| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
GSK-3α 10 nM (IC50) GSK-3β 9 nM (IC50)
PF-04802367 targets glycogen synthase kinase-3 (GSK-3) isoforms α and β as a highly selective, ATP-competitive inhibitor. It has an IC50 of 2.1 nM based on a recombinant human GSK-3β enzyme assay and 1.1 nM based on ADP-Glo assay. The compound exhibits remarkable kinase selectivity, making it a valuable tool for studying GSK-3-mediated signaling pathways. Its mechanism involves ATP-competitive inhibition at the kinase active site, and it has been shown to modulate phosphorylated tau levels in vivo. |
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| ln Vitro |
PF-04802367 (PF-367) is efficient at inhibiting GSK-3β enzymatic activity in vitro with ligand and lipophilic efficiency scores of 0.46 and 7.0, respectively[1]. PF-367 exhibits reasonable in vitro stability in human hepatic microsomes (t1/ 2=78.7 min), has excellent passive permeability[1]. In a stable inducible CHO cell line over-expressing GSK-3β and its substrate tau, PF-367 reduced phosphorylation of tau with an IC50 of 466 nM[1]. PF -367 has good cell survival (IC50 of 117 μM in THLE cytotoxicity experiments) and an IC50 >100 μM in a hERG screening assay[1]. PF-367 demonstrates significant right shifts against β-catenin translocation in HeLa cells with EC50 of 6.2 μM, gene transcription in U20S cells with EC50 of 20.6 μM, and cell proliferation in HeLa cells as determined by Ki-67 incorporation with EC50 of 9.0 μM[1].
In vitro, PF-04802367 is a highly selective GSK-3 inhibitor with an IC50 of 2.1 nM based on a recombinant human GSK-3β enzyme assay and 1.1 nM based on ADP-Glo assay. It is an oxazole-4-carboxamide derivative that functions as a highly potent, ATP-competitive inhibitor of GSK-3 isoforms α and β. The compound exhibits remarkable kinase selectivity. Detailed in vitro characterization data, including kinase selectivity profiling against a panel of kinases and cellular activity assays, are available in the primary literature. |
| ln Vivo |
PF-04802367, also known as PF-367, is a strong GSK-3 inhibitor that exhibits remarkable kinome selectivity and phosphorylated tau level modulation in vivo. A single subcutaneous dose of 1, 3.2, 10, 32, or 50 mg/kg of PF-367 inhibits the phosphorylation of tau in the brain in a dose-dependent manner[1]. A powerful type-I dual GSK-3α/β inhibitor, PF-04802367 (PF-367) exhibits strong in vivo suppression of muscle phosphorylated glycogen synthase (pGS) and robust CNS/peripheral p-Tau absorption, distribution, metabolism, and elimination (ADME) properties[2].
In vivo, PF-04802367 (PF-367) is a strong GSK-3 inhibitor that exhibits remarkable kinase selectivity and modulates phosphorylated tau levels in vivo. A single subcutaneous dose has been shown to produce effects. The compound's ability to modulate phosphorylated tau levels suggests potential applications in neurodegenerative disease research, particularly in tauopathies such as Alzheimer's disease. Specific in vivo efficacy data and detailed animal model studies are available in the primary literature. Further research is ongoing to characterize its full therapeutic potential. |
| Enzyme Assay |
For GSK-3β kinase activity assays, recombinant human GSK-3β enzyme is incubated with appropriate peptide substrates and varying concentrations of PF-04802367 in the presence of ATP. Kinase activity is measured by quantifying substrate phosphorylation using radioactive [γ-33P]-ATP or by luminescent ADP-Glo assays. IC50 values (2.1 nM for enzyme assay, 1.1 nM for ADP-Glo assay) are calculated from dose-response curves. For selectivity profiling, similar assays are performed with a panel of kinases. Assays are performed in triplicate with appropriate vehicle controls and reference inhibitors as positive controls.
