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| Targets |
RIPK2-IN-8 targets receptor-interacting protein kinase 2 (RIPK2), a serine/threonine kinase that plays a critical role in the innate immune response. RIPK2 is a key adaptor protein in the NOD1 and NOD2 signaling pathways, which are involved in the recognition of bacterial peptidoglycan fragments. Upon activation, NOD1/2 recruit RIPK2, which then undergoes autophosphorylation and activates downstream signaling cascades, including the NF-κB and MAPK pathways, leading to the production of pro-inflammatory cytokines. By inhibiting RIPK2 with an IC50 of 3 nM, RIPK2-IN-8 blocks these signaling pathways and reduces the production of inflammatory mediators. The compound's high selectivity for RIPK2 over other kinases minimizes off-target effects.
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| ln Vitro |
In vitro studies have demonstrated that RIPK2-IN-8 is a potent and selective inhibitor of RIPK2 kinase activity. It inhibits RIPK2 with an IC50 of 3 nM, as measured in kinase activity assays. In a broad panel of 250 kinases, 90% of kinases showed <50% inhibition, confirming the compound's high selectivity for RIPK2. In cell-based assays, RIPK2-IN-8 effectively suppresses IL-6 secretion in mouse bone marrow-derived macrophages with an IC50 of 12 nM. It also significantly reverses MDP-induced pro-inflammatory cytokines in rat colon explants. These findings establish RIPK2-IN-8 as a valuable tool for studying RIPK2-mediated inflammatory responses.
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| ln Vivo |
In vivo activity of RIPK2-IN-8 has been demonstrated in animal models. In a rat colon model, RIPK2-IN-8 significantly reverses MDP-induced pro-inflammatory cytokines, confirming its ability to inhibit RIPK2-mediated inflammation in vivo. The compound is orally available, making it suitable for oral administration in animal studies. However, specific details regarding the in vivo efficacy of RIPK2-IN-8, such as the dosing regimens and the animal models used, are not extensively detailed in the available literature. Its ability to suppress IL-6 secretion in macrophages in vitro suggests that it would have similar anti-inflammatory effects in vivo. RIPK2-IN-8 is used in research to study the role of RIPK2 in inflammatory diseases and to validate RIPK2 as a therapeutic target.
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| Enzyme Assay |
The in vitro enzyme assay for RIPK2-IN-8 measures its inhibition of RIPK2 kinase activity. In a typical assay, recombinant RIPK2 protein is incubated with a peptide substrate and ATP in the presence of varying concentrations of RIPK2-IN-8. The incorporation of phosphate into the substrate is measured using a radiometric (e.g., 33P-ATP) or fluorescent method. The inhibition of kinase activity is calculated, and the IC50 is determined from the dose-response curve. To confirm selectivity, the compound is tested against a panel of other kinases (e.g., 250 kinases). The percentage of inhibition at a single concentration or the IC50 for each kinase is determined to assess the selectivity profile. These assays provide a quantitative measure of RIPK2-IN-8's potency and selectivity at the molecular level.
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| Cell Assay |
In vitro cell-based assays for RIPK2-IN-8 are used to study its effects on RIPK2-mediated signaling and inflammatory responses. A common assay involves using mouse bone marrow-derived macrophages (BMDMs) or other immune cells. The cells are treated with a RIPK2 activator, such as muramyl dipeptide (MDP), a NOD2 agonist, in the presence or absence of RIPK2-IN-8. The production of pro-inflammatory cytokines, such as IL-6, TNF-α, and IL-1β, is measured in the culture supernatant by ELISA. The phosphorylation of downstream signaling molecules, such as NF-κB and MAPK, can also be assessed by Western blotting. These assays confirm that RIPK2-IN-8 inhibits RIPK2-mediated inflammatory responses in a cellular context.
