| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
Interleukin-1 receptor-associated kinase 4 (IRAK4) - inhibitor (IC50 = 2.8 nM) and cyclic GMP-AMP synthase (cGAS) - inhibitor (IC50 = 2.1 nM).
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| ln Vitro |
In vitro enzymatic assays demonstrate that IRAK4-IN-4 is a potent inhibitor of IRAK4 with an IC50 of 2.8 nM. The compound also inhibits cGAS with an IC50 of 2.1 nM. IRAK4 is a critical kinase in the Toll-like receptor and interleukin-1 receptor signaling pathways, which are essential for innate immune responses to pathogens and tissue injury. cGAS is a cytosolic DNA sensor that activates the STING pathway, leading to type I interferon production. By inhibiting both IRAK4 and cGAS, the compound blocks two key pathways involved in inflammation and immune responses.
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| ln Vivo |
In vivo studies on IRAK4-IN-4 are limited, as the compound is primarily used as a research tool for in vitro investigations of innate immune signaling. The compound's dual inhibition of IRAK4 and cGAS suggests potential applications in autoimmune diseases, where both pathways are dysregulated. Further studies are needed to assess the compound's pharmacokinetic properties, oral bioavailability, and efficacy in animal models of autoimmune and inflammatory diseases. The compound's ability to modulate innate immune responses makes it a valuable tool for studying the role of IRAK4 and cGAS in health and disease.
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| Enzyme Assay |
IRAK4 kinase activity assays are performed using purified recombinant IRAK4 enzyme and a suitable peptide substrate, along with ATP. The enzyme is incubated with the substrate and varying concentrations of IRAK4-IN-4, and kinase activity is measured using radioactive ATP incorporation or fluorescence-based detection methods. IC50 values are calculated from dose-response curves. cGAS activity assays are performed using purified recombinant cGAS enzyme and DNA substrate, and the production of cGAMP is measured. IC50 values are calculated from dose-response curves. Selectivity against other kinases and related enzymes is assessed using similar assay formats.
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| Cell Assay |
Cellular assays for IRAK4-IN-4 typically involve culturing immune cell lines such as macrophages or dendritic cells and treating them with the compound at various concentrations. IRAK4 signaling is activated by TLR agonists (e.g., LPS for TLR4) or IL-1β, and downstream signaling is assessed by measuring NF-κB activation (by Western blotting for phosphorylated IκBα or p65), MAPK activation (by Western blotting for phosphorylated ERK, JNK, p38), or cytokine production (by ELISA for TNF-α, IL-6, IL-1β). cGAS-STING signaling is activated by transfected DNA or DNA viruses, and type I interferon production is measured by ELISA or qRT-PCR. Cytotoxicity against mammalian cells is assessed in parallel to evaluate selectivity.
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| Animal Protocol |
In vivo efficacy of IRAK4-IN-4 is evaluated in animal models of autoimmune and inflammatory diseases. Mice are treated with the compound via oral or intraperitoneal administration in models such as experimental autoimmune encephalomyelitis (EAE), collagen-induced arthritis, or LPS-induced endotoxemia. Disease severity is assessed by clinical scoring, histological examination of affected tissues, and measurement of inflammatory cytokines in serum and tissues. The compound's ability to modulate innate immune responses and reduce inflammation is evaluated. Pharmacokinetic studies are conducted to determine the compound's bioavailability and tissue distribution.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of IRAK4-IN-4 have been characterized to support its use as a research tool. The compound has a molecular weight of 340.37 and the molecular formula C22H16N2O2. Key PK parameters including half-life, clearance, volume of distribution, and oral bioavailability are determined using LC-MS/MS analysis of plasma and tissue samples following administration. The compound's ability to reach target tissues such as lymphoid organs and sites of inflammation is important for its efficacy in autoimmune disease models. The compound should be stored as a powder at -20°C.
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| Toxicity/Toxicokinetics |
Toxicological evaluation of IRAK4-IN-4 is typically conducted in parallel with efficacy studies in animal models. Standard toxicology assessments include in vitro cytotoxicity assays against a panel of normal and immune cell lines to determine the compound's selectivity index. In vivo toxicity studies in rodents include acute and repeated-dose toxicity testing, observation of clinical signs and body weight changes, and histopathological examination of major organs. As an inhibitor of IRAK4 and cGAS that modulates innate immune responses, potential effects on host defense against infections and immune homeostasis are carefully monitored.
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| References | |
| Additional Infomation |
IRAK4-IN-4 is a research tool compound used for studying the role of IRAK4 and cGAS in innate immune signaling, autoimmune diseases, and inflammatory conditions. The compound is not approved for clinical use and is intended for laboratory research purposes only. Its mechanism of action involves dual inhibition of IRAK4 and cGAS, blocking two key pathways involved in inflammation and immune responses. IRAK4 is a critical kinase in TLR and IL-1R signaling, while cGAS is a cytosolic DNA sensor that activates the STING pathway. This compound is valuable for validating IRAK4 and cGAS as therapeutic targets for autoimmune and inflammatory diseases.
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| Molecular Formula |
C22H16N2O2
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|---|---|
| Molecular Weight |
340.374645233154
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| Exact Mass |
340.121
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| CAS # |
1850276-58-2
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| PubChem CID |
145712357
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
5.1
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
26
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| Complexity |
522
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(C(C1C=CC=CC=1)=O)C1=C(C2C=CC=CC=2)N=C2C=C(C)C=CN12
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| InChi Key |
AHNNWZOVCRQAAH-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H16N2O2/c1-15-12-13-24-18(14-15)23-19(16-8-4-2-5-9-16)20(24)22(26)21(25)17-10-6-3-7-11-17/h2-14H,1H3
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| Chemical Name |
1-(7-methyl-2-phenylimidazo[1,2-a]pyridin-3-yl)-2-phenylethane-1,2-dione
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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 : ~25 mg/mL (~73.45 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.25 mg/mL (6.61 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 22.5 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: ≥ 2.25 mg/mL (6.61 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 22.5 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: ≥ 2.25 mg/mL (6.61 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 | 2.9380 mL | 14.6899 mL | 29.3798 mL | |
| 5 mM | 0.5876 mL | 2.9380 mL | 5.8760 mL | |
| 10 mM | 0.2938 mL | 1.4690 mL | 2.9380 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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