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| 10mg |
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| 100mg |
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| Targets |
RIPK1
RIPK1 (receptor-interacting serine/threonine kinase 1). Necrostatin-34 inhibits RIPK1 kinase activity with an IC50 of 5.5 µM in biochemical assays. It stabilizes RIPK1 in an inactive conformation. In L929 cells, it has an IC50 of 0.13 µM for inhibiting TNF-α-induced necroptosis. |
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| ln Vitro |
Necrostatin-34 (Nec-34) in FADD def-Jurkat cells and L939 cells had IC50 values for TNFα of 667 nM and 134 nM, respectively[1]. The phosphorylation of RIPK1's Ser166 (p-S166), a biomarker for RIPK1 activation, indicates that necrostatin-34 (Nec-34, 10 μM) suppresses the dimerization-induced RIPK1 activation[1]. Necrostatin-34 (Nec-34) has the potential to prevent TNFα-induced complex II formation by impeding RIPK1 kinase activation[1].
Necrostatin-34 inhibits TNF-α-induced necroptosis in Jurkat cells lacking FADD and L-929 cells with IC50s of 6.67 and 1.35 µM, respectively. In L929 cells, it has an IC50 of 0.13 µM. It has IC50s of 667 nM and 134 nM for TNFα in FAD-deficient Jurkat cells and L929 cells, respectively. |
| ln Vivo |
In vivo activity data for Necrostatin-34 is not extensively detailed in standard references. As a RIPK1 kinase inhibitor, it is expected to show efficacy in animal models of necroptosis-related diseases, such as ischemia-reperfusion injury, inflammatory diseases, and neurodegenerative disorders.
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| Enzyme Assay |
In vitro kinase assays are performed using recombinant RIPK1 kinase and a peptide substrate. The phosphorylation reaction is monitored using a radioisotope or fluorescence-based method. The compound is incubated with the enzyme and substrate, and the inhibition of kinase activity is quantified.
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: RIPK1 knockout L929 cells transfected with an expressing vector encoding an inducible and dimerizable RIPK1 fused with FKBP at the C-terminus. Tested Concentrations: 10 μM. Incubation Duration: 30 min (and then 100 ng/mL TNFα was added for indicated periods of time). Experimental Results: Downregulated p-S166 levels. Cells (e.g., Jurkat or L-929) are treated with TNF-α and a caspase inhibitor (z-VAD-fmk) to induce necroptosis. Necrostatin-34 is added at various concentrations. Cell viability is measured using MTT, CellTiter-Glo, or propidium iodide staining. |
| Animal Protocol |
In vivo efficacy studies are performed in animal models of necroptosis. Necrostatin-34 is administered via intraperitoneal or intravenous routes. Disease endpoints (e.g., infarct size, inflammation scores, neurological deficits) are assessed. Tissues are collected for histopathological and biochemical analysis.
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| ADME/Pharmacokinetics |
Necrostatin-34 has a molecular weight of 384.48 and a molecular formula of C18H16N4O2S2. It is soluble in DMSO (≥100 mg/mL). It is stored at 2-8°C, protected from light, dry, and sealed. Detailed PK data is not available.
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| Toxicity/Toxicokinetics |
Detailed toxicological profiles of Necrostatin-34 are not extensively reported. As a research compound, it is expected to have a manageable safety profile at the concentrations used in cell-based assays. Cytotoxicity is assessed in parallel with anti-necroptotic activity to determine the selectivity index.
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| References | |
| Additional Infomation |
Necrostatin-34 is a research-grade RIPK1 kinase inhibitor. It is used as a tool to study necroptosis and its role in various diseases. It is not approved for clinical use. Its molecular formula is C18H16N4O2S2 and its molecular weight is 384.48.
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| Molecular Formula |
C18H16N4O2S2
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|---|---|
| Molecular Weight |
384.48
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| Exact Mass |
384.071
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| CAS # |
375835-43-1
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| PubChem CID |
3841655
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| Appearance |
Off-white to light yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Index of Refraction |
1.675
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| LogP |
0.968
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
26
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| Complexity |
634
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=CC=C(C=C1)C2CC(=O)NC(=C2C#N)SCC(=O)NC3=NC=CS3
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| InChi Key |
LOQIRQHGJVGIEL-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H16N4O2S2/c1-11-2-4-12(5-3-11)13-8-15(23)21-17(14(13)9-19)26-10-16(24)22-18-20-6-7-25-18/h2-7,13H,8,10H2,1H3,(H,21,23)(H,20,22,24)
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| Chemical Name |
2-[[5-cyano-4-(4-methylphenyl)-2-oxo-3,4-dihydro-1H-pyridin-6-yl]sulfanyl]-N-(1,3-thiazol-2-yl)acetamide
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 : 125 mg/mL (325.11 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.41 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 20.8 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: ≥ 2.08 mg/mL (5.41 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6009 mL | 13.0046 mL | 26.0092 mL | |
| 5 mM | 0.5202 mL | 2.6009 mL | 5.2018 mL | |
| 10 mM | 0.2601 mL | 1.3005 mL | 2.6009 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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