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| Animal Protocol |
In vivo animal experiments for RIPK2-IN-8 are conducted to evaluate its anti-inflammatory efficacy. In a typical protocol, rats are treated with MDP to induce a RIPK2-mediated inflammatory response in the colon. RIPK2-IN-8 is administered orally, and the levels of pro-inflammatory cytokines in the colon tissue are measured. The compound's ability to reverse MDP-induced cytokine production is assessed. Other models of RIPK2-mediated inflammation, such as models of inflammatory bowel disease (IBD) or rheumatoid arthritis, could also be used to evaluate the compound's efficacy. However, specific protocols for RIPK2-IN-8 are not extensively detailed in the available literature. The compound's oral availability makes it a promising tool for in vivo studies.
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| ADME/Pharmacokinetics |
RIPK2-IN-8 has a molecular weight of 392.45 g/mol and a molecular formula of C18H21FN4O3S. It is a solid powder with a purity of >98%. RIPK2-IN-8 is soluble in DMSO at 31.25 mg/mL (79.63 mM). For storage, it is recommended to keep the powder at -20°C. The compound is stable for at least 2 years under recommended storage conditions. It is shipped with an ice pack to maintain stability during transit. Pharmacokinetic properties such as half-life, bioavailability, and tissue distribution have not been extensively detailed in the available literature, but the compound is reported to be orally available.
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| Toxicity/Toxicokinetics |
Detailed toxicity data for RIPK2-IN-8 is not provided in standard product descriptions. As a research compound, its toxicity profile has not been extensively characterized. In vitro studies have shown that the compound is selective for RIPK2 over a broad panel of kinases, suggesting that it may have a favorable off-target safety profile. However, comprehensive toxicological studies, including acute and chronic toxicity studies, have not been reported. As with all research chemicals, standard laboratory safety precautions should be followed when handling RIPK2-IN-8. Its use is limited to research applications and it is not intended for human or veterinary use.
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| References | |
| Additional Infomation |
RIPK2-IN-8 is a research compound and is not approved for any clinical or therapeutic use. It is a potent, selective, and orally available inhibitor of RIPK2, with an IC50 of 3 nM. RIPK2-IN-8 displays high selectivity, with 90% of kinases showing <50% inhibition in a broad 250-kinase panel. It effectively suppresses IL-6 secretion in mouse bone marrow-derived macrophages with an IC50 of 12 nM and significantly reverses MDP-induced pro-inflammatory cytokines in rat colon. RIPK2-IN-8 is used to study RIPK2-mediated signaling in inflammation and immunity and to validate RIPK2 as a therapeutic target for inflammatory diseases. The compound's mechanism of action involves inhibiting RIPK2 kinase activity, thereby blocking NOD1/2-mediated inflammatory responses.
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| Molecular Formula |
C18H21FN4O3S
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| Molecular Weight |
392.447746038437
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| Exact Mass |
392.131
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| CAS # |
2141969-56-2
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| PubChem CID |
131801159
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| Appearance |
White to off-white solid powder
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| LogP |
3
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
27
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| Complexity |
621
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S(C1C(=CC2=NC=C(C3C=C(N=C(C=3)N)F)N2C=1)OCC)(C(C)(C)C)(=O)=O
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| InChi Key |
QWDMZDSZMVJFFJ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H21FN4O3S/c1-5-26-13-8-17-21-9-12(11-6-15(19)22-16(20)7-11)23(17)10-14(13)27(24,25)18(2,3)4/h6-10H,5H2,1-4H3,(H2,20,22)
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| Chemical Name |
4-(6-tert-butylsulfonyl-7-ethoxyimidazo[1,2-a]pyridin-3-yl)-6-fluoropyridin-2-amine
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| Synonyms |
RIPK2-IN-8 RIPK2IN8 RIPK2 IN 8
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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 : ~31.25 mg/mL (~79.63 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3.13 mg/mL (7.98 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 31.3 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 | 2.5481 mL | 12.7405 mL | 25.4810 mL | |
| 5 mM | 0.5096 mL | 2.5481 mL | 5.0962 mL | |
| 10 mM | 0.2548 mL | 1.2740 mL | 2.5481 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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