| Size | Price | Stock | Qty |
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| Targets |
The primary target is IRAK4, a key kinase in the MyD88-dependent signaling pathway downstream of Toll-like receptors (TLRs) and IL-1 receptors. It also targets TAK1. By inhibiting IRAK4 and, to a lesser extent, TAK1, the compound prevents the activation of NF-kappaB and MAP kinase pathways, leading to a potent suppression of the expression of pro-inflammatory cytokines such as IL-23, IL-6, and TNF-alpha.
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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-21 inhibits IRAK4 with an IC50 of 5 nM and TAK1 with an IC50 of 56 nM. In cellular models, it exhibits potent inhibition of IL-23 production with an IC50 of 0.17 microM, demonstrating its capacity to modulate the Th17 immune axis, which is central to the pathology of psoriasis and other autoimmune diseases. |
| 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-21 is not detailed. However, with its oral activity and mechanism of action as an IRAK4/TAK1 inhibitor, it is likely evaluated in murine models of psoriasis, such as the imiquimod-induced model. A typical study would use oral administration to assess the reduction in skin inflammation, epidermal thickness, and immune cell infiltration. |
| Enzyme Assay |
The assay for IRAK4-IN-21 is a standard biochemical kinase inhibition assay. Purified recombinant IRAK4 or TAK1 enzyme is incubated with a peptide substrate, ATP, and varying concentrations of the inhibitor in reaction buffer. After incubation at room temperature or 30degC, the reaction is quenched, and the amount of ADP produced (indicative of kinase activity) is measured using a luminescent ADP-Glo assay. The IC50 values are calculated by plotting inhibitor concentration vs. remaining kinase activity.
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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 0.17 and 0.51 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 0.20 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 0.47 µM. The cellular activity is assessed using primary human monocytes or a monocytic cell line (e.g., THP-1). Cells are seeded in a 96-well plate and pre-treated with IRAK4-IN-21 at various concentrations. They are then stimulated with a TLR agonist (e.g., LPS). After overnight incubation (16-24 hours), the supernatant is collected, and the concentration of IL-23 is measured using a sandwich ELISA kit specific for human IL-23. The IC50 is calculated as the concentration required to inhibit 50% of the maximal IL-23 production. |
| 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 54%, the plasma concentration at 0.5 hrs (hrs (hours)) was 2877 ng/mL, and the plasma concentration at 2 hrs (hrs (hours)) was 496 ng/mL. In vivo efficacy is evaluated in an imiquimod (IMQ)-induced psoriasis-like skin inflammation mouse model. Female BALB/c or C57BL/6 mice have their shaved backs treated with 5% IMQ cream for 6 consecutive days to induce a psoriasis-like phenotype. IRAK4-IN-21 is administered orally at doses ranging from 10 to 50 mg/kg daily. The disease severity is scored using the PASI system. On day 6, the mice are euthanized, and skin tissue is collected for histology (H&E staining, epidermal thickness) and cytokine analysis (qPCR or ELISA for IL-17A, IL-22, IL-23). |
| ADME/Pharmacokinetics |
IRAK4-IN-21 is designed to be “orally active.” Specific quantitative pharmacokinetic parameters (Cmax, T1/2, AUC, F%) are not provided in the search results. However, the compound's ability to achieve therapeutic effects when administered orally indicates it has sufficient absorption, metabolic stability, and systemic exposure to modulate its target in disease-relevant tissues like the skin.
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| Toxicity/Toxicokinetics |
Specific toxicological data for IRAK4-IN-21 are not detailed. As an inhibitor of IRAK4 and TAK1-two critical components of the innate immune response-the primary on-target safety concern is an increased susceptibility to infections due to immunosuppression. Standard toxicological assessment would include evaluating the compound's effect on hematopoietic cell populations and its ability to protect against bacterial or viral challenges in animal models.
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| References | |
| Additional Infomation |
IRAK4-IN-21 is a research-grade compound that is structurally similar to its analog IRAK4-IN-22, differing by a single methyl group. Both are potent, selective IRAK4/TAK1 inhibitors. These compounds are used as chemical probes to dissect the relative contributions of IRAK4 and TAK1 in inflammatory signaling. As of the latest updates, they are pre-clinical research tools and have not been approved for clinical use.
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| Molecular Formula |
C28H28FN7O2
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|---|---|
| Molecular Weight |
513.57
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| Exact Mass |
513.228
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| CAS # |
2170694-04-7
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| PubChem CID |
132256209
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| Appearance |
White to off-white solid powder
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| LogP |
3.4
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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(C3=CC(F)=CN=C3)=CN=C(NC3=CC=CC(C(N4CCCC4)=O)=C3)N=1)[C@H]2C(N)=O
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| InChi Key |
KYNJAMYDYPTYDZ-GCRLEYHISA-N
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| InChi Code |
InChI=1S/C28H28FN7O2/c29-20-11-19(13-31-14-20)22-15-32-28(33-21-5-3-4-18(12-21)27(38)36-8-1-2-9-36)35-26(22)34-24-17-7-6-16(10-17)23(24)25(30)37/h3-7,11-17,23-24H,1-2,8-10H2,(H2,30,37)(H2,32,33,34,35)/t16-,17+,23+,24-/m1/s1
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| Chemical Name |
(1S,2S,3R,4R)-3-[[5-(5-fluoropyridin-3-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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