| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg | |||
| Other Sizes |
| Targets |
p38alpha-IN-4 targets p38α mitogen-activated protein kinase (MAPK), a serine/threonine kinase that plays a critical role in cellular responses to stress and inflammation. The p38 MAPK pathway is activated by various stimuli, including inflammatory cytokines and environmental stress, and regulates the production of pro-inflammatory mediators. p38alpha-IN-4 is a potent and selective inhibitor of p38 MAPK, with an IC50 of 68 nM. By inhibiting p38 MAPK, the compound reduces the production of pro-inflammatory cytokines and may have therapeutic potential in inflammatory diseases.
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| ln Vitro |
In vitro, p38alpha-IN-4 is a potent inhibitor of p38 MAPK with an IC50 of 68 nM. Its activity is typically measured using kinase assays with recombinant p38 MAPK and a peptide substrate. The compound is selective for p38 MAPK over other kinases. These in vitro studies confirm the compound's potent and selective p38 MAPK inhibitory activity.
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| ln Vivo |
p38 MAPK-IN-1 (Compound 4; 1 mg/kg i.v., 10 mg/kg oral) suppresses TNFα production dose-dependently with an ED50 of 0.5 mg/kg[1]; it has a t1/2 of 7.4 hours, a CL of 2.7 mL/min/kg i.v., and a Cmax of 5.3 μM in males PO in Wistar rats.
In vivo, p38alpha-IN-4 has sustained levels, low clearance, and good bioavailability. It has shown excellent action in a chronic model of arthritis. These findings suggest that p38alpha-IN-4 has the proper balance between potency and pharmacokinetics for further study in inflammatory diseases. However, specific in vivo protocols and results are not detailed in standard product descriptions. |
| Enzyme Assay |
In vitro enzyme assays for p38alpha-IN-4 measure its inhibition of p38 MAPK activity. Recombinant p38 MAPK 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 is determined from the dose-response curve. For p38alpha-IN-4, the IC50 is 68 nM. Selectivity is assessed by testing the compound against a panel of other kinases.
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| Cell Assay |
In vitro cell-based assays for p38alpha-IN-4 are used to study its effects on p38 MAPK signaling and inflammation. Cells are treated with the compound and then stimulated with an inflammatory stimulus, such as lipopolysaccharide (LPS) or TNF-α. The production of pro-inflammatory cytokines, such as IL-6 and TNF-α, is measured by ELISA. The phosphorylation of p38 MAPK and its downstream targets is assessed by Western blotting. These assays confirm the compound's activity as a p38 MAPK inhibitor.
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| Animal Protocol |
Animal/Disease Models: Male Wistar rat [1]
Doses: 10 mg/kg orally, 1 mg/kg intravenously (iv) (iv)(iv) (pharmacokinetic/PK/PK analysis) Route of Administration: oral and intravenous (iv) (iv)injection Experimental Results: t1/2 is 7.4 hrs (hrs (hours)), CL is 2.7 mL/min iv/kg, oral Cmax is 5.3 μM. In vivo animal experiments for p38alpha-IN-4 have been conducted in a chronic model of arthritis. In a typical study, the compound is administered to animals with induced arthritis, and disease severity is assessed by measuring joint inflammation, cartilage damage, and bone erosion. The compound's ability to reduce disease severity is assessed. These studies provide evidence for the in vivo efficacy of p38alpha-IN-4. |
| ADME/Pharmacokinetics |
p38alpha-IN-4 has a molecular weight of 348.35 g/mol and a molecular formula of C21H14F2N2O. It has a CAS number of 1006378-90-0. It is a solid compound. For storage, it is recommended to keep the powder at -20°C. Pharmacokinetic properties have been characterized. p38alpha-IN-4 has sustained levels, low clearance, and good bioavailability.
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| Toxicity/Toxicokinetics |
Detailed toxicity data for p38alpha-IN-4 is not provided in standard product descriptions. As a research compound, its toxicity profile has not been extensively characterized. p38alpha-IN-4 is a p38 MAPK inhibitor, and its toxicity would be related to its effects on p38 MAPK signaling in normal tissues. However, comprehensive toxicological studies have not been reported. As with all research chemicals, standard laboratory safety precautions should be followed.
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| References | |
| Additional Infomation |
p38alpha-IN-4 is a research compound and is not approved for any clinical or therapeutic use. It is a novel, potent, and selective inhibitor of p38α MAPK. It is a naphthyridine N-oxide compound. p38alpha-IN-4 inhibits p38 MAPK with an IC50 of 68 nM and has sustained levels, low clearance, and good bioavailability. It has shown excellent action in a chronic model of arthritis. p38alpha-IN-4 is a valuable research tool for studying the p38 MAPK signaling pathway and inflammatory diseases.
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| Molecular Formula |
C21H14F2N2O
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|---|---|
| Molecular Weight |
348.35
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| Exact Mass |
348.107
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| CAS # |
1006378-90-0
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| PubChem CID |
24899733
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| Appearance |
Off-white to yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
527.0±50.0 °C at 760 mmHg
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| Flash Point |
272.5±30.1 °C
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| Vapour Pressure |
0.0±1.3 mmHg at 25°C
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| Index of Refraction |
1.622
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| LogP |
2.46
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
26
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| Complexity |
479
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=CC=CC=C1C2=[N+](C=CC3=C(C=CN=C32)C4=C(C=C(C=C4)F)F)[O-]
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| InChi Key |
BSZQSLWNMVTKJT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H14F2N2O/c1-13-4-2-3-5-15(13)21-20-18(9-11-25(21)26)16(8-10-24-20)17-7-6-14(22)12-19(17)23/h2-12H,1H3
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| Chemical Name |
4-(2,4-difluorophenyl)-8-(2-methylphenyl)-7-oxido-1,7-naphthyridin-7-ium
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| Synonyms |
p38alpha-IN-4 p38alphaIN4 p38alpha IN 4 p38alpha-inhibitor-4 p38 MAP Kinase Inhibitor XI p38alpha inhibitor 4
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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 : ~33.33 mg/mL (~95.41 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.83 mg/mL (2.38 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 8.3 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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: ≥ 0.83 mg/mL (2.38 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 8.3 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. View More
Solubility in Formulation 3: ≥ 0.83 mg/mL (2.38 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8707 mL | 14.3534 mL | 28.7068 mL | |
| 5 mM | 0.5741 mL | 2.8707 mL | 5.7414 mL | |
| 10 mM | 0.2871 mL | 1.4353 mL | 2.8707 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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