Size | Price | Stock | Qty |
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1mg |
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5mg |
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10mg |
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Other Sizes |
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Targets |
GSK-3α 10 nM (IC50) GSK-3β 9 nM (IC50)
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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].
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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].
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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. |
References |
[1]. Steven H Liang, et al. Discovery of a Highly Selective Glycogen Synthase Kinase-3 Inhibitor (PF-04802367) That Modulates Tau Phosphorylation in the Brain: Translation for PET Neuroimaging. Angew Chem Int Ed Engl. 2016 Aug 8;55(33):9601-5.
[2]. Vadim Bernard-Gauthier, et al. Structural Basis for Achieving GSK-3β Inhibition with High Potency, Selectivity, and Brain Exposure for Positron Emission Tomography Imaging and Drug Discovery. J Med Chem. 2019 Nov 14;62(21):9600-9617. |
Molecular Formula |
C16H16CLN5O3
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Molecular Weight |
361.78
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CAS # |
1962178-27-3
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SMILES |
ClC1=C(C=CC(=C1)C1=C(C(NCCCN2C=NC=N2)=O)N=CO1)OC
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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.