| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Targets |
GSK3-IN-1 targets glycogen synthase kinase-3 (GSK-3), a serine/threonine kinase that plays a central role in glycogen metabolism, insulin signaling, Wnt signaling, and cell survival. GSK3-IN-1 inhibits both GSK3α (IC50 = 9.5 nM) and GSK3β (IC50 = 24 nM) isoforms. It also inhibits CDKL5 with an IC50 of 4.6 nM. By inhibiting GSK-3, the compound activates downstream signaling pathways involved in glycogen synthesis and insulin sensitivity, making it relevant for diabetes research.
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| ln Vitro |
In vitro, GSK3-IN-1 shows potent inhibition of GSK-3 activity with an IC50 of 12 µM in standard biochemical assays. In NanoBRET assays, it demonstrates even greater potency with IC50 values of 4.6 nM for CDKL5, 24 nM for GSK3β, and 9.5 nM for GSK3α. The compound's activity against multiple kinases in the GSK-3 family and CDKL5 suggests it may be useful for studying the roles of these kinases in various cellular processes and disease contexts.
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| ln Vivo |
In vivo, GSK3-IN-1 has potential applications in diabetes research. GSK-3 inhibition is known to increase glycogen synthesis and improve insulin sensitivity, which could be beneficial for treating type 2 diabetes. However, specific in vivo efficacy data for GSK3-IN-1 have not been detailed in the available literature. The compound's in vivo effects would depend on its pharmacokinetic properties and ability to achieve sufficient target engagement in relevant tissues.
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| Enzyme Assay |
For in vitro kinase assays, recombinant GSK-3α, GSK-3β, or CDKL5 proteins are incubated with a peptide substrate and ATP in kinase assay buffer. The NanoBRET assay is used to measure target engagement in live cells, where a fluorescent tracer competes with the test compound for binding to the kinase of interest. The test compound is added at various concentrations (typically 0.001-100 µM). BRET signal is measured, and IC50 values are calculated by fitting dose-response curves.
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| Cell Assay |
For cell-based assays, cells are treated with GSK3-IN-1 at concentrations ranging from 0.1-100 µM for various time points. GSK-3 activity can be assessed by measuring the phosphorylation status of GSK-3 substrates such as glycogen synthase or β-catenin by Western blotting. Cellular glycogen content can be measured using colorimetric assays. Cell viability and proliferation can also be assessed in relevant cell lines to evaluate the functional consequences of GSK-3 inhibition.
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| Animal Protocol |
For in vivo studies, animal models of diabetes (such as db/db mice or high-fat diet-induced insulin resistance models) could be used. GSK3-IN-1 would be administered via oral or intraperitoneal routes at doses determined from pharmacokinetic studies. Blood glucose levels, insulin sensitivity (via glucose tolerance tests or insulin tolerance tests), and hepatic glycogen content would be measured to assess the compound's efficacy. However, specific in vivo protocols for GSK3-IN-1 have not been reported.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of GSK3-IN-1 have been partially characterized. The compound is soluble in DMSO at 60 mg/mL. Powder form can be stored at -20°C for 3 years or at 4°C for 2 years. Solutions can be stored at -80°C for 1 year. Further detailed PK parameters including oral bioavailability, half-life, and tissue distribution would be required for in vivo studies. The compound's molecular weight of 303.77 g/mol suggests potential for drug-like properties.
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| Toxicity/Toxicokinetics |
Toxicological data for GSK3-IN-1 have not been reported in the available literature. As a research compound, it is intended for laboratory use only and is not for human or veterinary use. Standard safety precautions should be followed when handling this compound. Comprehensive toxicology studies would be required before any clinical development.
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| References | |
| Additional Infomation |
GSK3-IN-1 (compound 11) is a GSK-3 inhibitor with an IC50 of 12 µM in standard assays and demonstrates potent activity in NanoBRET assays with IC50 values of 4.6 nM (CDKL5), 24 nM (GSK3β), and 9.5 nM (GSK3α). It can be used in diabetes research. The compound inhibits glycogen synthase kinase-3, a key regulator of glycogen metabolism and insulin signaling. GSK3-IN-1 is a research tool and is not approved for clinical use.
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| Molecular Formula |
C14H10N3OSCL
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|---|---|
| Molecular Weight |
303.767
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| Exact Mass |
303.023
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| CAS # |
478482-74-5
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| PubChem CID |
851256
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| Appearance |
White to light yellow solid powder
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| Density |
1.43±0.1 g/cm3(Predicted)
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| Boiling Point |
492.2±55.0 °C(Predicted)
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| Flash Point |
251.5±31.5 °C
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| Vapour Pressure |
0.0±1.2 mmHg at 25°C
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| Index of Refraction |
1.673
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| LogP |
4.1
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
20
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| Complexity |
304
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC=C(C(=C1)CSC2=NN=C(O2)C3=CC=NC=C3)Cl
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| InChi Key |
UMPGWHXDJJYISZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C14H10ClN3OS/c15-12-4-2-1-3-11(12)9-20-14-18-17-13(19-14)10-5-7-16-8-6-10/h1-8H,9H2
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| Chemical Name |
2-[(2-chlorophenyl)methylsulfanyl]-5-pyridin-4-yl-1,3,4-oxadiazole
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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 (~329.20 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 | 3.2920 mL | 16.4598 mL | 32.9196 mL | |
| 5 mM | 0.6584 mL | 3.2920 mL | 6.5839 mL | |
| 10 mM | 0.3292 mL | 1.6460 mL | 3.2920 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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