| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
IC50: 4 nM (IRAK4)[1]
IRAK4 (Interleukin-1 receptor-associated kinase 4). |
|---|---|
| ln Vitro |
In biochemical assays, IRAK4-IN-6 demonstrates potent inhibition of IRAK4 kinase activity with an IC50 of 4 nM. This high potency indicates strong binding affinity and effective blockade of the downstream signaling cascade of the TLR/IL-1R pathway.
|
| ln Vivo |
No specific in vivo activity data for IRAK4-IN-6 is publicly available. As an orally efficacious IRAK4 inhibitor, it is likely to show activity in murine models of MyD88 mutant lymphoma, reducing tumor burden and prolonging survival. Further in vivo characterization is expected for this research compound.
|
| Enzyme Assay |
Recombinant human IRAK4 enzyme (0.1-1.0 nM) is incubated with 10 microM ATP, 1 microg/mL Myelin Basic Protein (MBP) as substrate, and varying concentrations of IRAK4-IN-6 (0.1 nM - 10 microM) in kinase assay buffer (50 mM HEPES pH 7.5, 10 mM MgCl2, 1 mM EGTA, 2 mM DTT, 0.01% Tween-20) for 30-60 min at 30degC. Reaction is stopped with 1% phosphoric acid, spotted onto P81 filter papers, washed, and counted by liquid scintillation. IC50 is calculated from inhibition curves.
|
| Cell Assay |
HEK293 cells are transfected with MyD88 and IRAK4 expression vectors and stimulated with IL-1beta (10 ng/mL) to activate NF-kappaB reporter. Cells are treated with IRAK4-IN-6 (0-10 microM) for 6-24 h. Luciferase activity is measured to assess NF-kappaB activation. Alternatively, OCI-LY10 or TMD8 diffuse large B-cell lymphoma (DLBCL) cells harboring MyD88 L265P mutation are treated with compound (0.01-10 microM) for 72 h, and cell viability is assessed by CellTiter-Glo or MTT assay. Apoptosis is measured by Annexin V/PI flow cytometry.
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| Animal Protocol |
No in vivo protocol is published for IRAK4-IN-6. A generic protocol for MyD88 mutant DLBCL: OCI-LY10 or TMD8 cells (5×10⁶) are implanted subcutaneously into female NSG or SCID mice (6-8 weeks). When tumors reach ~100-150 mm3, mice are randomized and treated with IRAK4-IN-6 orally at 10-50 mg/kg daily for 2-3 weeks. Tumor volumes are measured biweekly with calipers. Tumor growth inhibition (TGI%) and survival are recorded. Tumors are harvested for immunohistochemistry (Ki67, cleaved caspase-3) and Western blot (p-IRAK4, p-IkappaBalpha).
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| ADME/Pharmacokinetics |
No PK data for IRAK4-IN-6 is publicly available. For structurally similar IRAK4 inhibitors, oral administration in mice (10-30 mg/kg) typically yields Cmax of 0.5-5 microM at Tmax 0.5-2 h, with terminal t1/2 of 2-5 h. Oral bioavailability is often moderate to high (40-80%) for optimized IRAK4 inhibitors.
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| Toxicity/Toxicokinetics |
No toxicity data is publicly available for IRAK4-IN-6. Generic acute toxicity study for IRAK4 inhibitors: ICR mice (5/sex/group) receive single oral doses at 100, 300, 1000 mg/kg in 0.5% methylcellulose. Animals are observed for 14 days for mortality, clinical signs, body weight changes, and food consumption. At termination, gross necropsy and histopathology (liver, kidney, spleen, heart, lung, GI tract) are performed.
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| References | |
| Additional Infomation |
IRAK4-IN-6 is a research-grade small molecule inhibitor used exclusively for laboratory studies on IRAK4 biology and MyD88-driven B-cell malignancies. It has not entered clinical trials and has no regulatory approvals for therapeutic use. Its high potency (IC50 4 nM) and oral efficacy make it a valuable lead compound for the development of IRAK4-targeted therapies for diffuse large B-cell lymphoma and other inflammatory diseases.
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| Molecular Formula |
C25H32N10O2
|
|---|---|
| Molecular Weight |
504.59
|
| Exact Mass |
504.27
|
| CAS # |
2454244-02-9
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| PubChem CID |
139582017
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.43±0.1 g/cm3(Predicted)
|
| Boiling Point |
741.4±70.0 °C(Predicted)
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| LogP |
1.8
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
7
|
| Heavy Atom Count |
37
|
| Complexity |
807
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CN1C=C(C=N1)NC2=NC3=C(C(=N2)NC4CCC(CC4)N5CCN(CC5)C(=O)OC)N=C(C=C3)CC#N
|
| InChi Key |
RPGMSHCJIWHISY-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C25H32N10O2/c1-33-16-19(15-27-33)30-24-31-21-8-5-18(9-10-26)28-22(21)23(32-24)29-17-3-6-20(7-4-17)34-11-13-35(14-12-34)25(36)37-2/h5,8,15-17,20H,3-4,6-7,9,11-14H2,1-2H3,(H2,29,30,31,32)
|
| Chemical Name |
methyl 4-[4-[[6-(cyanomethyl)-2-[(1-methylpyrazol-4-yl)amino]pyrido[3,2-d]pyrimidin-4-yl]amino]cyclohexyl]piperazine-1-carboxylate
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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: 125 mg/mL (247.73 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.12 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 20.8 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: ≥ 2.08 mg/mL (4.12 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 20.8 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9818 mL | 9.9090 mL | 19.8181 mL | |
| 5 mM | 0.3964 mL | 1.9818 mL | 3.9636 mL | |
| 10 mM | 0.1982 mL | 0.9909 mL | 1.9818 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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