| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
p38 mitogen-activated protein kinase (MAPK), specifically the p38alpha and p38beta isoforms. FR 167653 is an orally active and selective inhibitor of p38 MAPK. It is a potent suppressor of TNF-alpha and IL-1beta production via specific inhibition of p38 MAPK activity. By inhibiting p38 MAPK, FR-167653 reduces the production of pro-inflammatory cytokines and helps prevent tissue damage in models of inflammatory diseases.
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| ln Vitro |
In vitro, FR 167653 functions as a potent inhibitor of p38 MAPK, suppressing the production of pro-inflammatory cytokines TNF-alpha and IL-1beta. The compound has been investigated for its potential to mitigate fibrosis in various organ systems, including the liver and lungs. It is used as a research tool to study the role of p38 MAPK in inflammation, fibrosis, and other disease processes. Its anti-inflammatory and anti-fibrotic properties have been demonstrated in various in vitro models.
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| ln Vivo |
Acute tubular necrosis is considerably lessened by FR 167653 (FR 167653 sulfate) (32 mg/kg; ih; 24-48 hours) [1].
In vivo, FR 167653 has been shown to be effective in treating inflammation, relieving trauma, and ameliorating ischemia-reperfusion injury. It suppresses the development of endometriosis in a murine model and ameliorates murine bleomycin-induced pulmonary fibrosis. The compound has demonstrated efficacy in reducing inflammation and protecting various organs, including the kidney and heart, from ischemia-reperfusion injury. It has also shown salutary effects on liver cirrhosis through downregulation of Runx2. |
| Enzyme Assay |
In vitro p38 MAPK inhibition assays for FR 167653 measure inhibition of p38 MAPK kinase activity. The assay uses recombinant human p38 MAPK and a peptide substrate (e.g., ATF-2 or MBP) in the presence of ATP. The compound is serially diluted in assay buffer and pre-incubated with the enzyme for 15-30 minutes. The reaction is initiated by adding ATP and substrate, and after incubation, phosphorylation is detected using either radiometric (33P-ATP) or non-radiometric (HTRF, AlphaScreen, or ELISA) methods. IC50 values are calculated from dose-response curves.
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| Cell Assay |
In vitro cell-based assays for FR 167653 use immune cells (macrophages, monocytes) or other cell types stimulated with inflammatory stimuli (e.g., LPS). Cells are cultured in appropriate media and treated with varying concentrations of the compound (typically 0.1-10 microM) for 1-6 hours prior to stimulation. Cytokine production (TNF-alpha, IL-1beta, IL-6) is measured by ELISA or multiplex assays. p38 MAPK phosphorylation is assessed by Western blotting using phospho-specific antibodies.
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| Animal Protocol |
Animal/Disease Models: Inbred male Balbuc mice (8 weeks old) [1]
Doses: 32 kg/mg Route of Administration: subcutaneous injection; 24-48 hrs (hrs (hours)) Experimental Results: 24 hrs (hrs (hours)) and 48 hrs (hrs (hours)) after ischemia-reperfusion, FR- Acute tubular necrosis scores in the cortex and outer medulla of 167653-treated mice were Dramatically lower than those of vehicle-treated mice. In vivo animal studies for FR 167653 are conducted in various rodent models of inflammation and fibrosis. Common models include LPS-induced endotoxemia, carrageenan-induced paw edema, bleomycin-induced pulmonary fibrosis, and liver cirrhosis models. Animals are administered the compound orally or intraperitoneally at doses of 1-30 mg/kg, either prophylactically or therapeutically. Inflammatory parameters measured include cytokine levels in plasma or tissue homogenates, histological evaluation of tissue inflammation, and organ function tests. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of FR 167653 are characteristic of orally active small-molecule kinase inhibitors. With a molecular weight of 525.51 and a molecular formula of C24H20FN5O6S, the compound is orally active. It is stored as a powder at -20degC. Standard pharmacokinetic parameters (Cmax, Tmax, AUC, oral bioavailability) have been determined in preclinical species. The compound is soluble in DMSO.
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| Toxicity/Toxicokinetics |
FR 167653 is intended for research use only and is not for human therapeutic use. Standard safety precautions for handling chemical compounds apply. The compound is not approved for clinical use.
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| References |
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| Additional Infomation |
FR 167653 is a research-grade selective p38 MAPK inhibitor with anti-inflammatory and anti-fibrotic properties. It has a molecular formula of C24H20FN5O6S and a molecular weight of 525.51. The compound specifically targets the p38alpha and p38beta isoforms and is a potent suppressor of TNF-alpha and IL-1beta production. It is used as a research tool to study the role of p38 MAPK in inflammation, fibrosis, and other disease processes. Not approved for clinical use.
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| Molecular Formula |
C24H18N5O2F.H2O4S
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|---|---|
| Molecular Weight |
525.5089
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| Exact Mass |
525.112
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| CAS # |
158876-66-5
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| Related CAS # |
FR 167653 free base;158876-65-4
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| PubChem CID |
135484078
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| Appearance |
Light yellow to yellow solid powder
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| Boiling Point |
724.4ºC at 760 mmHg
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| Flash Point |
391.9ºC
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| Vapour Pressure |
5.03E-22mmHg at 25°C
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| LogP |
4.307
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
37
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| Complexity |
755
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
KCPHXRBKBLJJJJ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H18FN5O2.H2O4S/c25-19-8-6-17(7-9-19)21-20(16-10-12-26-13-11-16)23-28-30(15-14-29(23)27-21)24(32)22(31)18-4-2-1-3-5-18;1-5(2,3)4/h1-13,28H,14-15H2;(H2,1,2,3,4)
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| Chemical Name |
1-[7-(4-fluorophenyl)-8-pyridin-4-yl-3,4-dihydro-1H-pyrazolo[5,1-c][1,2,4]triazin-2-yl]-2-phenylethane-1,2-dione;sulfuric acid
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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 : ~100 mg/mL (~190.29 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.76 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 25.0 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: ≥ 2.5 mg/mL (4.76 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 25.0 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: ≥ 2.5 mg/mL (4.76 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 | 1.9029 mL | 9.5146 mL | 19.0291 mL | |
| 5 mM | 0.3806 mL | 1.9029 mL | 3.8058 mL | |
| 10 mM | 0.1903 mL | 0.9515 mL | 1.9029 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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