| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
The compound primarily targets IRAK4, a serine/threonine kinase that plays a crucial role in the signaling pathways downstream of Toll-like receptors (TLRs) and interleukin-1 receptors (IL-1Rs). It also potently inhibits TAK1, another key kinase in these and other stress response pathways. By inhibiting these two nodes, the compound effectively blocks the MyD88-dependent signaling pathway and the downstream activation of NF-kappaB and MAP kinases.
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| ln Vitro |
IRAK4-IN-21 (four-fold serial dilution, commencing at 10 µM; one hour) decreases MIP-1β in human whole blood, IL-6 in HUVEC cells, and IL-23 in THP-1 and DC cells[1].
In biochemical assays, IRAK4-IN-22 exhibits potent inhibition of IRAK4 with an IC50 of 3 nM and of TAK1 with an IC50 of 17 nM. It shows selectivity for these targets over other kinases. In cellular models, the compound effectively inhibits the production of pro-inflammatory cytokines, particularly IL-23, with an IC50 of 0.10 microM, indicating strong anti-inflammatory activity in immune cells. |
| ln Vivo |
In acute animal model experiments, IRAK4-IN-21 (75 mg/kg; oral; single dosage) has demonstrated a moderate level of efficacy in suppressing the generation of IL-6 [1].
Specific in vivo data for IRAK4-IN-22 is not detailed. However, given its oral activity and potent anti-inflammatory mechanism (inhibition of IRAK4 and TAK1 leading to blockade of IL-23 production), it is intended for use in animal models of autoimmune diseases, such as the imiquimod-induced psoriasis model or the collagen-induced arthritis model. A typical protocol would involve oral administration to mice to assess the reduction of skin inflammation, ear thickness, or paw swelling. |
| Enzyme Assay |
The biochemical assay is a standard kinase inhibition assay using ADP-Glo or radiometric methods. Purified recombinant active IRAK4 or TAK1 kinase is incubated with a specific peptide substrate, ATP (at Km concentration), and varying concentrations of the inhibitor in a reaction buffer. After incubation at 30degC, the reaction is stopped, and the amount of ADP produced (or 32P incorporated) is measured. The IC50 is calculated from the dose-response curve.
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: THP-1, DC cells (primed with IFN-γ) Tested Concentrations: 10 µM (4-fold serial dilution starting from 10 µM) Incubation Duration: 1 hour (pre-incubation) Experimental Results: Inhibition of THP- 1 and IL-23 levels in DC cell supernatants, with IC50s of 0.10 and 0.11 µM, respectively. Cell viability assay[1] Cell Types: HUVEC cells (IL-1β stimulation) Tested Concentrations: 10 µM (4-fold serial dilution starting from 10 µM) Incubation Duration: 1 hour (pre-incubation) Experimental Results: Inhibition of IL levels HUVEC cell supernatant -6 in, IC50 is 0.11 µM. Cell viability assay[1] Cell Types: Human whole blood (IL-1β stimulation) Tested Concentrations: 10 µM (4-fold serial dilution starting from 10 µM) Incubation Duration: 1 hour (pre-incubation) Experimental Results: Inhibition of MIP in human whole blood -1β, IC50 is 0.51 µM. The cellular assay is performed using a cell line that produces IL-23 upon stimulation, such as primary human monocytes or monocytic THP-1 cells. The cells are pre-treated with varying concentrations of IRAK4-IN-22, then stimulated with an appropriate ligand (e.g., LPS for TLR4 activation). After 16-24 hours, the cell culture supernatant is collected, and the concentration of IL-23 is measured using a specific human IL-23 ELISA kit. The IC50 for inhibition of IL-23 production is calculated. |
| Animal Protocol |
Animal/Disease Models: BALB/c mouse (acute mouse model; IL-1β stimulation) [1].
Doses: 75 mg/kg Route of Administration: Oral; single dose (pretreatment). Experimental Results: The inhibition rate of IL-6 was 64%, the plasma concentration at 0.5 hrs (hrs (hours)) was 6817 ng/mL, and the plasma concentration at 2 hrs (hrs (hours)) was 700 ng/mL. Although specific protocols are not detailed, a typical in vivo study would use the Imiquimod (IMQ)-induced psoriasis mouse model. Female C57BL/6 mice are topically treated with IMQ cream on the shaved back skin for 5-7 consecutive days to induce psoriasis-like skin inflammation. IRAK4-IN-22 is administered orally at a dose of e.g., 10-50 mg/kg once daily. Disease severity is assessed daily using a clinical Psoriasis Area and Severity Index (PASI) score, as well as by measuring ear thickness. Skin samples are collected for histological analysis and cytokine measurement. |
| ADME/Pharmacokinetics |
IRAK4-IN-22 is described as an “orally active” compound. While specific PK parameters are not detailed, its design as a drug candidate for autoimmune diseases suggests it has properties favorable for oral administration, including sufficient metabolic stability and bioavailability. Such properties are essential for therapeutic use in chronic diseases like psoriasis.
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| Toxicity/Toxicokinetics |
Specific toxicological data for IRAK4-IN-22 are not detailed. As an inhibitor of key immune signaling pathways, its primary on-target toxicity could be immunosuppression, potentially leading to an increased risk of infections. This is a common class-effect of IRAK4 inhibitors. The therapeutic window would be determined by the balance between efficacy (e.g., reducing skin inflammation) and the degree of systemic immunosuppression in animal models.
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| References | |
| Additional Infomation |
IRAK4-IN-22 is a research-grade chemical tool for investigating the role of IRAK4 and TAK1 kinases in inflammatory signaling pathways. As a dual inhibitor, it is a powerful tool for studying the MyD88-dependent pathway. It represents a pre-clinical lead compound. As of the latest updates, it has not been approved for clinical use and is exclusively available for research purposes.
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| Molecular Formula |
C28H28FN7O2
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| Molecular Weight |
513.566028594971
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| Exact Mass |
513.228
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| CAS # |
2170694-05-8
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| PubChem CID |
132256204
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| Appearance |
White to off-white solid powder
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| LogP |
3.7
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
38
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| Complexity |
898
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| Defined Atom Stereocenter Count |
4
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| SMILES |
[C@]12([H])C[C@]([H])(C=C1)[C@@H](NC1C(C3C=CN=C(F)C=3)=CN=C(NC3=CC=CC(C(N4CCCC4)=O)=C3)N=1)[C@H]2C(N)=O
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| InChi Key |
FLZAOAIEJUXTAH-HJOCRKTISA-N
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| InChi Code |
InChI=1S/C28H28FN7O2/c29-22-14-16(8-9-31-22)21-15-32-28(33-20-5-3-4-19(13-20)27(38)36-10-1-2-11-36)35-26(21)34-24-18-7-6-17(12-18)23(24)25(30)37/h3-9,13-15,17-18,23-24H,1-2,10-12H2,(H2,30,37)(H2,32,33,34,35)/t17-,18+,23+,24-/m1/s1
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| Chemical Name |
(1S,2S,3R,4R)-3-[[5-(2-fluoropyridin-4-yl)-2-[3-(pyrrolidine-1-carbonyl)anilino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-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 : ~100 mg/mL (~194.72 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 | 1.9472 mL | 9.7358 mL | 19.4715 mL | |
| 5 mM | 0.3894 mL | 1.9472 mL | 3.8943 mL | |
| 10 mM | 0.1947 mL | 0.9736 mL | 1.9472 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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