| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 100mg | |||
| Other Sizes |
| Targets |
GSK-3α 0.35 nM (IC50) GSK-3β 0.25 nM (IC50) CDK2 0.22 μM (IC50) CDK5 1.3 μM (IC50)
GSK-3 inhibitor 3 selectively targets glycogen synthase kinase-3 (GSK-3), specifically the α and β isoforms. GSK-3 is a key serine/threonine kinase involved in regulating various cellular processes, including glycogen metabolism, neuronal signaling, and cell cycle regulation. The compound also shows activity against CDK2 (IC50 = 0.22 μM) and CDK5 (IC50 = 1.3 μM), though its primary therapeutic potential lies in GSK-3 inhibition for neurodegenerative diseases. |
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| ln Vitro |
GSK-3 inhibitor 3 (Compound 34) has an IC50 of 1.3 μM for CDK5, and 0.22 μM for CDK2, making it a highly selective inhibitor of both of these proteins [1].
In vitro, GSK-3 inhibitor 3 (Compound 34) demonstrates potent GSK-3 inhibition with IC50s of 0.35 nM for GSK-3α and 0.25 nM for GSK-3β. It shows high selectivity for GSK-3 over CDK2 (IC50 = 0.22 μM) and CDK5 (IC50 = 1.3 μM). At 1 μM concentration, the compound effectively inhibits CDK2 and CDK5 activity. These in vitro characteristics support its use as a highly selective tool for studying GSK-3-mediated signaling pathways in neurological disease models. |
| ln Vivo |
In male C57BL6 mice, GSK-3 inhibitor 3 (Compound 34) (2 mg/kg i.v., 10 mg/kg oral) showed a T1/2 of 2.5 hours (i.v.) and an oral bioavailability (F%) of about. 100 percent[1]. In the triple transgenic mouse Alzheimer's disease model, GSK-3 inhibitor 3 (10 mg/kg, single oral dose) decreases the phosphorylation level of Tau 396 by 33% [1].
In vivo, GSK-3 inhibitor 3 demonstrates significant activity in a triple transgenic mouse model of Alzheimer's disease (LaFerla 3xTg-C57BL6 mice). The compound reduces tau protein phosphorylation at Ser396 with an IC50 of 10 nM. Pharmacokinetic studies in male C57BL6 mice showed a half-life (T1/2) of 2.5 hours following intravenous administration at 2 mg/kg and an oral bioavailability (F%) of approximately 100%. The compound is brain-permeable, supporting its use in central nervous system research. |
| Enzyme Assay |
In vitro enzyme inhibition assays for GSK-3 inhibitor 3 typically involve measuring kinase activity using recombinant GSK-3α and GSK-3β enzymes. The assay is performed in the presence of varying concentrations of the compound and a peptide substrate. Kinase activity is detected using a radioactive (³³P-ATP) or luminescent (ADP-Glo) format, and IC50 values are calculated from dose-response curves. Selectivity profiling against related kinases such as CDK2 and CDK5 is performed using similar assay formats.
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| Cell Assay |
Cellular activity of GSK-3 inhibitor 3 is typically assessed in neuronal cell models or disease-relevant cell lines. The compound is administered at concentrations ranging from nanomolar to micromolar, and its effects on tau phosphorylation are measured by Western blotting using phospho-specific antibodies against tau Ser396. Cell viability and proliferation assays may be performed to assess cytotoxicity. For mechanistic studies, downstream signaling pathways such as Wnt/β-catenin are evaluated using reporter gene assays or Western blot analysis.
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| Animal Protocol |
Animal/Disease Models: Alzheimer's disease model using LaFerla 3xTg-C57BL6 mice[1]
Doses: 10 mg/kg Route of Administration: po (oral gavage) Experimental Results: Produced a 37 % reduction in pTau396. Animal/Disease Models: In male C57BL6 mice. (pharmacokinetic/PK assay)[1] Doses: 2 mg/kg; 10 mg/kg Route of Administration: intravenous (iv)injection; po (oral gavage) Experimental Results: pharmacokinetic/PK parameters for GSK -3 inhibitor 3(Compound 34) in Mice[1] In vivo studies are conducted in the LaFerla 3xTg-C57BL6 triple transgenic mouse model of Alzheimer's disease. GSK-3 inhibitor 3 is administered at 10 mg/kg orally or 2 mg/kg intravenously. After treatment, brain tissue is collected and analyzed for tau phosphorylation at Ser396 using immunoassays. Pharmacokinetic parameters are assessed in male C57BL6 mice following intravenous and oral administration to determine half-life and bioavailability. |
| ADME/Pharmacokinetics |
GSK-3 inhibitor 3 has demonstrated favorable pharmacokinetic properties with oral bioavailability of approximately 100% in male C57BL6 mice. Following intravenous administration at 2 mg/kg, the compound exhibits a half-life (T1/2) of 2.5 hours. The compound is brain-permeable, which is essential for its application in central nervous system research. Its oral activity and high bioavailability make it suitable for chronic dosing studies in neurological disease models.
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| Toxicity/Toxicokinetics |
Toxicological data for GSK-3 inhibitor 3 is primarily derived from in vivo studies in mouse models. In the Alzheimer's disease model studies, the compound was administered at doses up to 10 mg/kg orally without reported significant adverse effects. As with all research compounds, GSK-3 inhibitor 3 is intended for research use only and not for human therapeutic applications. Comprehensive toxicology profiling would be required for clinical development, but such data is not publicly available for this research compound.
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| References | |
| Additional Infomation |
GSK-3 inhibitor 3 is a selective, orally active, brain-penetrant inhibitor with potential therapeutic applications in Alzheimer's disease and other neurodegenerative disorders. By inhibiting GSK-3, the compound reduces tau hyperphosphorylation, a key pathological feature of Alzheimer's disease. It has been studied in the triple transgenic mouse model (LaFerla 3xTg-C57BL6), demonstrating both pharmacodynamic effects (tau phosphorylation reduction) and favorable pharmacokinetic properties. The compound represents a valuable research tool for studying GSK-3 biology and evaluating the therapeutic potential of GSK-3 inhibition.
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| Molecular Formula |
C23H15FN6O
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|---|---|
| Molecular Weight |
410.403207063675
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| Exact Mass |
410.129
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| CAS # |
2227279-84-5
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| PubChem CID |
134556469
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
3.6
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
31
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| Complexity |
637
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC(=CC=C1C#N)NC2=NC=CC(=N2)C(=O)NC3=C(C=CN=C3)C4=CC=C(C=C4)F
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| InChi Key |
QLWFPXXGZGCHFQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H15FN6O/c24-17-5-3-16(4-6-17)19-9-11-26-14-21(19)29-22(31)20-10-12-27-23(30-20)28-18-7-1-15(13-25)2-8-18/h1-12,14H,(H,29,31)(H,27,28,30)
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| Chemical Name |
2-(4-cyanoanilino)-N-[4-(4-fluorophenyl)pyridin-3-yl]pyrimidine-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 : ~50 mg/mL (~121.83 mM)
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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 | 2.4366 mL | 12.1832 mL | 24.3665 mL | |
| 5 mM | 0.4873 mL | 2.4366 mL | 4.8733 mL | |
| 10 mM | 0.2437 mL | 1.2183 mL | 2.4366 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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