| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| Other Sizes |
| Targets |
IRAK4
IRAK4. |
|---|---|
| ln Vitro |
IRAK inhibitor 4 (trans) is a potent IRAK4 inhibitor with reported activity in the low nanomolar range (exact IC50 not publicly specified). The trans isomer may exhibit different pharmacokinetic or stereochemical properties compared to the cis form. It blocks the phosphorylation of downstream substrates in the TLR/IL-1R signaling cascade.
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| ln Vivo |
No in vivo activity data for IRAK inhibitor 4 (trans) is publicly available. As a potent IRAK4 inhibitor, it would be expected to show activity in animal models of inflammatory diseases such as LPS-induced endotoxemia, collagen-induced arthritis, or experimental autoimmune encephalomyelitis (EAE) upon oral or intraperitoneal administration.
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| Enzyme Assay |
Not available. A generic IRAK4 kinase assay can be used: recombinant human IRAK4 (10 ng) is incubated with biotinylated peptide substrate (100 microM) and ATP (10 microM) in 50 mM HEPES buffer (pH 7.5), 10 mM MgCl2, 1 mM DTT, 0.01% BSA, and 0.01% Tween-20. IRAK inhibitor 4 (trans) (0.1 nM - 10 microM) is added prior to ATP addition for 30 min at room temperature. Reaction is terminated with EDTA (50 mM), and phosphorylation is detected by TR-FRET using Eu-labeled anti-phospho substrate antibody and streptavidin-allophycocyanin.
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| Cell Assay |
Human THP-1 monocytes are differentiated into macrophages with PMA (50 ng/mL, 48 h). Cells are primed with LPS (100 ng/mL, 4 h), then treated with IRAK inhibitor 4 (trans) (0.01-10 microM, 1 h), followed by stimulation with IL-1beta (10 ng/mL) or Pam3CSK4 (1 microg/mL) for 6-24 h. Supernatants are collected for TNF-alpha and IL-6 ELISA. Cell lysates are analyzed by Western blot for phosphorylation of IRAK4, IRAK1, and IkappaBalpha. NF-kappaB activation is assessed by luciferase reporter assay in HEK293 cells co-transfected with NF-kappaB-luciferase.
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| Animal Protocol |
No animal protocol is published. A generic model for testing IRAK4 inhibitors in vivo: female BALB/c mice (6-8 weeks, n=8/group) receive oral administration of IRAK inhibitor 4 (trans) (10-50 mg/kg) 1 h prior to intraperitoneal LPS injection (5-10 mg/kg). Blood is collected 2-4 h post-LPS challenge, and serum TNF-alpha, IL-6, and IL-1beta levels are measured by ELISA. Livers and spleens are harvested for qPCR analysis of pro-inflammatory cytokine mRNA expression.
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| ADME/Pharmacokinetics |
No PK data available. Generic PK for IRAK4 inhibitors: male SD rats or C57BL/6 mice receive IV (2-5 mg/kg) and oral (10-30 mg/kg) administration of test compound. Blood samples are collected at 0.083, 0.25, 0.5, 1, 2, 4, 6, 8, 12, and 24 h. Plasma is analyzed by LC-MS/MS. PK parameters including t1/2, Cmax, Tmax, AUC, Cl, Vd, and oral bioavailability (F%) are calculated.
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| Toxicity/Toxicokinetics |
No toxicity data reported. Generic subchronic oral toxicity study: Sprague-Dawley rats (10/sex/group) receive IRAK inhibitor 4 (trans) at doses of 10, 30, 100 mg/kg/day by oral gavage for 28 days. Endpoints include body weight, food consumption, hematology (CBC, differential), serum chemistry (ALT, AST, BUN, creatinine, total protein, albumin), and histopathology of major organs (liver, kidney, spleen, thymus, heart, lung, GI tract, bone marrow, brain, gonads).
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| References | |
| Additional Infomation |
IRAK inhibitor 4 (trans) is a research compound referenced in patent WO2008030584 and is not approved for clinical use. It has not entered clinical trials and is intended solely for laboratory research applications to study IRAK4 biology and to validate IRAK4 as a therapeutic target for inflammatory diseases. The trans isomer may be used for stereochemical optimization studies.
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| Molecular Formula |
C33H35F3N6O3
|
|---|---|
| Molecular Weight |
620.664617776871
|
| Exact Mass |
620.272
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| CAS # |
2070014-89-8
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| Related CAS # |
IRAK inhibitor 4;1012104-68-5
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| PubChem CID |
24797387
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| Appearance |
Light yellow to yellow solid powder
|
| LogP |
7.6
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| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
9
|
| Heavy Atom Count |
45
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| Complexity |
982
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
QZMAOGLWCNTFCG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C33H35F3N6O3/c1-19(2)15-16-37-31(44)21-8-14-28-27(18-21)38-32(42(28)22-9-11-23(43)12-10-22)39-30-25-17-20(7-13-26(25)40-41-30)24-5-3-4-6-29(24)45-33(34,35)36/h3-8,13-14,17-19,22-23,43H,9-12,15-16H2,1-2H3,(H,37,44)(H2,38,39,40,41)
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| Chemical Name |
1-(4-hydroxycyclohexyl)-N-(3-methylbutyl)-2-[[5-[2-(trifluoromethoxy)phenyl]-1H-indazol-3-yl]amino]benzimidazole-5-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: ≥ 38 mg/mL (61.23 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 | 1.6112 mL | 8.0559 mL | 16.1119 mL | |
| 5 mM | 0.3222 mL | 1.6112 mL | 3.2224 mL | |
| 10 mM | 0.1611 mL | 0.8056 mL | 1.6112 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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