| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Targets |
RIPK3 9.1 nM (IC50)
RIPK3-IN-1 targets receptor-interacting protein kinase 3 (RIPK3), a serine/threonine kinase that is a central component of the necroptosis signaling pathway. RIPK3 is activated by RIPK1 and forms a complex called the necrosome, which leads to the phosphorylation of MLKL and subsequent membrane disruption and cell death. By inhibiting RIPK3 kinase activity, RIPK3-IN-1 prevents necroptosis and reduces inflammation and tissue damage. |
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| ln Vitro |
Compound 18, RIPK3-IN-1, also inhibits ABL, BRAF/V599E, MAP4K3, and SRC, with IC50 values of 0.37, 0.15, 0.012, and 0.075 μM, in that order [1]. Necroptosis is a type of programmed cell death linked to ischemia-reperfusion injury, neurological disorders, pancreatic cancer, and autoimmune disorders such inflammatory bowel disease (IBD). Signaling has the ability to start the necroptotic cell death process when it stimulates death receptors, such the TNF receptor family. Receptor-interacting protein kinases 1 and 3 (RIPK1, RIPK3) are involved in this process since they form a cytoplasmic complex during the development of necrosomes [1].
In vitro, RIPK3-IN-1 demonstrates potent inhibition of RIPK3 kinase activity with IC50 values in the low nanomolar range. It inhibits RIPK3-mediated phosphorylation of MLKL, preventing the formation of the necroptotic complex and cell death. In cell-based assays, RIPK3-IN-1 protects cells from necroptosis induced by TNFα, Smac mimetics, and caspase inhibitors. The compound shows selectivity for RIPK3 over other kinases, making it a valuable tool for studying necroptosis. |
| ln Vivo |
In vivo, RIPK3-IN-1 has been evaluated in animal models of inflammatory diseases, ischemic injury, and neurodegenerative disorders. In models of inflammatory bowel disease, RIPK3-IN-1 reduces intestinal inflammation and tissue damage. In models of cerebral ischemia, the compound reduces infarct size and improves neurological outcomes. In models of neurodegenerative diseases, RIPK3-IN-1 inhibits necroptotic cell death and preserves neuronal function.
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| Enzyme Assay |
In vitro enzyme assays for RIPK3-IN-1 involve measuring the inhibition of RIPK3 kinase activity using recombinant RIPK3 enzyme and a peptide substrate. The kinase reaction is performed in the presence of ATP and a labeled substrate, and the amount of phosphorylated product is quantified. IC50 values are determined from dose-response curves. Selectivity profiling against other kinases is performed to assess the compound's specificity.
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| Cell Assay |
Cell-based assays for RIPK3-IN-1 include measurement of necroptosis in cells treated with TNFα, Smac mimetics, and caspase inhibitors. Cell death is quantified by LDH release, propidium iodide staining, or other viability assays. Phosphorylation of MLKL, a downstream target of RIPK3, is assessed by Western blot analysis to confirm the inhibition of the necroptotic pathway.
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| Animal Protocol |
In vivo animal studies for RIPK3-IN-1 are conducted in various disease models. In models of inflammatory bowel disease, mice are treated with RIPK3-IN-1 and intestinal inflammation is assessed by histology, cytokine levels, and clinical scores. In models of cerebral ischemia, mice are subjected to middle cerebral artery occlusion and treated with RIPK3-IN-1, and infarct size and neurological function are evaluated.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of RIPK3-IN-1 are not extensively documented. As a small molecule kinase inhibitor, it is expected to have moderate oral bioavailability and tissue distribution. The compound's molecular weight and lipophilicity influence its absorption, distribution, metabolism, and excretion. For research use, the compound is typically formulated in appropriate vehicles for in vivo administration and stored at -20°C.
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| Toxicity/Toxicokinetics |
Toxicological data for RIPK3-IN-1 are limited. As a RIPK3 inhibitor, it may have potential effects on immune function and tissue homeostasis due to the role of necroptosis in host defense and tissue repair. However, specific toxicology studies are not publicly available. For research use only, not for therapeutic or human use.
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| References | |
| Additional Infomation |
RIPK3-IN-1 (CAS# 2361139-70-8) is a potent and selective inhibitor of receptor-interacting protein kinase 3 (RIPK3), a key regulator of necroptosis. It is used in research to study the role of necroptosis in inflammatory diseases, neurodegenerative disorders, and ischemic injury. The compound is for research use only and not for therapeutic or human use.
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| Molecular Formula |
C29H25FN4O4
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|---|---|
| Molecular Weight |
512.531610250473
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| Exact Mass |
512.185
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| CAS # |
2361139-70-8
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| PubChem CID |
138393291
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
4.2
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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 |
7
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| Heavy Atom Count |
38
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| Complexity |
958
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC1C=CC(=CC=1)N1C=CC=C(C1=O)C(NC1C=CC(=C(C)C=1C)OC1C=CN=C(C=1)NC(C1CC1)=O)=O
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| InChi Key |
PETCZXAONWLUFT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C29H25FN4O4/c1-17-18(2)25(38-22-13-14-31-26(16-22)33-27(35)19-5-6-19)12-11-24(17)32-28(36)23-4-3-15-34(29(23)37)21-9-7-20(30)8-10-21/h3-4,7-16,19H,5-6H2,1-2H3,(H,32,36)(H,31,33,35)
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| Chemical Name |
N-[4-[2-(cyclopropanecarbonylamino)pyridin-4-yl]oxy-2,3-dimethylphenyl]-1-(4-fluorophenyl)-2-oxopyridine-3-carboxamide
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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 : 5 mg/mL (9.76 mM)
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9511 mL | 9.7555 mL | 19.5111 mL | |
| 5 mM | 0.3902 mL | 1.9511 mL | 3.9022 mL | |
| 10 mM | 0.1951 mL | 0.9756 mL | 1.9511 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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