroptosis, inflammation, and cell death pathways. The compound is for research use only and is not approved for therapeutic applications.
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| Molecular Formula |
C13H12CLN3O2
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|---|---|
| Molecular Weight |
277.706281661987
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| Exact Mass |
277.062
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| CAS # |
852391-20-9
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| Related CAS # |
Necrostatin 2;852391-19-6;Necrostatin 2 racemate;852391-15-2
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| PubChem CID |
44404825
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| Appearance |
White to light yellow solid powder
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| LogP |
2.18
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
19
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| Complexity |
403
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CN1C(=O)[C@@H](NC1=O)CC2=CNC3=C2C=CC=C3Cl
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| InChi Key |
WIKGAEMMNQTUGL-JTQLQIEISA-N
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| InChi Code |
InChI=1S/C13H12ClN3O2/c1-17-12(18)10(16-13(17)19)5-7-6-15-11-8(7)3-2-4-9(11)14/h2-4,6,10,15H,5H2,1H3,(H,16,19)/t10-/m0/s1
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| Chemical Name |
(5S)-5-[(7-chloro-1H-indol-3-yl)methyl]-3-methylimidazolidine-2,4-dione
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| Synonyms |
Necrostatin 2 S enantiomer
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ~50 mg/mL (~180.0 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3 mg/mL (10.80 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 30.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 3 mg/mL (10.80 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 30.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 3 mg/mL (10.80 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.6009 mL | 18.0044 mL | 36.0088 mL | |
| 5 mM | 0.7202 mL | 3.6009 mL | 7.2018 mL | |
| 10 mM | 0.3601 mL | 1.8004 mL | 3.6009 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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