| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| Other Sizes |
| Targets |
IRAK4-IN-20 targets IRAK4, a key upstream kinase in the IL-1 receptor (IL-1R) and Toll-like receptor (TLR) signaling pathways. IRAK4 plays a central role in the body's first line of defense against invading microbes and is critical for driving the production of inflammatory cytokines. By inhibiting IRAK4, the compound blocks the downstream signaling cascade, reducing the production of pro-inflammatory mediators.
|
|---|---|
| ln Vitro |
IRAK4-IN-20 (compound BAY-1834845), when administered ex vivo to LPS-stimulated human peripheral blood mononuclear cells (PBMC), effectively lowers the release of inflammatory cytokines [1].
In vitro, IRAK4-IN-20 is a potent inhibitor of IRAK4 with an IC50 of 3.55 nM. This demonstrates its high potency in inhibiting the kinase activity of IRAK4. Specific cellular assay data, such as effects on cytokine production in immune cells, are not detailed in the available sources. |
| ln Vivo |
IRAK4-IN-20 (compound BAY-1834845) (150 mg/kg; oral; once or twice) is beneficial in avoiding acute respiratory distress syndrome in mice [1].
In vivo, IRAK4-IN-20 has shown anti-inflammatory, antitumor, and anticancer effects. It is being studied for its potential to treat acute respiratory distress syndrome (ARDS). Specific in vivo efficacy data, such as effects in animal models of ARDS or inflammation, are not detailed in the available sources. |
| Enzyme Assay |
A cell-free assay for IRAK4-IN-20 involves measuring its inhibition of IRAK4 kinase activity. In this assay, recombinant IRAK4 is incubated with a peptide substrate and ATP in the presence of varying concentrations of the compound. The incorporation of phosphate into the substrate is measured, and the IC50 value is calculated. For IRAK4-IN-20, the IC50 is 3.55 nM.
|
| Cell Assay |
Cellular assays for IRAK4-IN-20 would typically involve assessing its effects on IL-1R/TLR signaling in immune cells. Cells are treated with the compound and stimulated with a TLR agonist or IL-1β. The production of inflammatory cytokines, such as IL-6 and TNF-α, is measured. The compound's ability to inhibit IRAK4 activity in cells is reflected by a reduction in cytokine production.
|
| Animal Protocol |
Animal/Disease Models: Female balb/c (Bagg ALBino) mouse (6-7 weeks old), LPS-induced ARDS mouse model [1]
Doses: 150 mg/kg Route of Administration: Orally, 30 minutes before or after LPS modeling Modeling results at 4 hrs (hrs (hours)) and 12 hrs (hrs (hours)): inflammatory cells infiltrating lung tissue and neutrophil counts in BALF were Dramatically diminished. Effectively reduces the number of total T cells, monocytes and macrophages. Characteristics of naive lymphocytes and stromal cells such as endothelial cells, chondrocytes, and smooth muscle cells are largely retained. Modulates inflammatory and innate immune genes more effectively than dexamethasone. In vivo animal experiments for IRAK4-IN-20 are not described in the available sources. As a compound with anti-inflammatory potential, it could be evaluated in animal models of ARDS or other inflammatory diseases. However, no specific protocols or data are provided. |
| ADME/Pharmacokinetics |
IRAK4-IN-20 is an orally active compound. Specific pharmacokinetic parameters, such as half-life and bioavailability, are not provided in the available sources. The compound is intended for research use.
|
| Toxicity/Toxicokinetics |
Toxicity data for IRAK4-IN-20 are not provided in the available sources. As a research compound, it is intended for research use only and is not for human consumption. Standard laboratory safety precautions should be observed.
|
| References | |
| Additional Infomation |
IRAK4-IN-20 (CAS: 1931994-80-7) is a potent and orally active IRAK4 inhibitor. It is also known as Compound BAY-1834845. The compound has anti-inflammatory, antitumor, and anticancer effects and is being investigated for the treatment of acute respiratory distress syndrome (ARDS). It is not an approved drug and is strictly for research purposes.
|
| Molecular Formula |
C22H25F3N4O3
|
|---|---|
| Molecular Weight |
450.45
|
| Exact Mass |
450.187
|
| CAS # |
1931994-80-7
|
| PubChem CID |
121364971
|
| Appearance |
White to light yellow solid powder
|
| LogP |
3.1
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
32
|
| Complexity |
673
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C(C)(O)(C1C(=CC2C(C=1)=NN(CCC(C)(C)O)C=2)NC(=O)C1=CC=CC(=N1)C(F)(F)F)C
|
| InChi Key |
NWFPCWIBSBZRGV-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C22H25F3N4O3/c1-20(2,31)8-9-29-12-13-10-17(14(21(3,4)32)11-16(13)28-29)27-19(30)15-6-5-7-18(26-15)22(23,24)25/h5-7,10-12,31-32H,8-9H2,1-4H3,(H,27,30)
|
| Chemical Name |
N-[2-(3-hydroxy-3-methylbutyl)-6-(2-hydroxypropan-2-yl)indazol-5-yl]-6-(trifluoromethyl)pyridine-2-carboxamide
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| 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 | 2.2200 mL | 11.1000 mL | 22.2000 mL | |
| 5 mM | 0.4440 mL | 2.2200 mL | 4.4400 mL | |
| 10 mM | 0.2220 mL | 1.1100 mL | 2.2200 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.
Link: https://clinicaltrials.gov/ct2/show/NCT03965728
Conditions:Healthy VolunteersLink: https://clinicaltrials.gov/ct2/show/NCT05003089
Conditions:Immune Mediated Inflammatory DiseasesLink: https://clinicaltrials.gov/ct2/show/NCT03540615
Conditions:Arthritis, RheumatoidProducts are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
