| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
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| Other Sizes |
| Targets |
p38α 1.2 μM (IC50)
The primary target of p38α inhibitor 4 is p38α MAPK (mitogen-activated protein kinase α). p38α is a member of the p38 MAPK family, which plays a critical role in cellular stress responses, inflammation, and apoptosis. p38α inhibitor 4 is a selective allosteric inhibitor, meaning it binds to a site distinct from the ATP-binding pocket. This allosteric mechanism provides selectivity for p38α over other p38 isoforms (p38β, p38γ, and p38δ). |
|---|---|
| ln Vitro |
p38α inhibitor 4 has an IC50 of 1.2 μM for inhibiting p38α. It exhibits no activity against p38β, p38γ, and p38δ, demonstrating high selectivity for the p38α isoform. As an allosteric inhibitor, it offers potential advantages in selectivity and the ability to modulate kinase activity in a non-competitive manner. The compound is used to study diabetes, pain, and chronic inflammation.
|
| ln Vivo |
In vivo, p38α inhibitor 4 is used to study the role of p38α in diabetes, pain, and chronic inflammation. By selectively inhibiting p38α, the compound can modulate inflammatory responses and pain signaling. Its efficacy would be assessed in animal models of these diseases, with endpoints including reduction of inflammatory markers, alleviation of pain, and improvement in metabolic parameters.
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| Enzyme Assay |
In vitro enzyme activity assays for p38α inhibitor 4 typically involve measuring its ability to inhibit p38α kinase activity. Recombinant p38α enzyme is incubated with its substrate in the presence of ATP and increasing concentrations of the compound. Kinase activity is measured by detecting substrate phosphorylation, and the IC50 is determined from the dose-response curve. The reported IC50 is 1.2 μM. Selectivity is confirmed by testing against p38β, p38γ, and p38δ.
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| Cell Assay |
Cellular assays for p38α inhibitor 4 involve treating cells with the compound and measuring inhibition of p38α-mediated signaling. Cells are stimulated with inflammatory stimuli (such as LPS or TNF-α) in the presence of increasing concentrations of the compound. Readouts include inhibition of p38α phosphorylation, downstream signaling (e.g., MAPKAPK2 phosphorylation), and production of pro-inflammatory cytokines.
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| Animal Protocol |
In vivo efficacy of p38α inhibitor 4 would be evaluated in animal models of diabetes, pain, and chronic inflammation. The compound could be administered orally or via injection. Efficacy endpoints would include reduction of inflammatory markers, alleviation of pain, and improvement in metabolic parameters. Its effects on p38α signaling in target tissues would be assessed by Western blot or immunohistochemistry.
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| ADME/Pharmacokinetics |
p38α inhibitor 4 has a molecular weight of 347.22 and a molecular formula of C14H7F6N3O. It is a selective allosteric inhibitor of p38α with an IC50 of 1.2 μM. The compound exhibits no activity against p38β, p38γ, and p38δ. It is used to study diabetes, pain, and chronic inflammation. The compound is for research use only and is not intended for human therapeutic use.
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| Toxicity/Toxicokinetics |
No specific toxicity data is available for p38α inhibitor 4 in the provided literature. As a research compound, its safety profile would be an important consideration for in vivo applications. Potential toxicities could be related to its effects on p38α-mediated inflammatory and stress responses in various tissues. Standard preclinical safety studies would be required to evaluate its safety for potential therapeutic applications. The compound is for research use only and is not intended for human therapeutic use.
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| References | |
| Additional Infomation |
p38α inhibitor 4 is a selective allosteric inhibitor of p38α MAPK with an IC50 of 1.2 μM. It exhibits no activity against p38β, p38γ, and p38δ. The compound has a molecular formula of C14H7F6N3O and a molecular weight of 347.22. p38α inhibitor 4 is used to study diabetes, pain, and chronic inflammation. As an allosteric inhibitor, it offers potential advantages in selectivity over ATP-competitive inhibitors.
|
| Molecular Formula |
C14H7N3OF6
|
|---|---|
| Molecular Weight |
347.22
|
| Exact Mass |
347.049
|
| CAS # |
1262406-08-5
|
| PubChem CID |
135566520
|
| Appearance |
Typically exists as solid at room temperature
|
| LogP |
4.368
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
1
|
| Heavy Atom Count |
24
|
| Complexity |
544
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1=CC(=CC(=C1)C(F)(F)F)C2=C3C(=CC(=NC3=NN2)O)C(F)(F)F
|
| InChi Key |
YEINPIKXEQEWSU-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C14H7F6N3O/c15-13(16,17)7-3-1-2-6(4-7)11-10-8(14(18,19)20)5-9(24)21-12(10)23-22-11/h1-5H,(H2,21,22,23,24)
|
| Chemical Name |
4-(trifluoromethyl)-3-[3-(trifluoromethyl)phenyl]-2,7-dihydropyrazolo[3,4-b]pyridin-6-one
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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) |
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
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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 | 2.8800 mL | 14.4001 mL | 28.8002 mL | |
| 5 mM | 0.5760 mL | 2.8800 mL | 5.7600 mL | |
| 10 mM | 0.2880 mL | 1.4400 mL | 2.8800 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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