| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
GSK-3β 3.1 nM (IC50)
GSK-3beta inhibitor 22 targets glycogen synthase kinase 3 beta (GSK-3beta), a serine/threonine kinase that plays a critical role in multiple cellular processes, including glycogen metabolism, cell cycle regulation, neuronal signaling, and apoptosis. GSK-3beta is implicated in the pathogenesis of Alzheimer‘s disease, where it contributes to tau hyperphosphorylation and the formation of neurofibrillary tangles. This compound is a potent GSK-3beta inhibitor with an IC₅0 of 3.1 nM, making it a valuable tool for studying GSK-3beta function and for developing potential therapeutics for Alzheimer's disease and other neurodegenerative conditions. |
|---|---|
| ln Vitro |
In vitro, GSK-3beta inhibitor 22 is a potent GSK-3beta inhibitor with an IC₅0 of 3.1 nM. It shows selectivity for GSK-3beta over other kinases, making it a useful chemical probe for studying GSK-3beta signaling pathways. The compound can be used to reduce tau phosphorylation in neuronal cell cultures. It has potential for use in research focused on Alzheimer‘s disease (AD) and other neurodegenerative diseases. Specific cellular activity data (e.g., IC₅0 for tau phosphorylation) is not provided, but the compound is described as having high potency and selectivity.
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| ln Vivo |
GSK-3beta inhibitor 22 has the potential to study Alzheimer‘s disease (AD) in vivo. As a potent GSK-3beta inhibitor (IC₅0 = 3.1 nM), it could be used to evaluate the effects of GSK-3beta inhibition on tau pathology, neuroinflammation, and cognitive function in animal models of AD, such as the 3xTg-AD or APP/PS1 transgenic mouse models. No specific in vivo efficacy data is provided. The compound is a research-grade chemical and is not an approved drug.
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| Enzyme Assay |
In vitro GSK-3beta kinase inhibition assay: The activity of recombinant human GSK-3beta is measured using a radiometric or fluorescence-based assay. GSK-3beta (0.5-1 nM) is incubated in kinase buffer (20 mM HEPES pH 7.5, 10 mM MgCl2, 1 mM DTT, 0.01% Triton X-100) with 10 uM ATP (including 0.5 uCi [gamma-32P]-ATP) and a specific peptide substrate (e.g., pre-phosphorylated GS-1 peptide, 50-100 uM). GSK-3beta inhibitor 22 (0.001-1000 nM) is added, and the reaction is incubated at 30degC for 30-60 min. The phosphorylated peptide is spotted onto P81 phosphocellulose filters, washed, and counted. IC₅0 (3.1 nM) is calculated.
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| Cell Assay |
For cell-based studies, SH-SY5Y neuroblastoma cells or primary cortical neurons are seeded in 6-well plates (3×10⁵ cells/well) and differentiated with retinoic acid (10 uM) for 5-7 days. GSK-3beta inhibitor 22 (0.1-1000 nM) is added for 24-48 h. The levels of phospho-tau (Ser396, Ser404, Thr231) are measured by Western blotting. Total tau is used as a loading control. Cell viability is assessed by MTT assay. The compound is expected to reduce tau phosphorylation in a concentration-dependent manner.
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| Animal Protocol |
In vivo efficacy can be evaluated in the 3xTg-AD mouse model of Alzheimer‘s disease. Female 3xTg-AD mice (6-8 months old, n=10-12/group) are administered GSK-3beta inhibitor 22 formulated in 10% DMSO + 40% PEG300 + 5% Tween 80 + 45% saline, administered intraperitoneally (IP) at doses of 1-10 mg/kg once daily for 4-8 weeks. Control groups receive vehicle alone. Cognitive function is assessed by Morris water maze and novel object recognition. At endpoint, brain tissues (hippocampus, cortex) are harvested for Western blotting (phospho-tau, total tau, GSK-3beta) and immunohistochemistry (AT8 for phospho-tau, Iba-1 for microglia, GFAP for astrocytes). No specific data is available.
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| ADME/Pharmacokinetics |
No specific PK data for GSK-3beta inhibitor 22 is available. As a small molecule (MW 423.43), it is expected to have good cell permeability and moderate oral bioavailability. Solubility: DMSO ~100 mg/mL (~236.17 mM, with ultrasonication). For in vivo studies, it can be formulated in 10% DMSO + 40% PEG300 + 5% Tween 80 + 45% saline or in 10% DMSO + 90% Corn oil. The half-life in rodents is expected to be 2-6 hours. For research use, it is stored as a powder at -20degC for 3 years, 4degC for 2 years; in solvent at -80degC for 6 months, -20degC for 1 month.
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| Toxicity/Toxicokinetics |
For GSK-3beta inhibitor 22, hazard statements: H315 (Causes skin irritation), H319 (Causes serious eye irritation), H335 (May cause respiratory irritation). Signal word: Warning. Precautionary statements: P261 (Avoid breathing dust/fume/gas/mist/vapors/spray), P280 (Wear protective gloves/protective clothing/eye protection/face protection), P305+P351+P338 (IF IN EYES: Rinse cautiously with water for several minutes). Storage: at -20degC, sealed, protect from light.
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| References | |
| Additional Infomation |
GSK-3beta inhibitor 22 (compound 20o; CAS# 1005199-84-7) is a research-grade potent and selective GSK-3beta inhibitor (IC₅0 = 3.1 nM). It is not an FDA-approved drug. It is used to study GSK-3beta signaling, tau phosphorylation, and Alzheimer‘s disease. For research use only, not for diagnostic or therapeutic applications.
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| Molecular Formula |
C18H12F3N3O2S2
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|---|---|
| Molecular Weight |
423.43
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| CAS # |
1005199-84-7
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| Appearance |
White to yellow solid powder
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| SMILES |
S(C1=NN=C(C2C=CC3=C(C=2)SC=N3)O1)CC1=CC=C(C(C(F)(F)F)=C1)OC
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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 (~236.17 mM; with ultrasonication)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.90 mM)(saturation unknown) in 10% DMSO 40% PEG300 5% Tween-80 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 and add it to 400 μL PEG300, mix well; then add 50 μL Tween-80 to the above system, mix well; then continue to add 450 μL of normal saline to make up to 1 mL. Preparation of normal saline: Dissolve 0.9 g of sodium chloride in ddH₂O and make up to 100 mL to obtain a clear and transparent normal saline solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.90 mM)(saturation unknown) in 10% DMSO 90% Corn Oil (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 and add it to 900 μL corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3617 mL | 11.8083 mL | 23.6167 mL | |
| 5 mM | 0.4723 mL | 2.3617 mL | 4.7233 mL | |
| 10 mM | 0.2362 mL | 1.1808 mL | 2.3617 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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