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| Cell Assay |
For in vitro cellular assays, cell lines of interest are cultured in appropriate media under standard conditions (37°C, 5% CO2). PF-04802367 is dissolved in DMSO and diluted in culture medium to desired concentrations. Cells are treated with compound for specified durations. GSK-3 activity is assessed by measuring phosphorylation levels of GSK-3 substrates such as tau protein or glycogen synthase by Western blot. Cell viability and proliferation can be assessed using MTT or CCK-8 assays. Each concentration is tested in replicate wells with vehicle controls.
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| Animal Protocol |
Animal/Disease Models: SD (Sprague-Dawley) rats[1]
Doses: 1, 3.2, 10, 32 or 50 mg/kg Route of Administration: A single subcutaneous (sc) Experimental Results: Inhibition of phosphorylation of tau in brain is dose-dependent. For in vivo animal studies, PF-04802367 is typically formulated in suitable vehicles and administered via subcutaneous (s.c.) injection. A single subcutaneous dose has been shown to produce effects on phosphorylated tau levels. Dosing regimens vary by study objective. For tauopathy models, animals may be treated with compound and tau phosphorylation levels are assessed in brain tissue. Blood and tissue samples may be collected for pharmacokinetic analysis. All procedures must follow institutional animal care and use committee guidelines. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of PF-04802367 are characteristic of a small-molecule kinase inhibitor. The compound has a molecular weight of 361.78, formula C16H16ClN5O3, and CAS number 1962178-27-3. Purity: ≥98.5%. Appearance: solid. Storage: powder at -20°C for 3 years; at 4°C for 2 years; in solvent at -80°C for 6 months or -20°C for 1 month. Solubility: DMSO 90 mg/mL with ultrasonic. Specific pharmacokinetic parameters such as half-life, clearance, and bioavailability are reported in the primary literature.
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| Toxicity/Toxicokinetics |
According to available safety information, PF-04802367 is intended for research purposes only and is not for human use. Standard laboratory safety precautions should be followed when handling this compound, including the use of appropriate personal protective equipment (gloves, lab coat, safety goggles). The compound should be handled in a well-ventilated area. Avoid dust formation and inhalation. In case of skin contact, wash with plenty of soap and water. In case of eye contact, rinse cautiously with water for several minutes. No clinical toxicity data are available.
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| References |
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| Additional Infomation |
PF-04802367 (PF-367) is a highly selective, ATP-competitive GSK-3 inhibitor with IC50 values of 2.1 nM (enzyme assay) and 1.1 nM (ADP-Glo assay). It has a molecular weight of 361.78 and formula C16H16ClN5O3. The compound modulates phosphorylated tau levels in vivo and exhibits remarkable kinase selectivity. It is for research use only with no clinical development or regulatory approvals reported.
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| Molecular Formula |
C16H16CLN5O3
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|---|---|
| Molecular Weight |
361.782941818237
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| Exact Mass |
361.094
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| CAS # |
1962178-27-3
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| PubChem CID |
60148521
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| Appearance |
White to light yellow solid powder
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| LogP |
2.3
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
25
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| Complexity |
444
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1=C(C=CC(=C1)C1=C(C(NCCCN2C=NC=N2)=O)N=CO1)OC
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| InChi Key |
RQFYFNAGNBUGFC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H16ClN5O3/c1-24-13-4-3-11(7-12(13)17)15-14(20-10-25-15)16(23)19-5-2-6-22-9-18-8-21-22/h3-4,7-10H,2,5-6H2,1H3,(H,19,23)
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| Chemical Name |
5-(3-chloro-4-methoxyphenyl)-N-[3-(1,2,4-triazol-1-yl)propyl]-1,3-oxazole-4-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: 100 mg/mL (276.41 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.91 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 (6.91 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 (6.91 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 | 2.7641 mL | 13.8206 mL | 27.6411 mL | |
| 5 mM | 0.5528 mL | 2.7641 mL | 5.5282 mL | |
| 10 mM | 0.2764 mL | 1.3821 mL | 2.7641 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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