| Size | Price | Stock | Qty |
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| Targets |
IC50: 3.01 μM (GSK-3)[3]
GSK3-IN-3 targets glycogen synthase kinase-3 (GSK-3) with an IC50 of 3.01 μM. Unlike conventional ATP-competitive kinase inhibitors, GSK3-IN-3 is non-ATP and non-substrate competitive, suggesting a distinct binding mechanism. Beyond GSK-3 inhibition, the compound also functions as a mitophagy inducer that promotes parkin-dependent mitochondrial autophagy. This dual activity makes it useful for studying the intersection of kinase signaling and mitochondrial quality control pathways. |
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| ln Vitro |
In U2OS-iMLS cells expressing Parkin, GSK3-IN-3 (VP07) (25 μM; 24 hours) causes mitophagy, albeit in a limited way [1]. U2OS-iMLS-Parkin cells undergo mitochondrial fission and morphological alterations due to GSK3-IN-3 (1.56-25 μM; 24 hours) [1]. In an in vitro cell model of Parkinson's disease using SH-SY5Y cells, GSK3-IN-3 (VP0.7) (5 μM, 10 μM;) demonstrated neuroprotective benefits against 6-OHDA [2].
In vitro, GSK3-IN-3 (VP07) induces mitophagy in Parkin-expressing U2OS-iMLS cells at 25 μM for 24 hours, though with limited potency. At concentrations of 1.56-25 μM for 24 hours, it causes mitochondrial fission and morphological changes in U2OS-iMLS-Parkin cells. The compound exhibits GSK-3 inhibitory activity with an IC50 of 3.01 μM. It also shows neuroprotective effects against 6-OHDA-induced toxicity. These in vitro activities support its use in studies of mitochondrial dysfunction and neurodegeneration. |
| ln Vivo |
In vivo data for GSK3-IN-3 is limited in publicly available sources. As a mitophagy inducer and GSK-3 inhibitor, the compound is expected to have potential applications in animal models of neurodegenerative diseases such as Parkinson's disease, where mitochondrial dysfunction plays a central role. The compound's neuroprotective effects against 6-OHDA in vitro suggest potential in vivo efficacy in models of dopaminergic neuron degeneration. However, specific in vivo pharmacokinetic and efficacy studies have not been widely reported in the literature.
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| Enzyme Assay |
The in vitro GSK-3 inhibition assay for GSK3-IN-3 typically uses recombinant GSK-3 enzyme and a peptide substrate in the presence of varying compound concentrations. Kinase activity is measured using radioactive or luminescent detection methods, and IC50 values are calculated from dose-response curves. The non-ATP competitive nature of the compound can be confirmed by performing the assay at different ATP concentrations. Mitophagy induction is assessed in Parkin-expressing U2OS cells using fluorescence microscopy to monitor mitochondrial localization and autophagosome formation.
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| Cell Assay |
Immunofluorescence[1]
Cell Types: Parkin-expressing U2OS-iMLS cells Tested Concentrations: 1.56 μM, 3.12 μM, 6.25 μM, 12.5 μM, and 25 μM; Incubation Duration: 24 hrs (hours) Experimental Results: Induced a mitochondrial morphology change from a filament-shaped network to a more round-shaped network. Cell Viability Assay[2] Cell Types: SH-SY5Y cells Tested Concentrations: 0.5 μM, 1 μM, 3 μM, 5 μM, and 10 μM Incubation Duration: 16 hrs (hours); with 35 μM 6-OHDA Experimental Results: Inhibited cell growth with an IC50 value of 2.57 μM. Cellular assays for GSK3-IN-3 are conducted in U2OS-iMLS-Parkin cells, which stably express Parkin. Cells are treated with GSK3-IN-3 at concentrations ranging from 1.56 to 25 μM for 24 hours. Mitophagy is assessed by monitoring mitochondrial fragmentation and morphological changes using confocal microscopy. Parkin-dependent mitophagy is confirmed by analyzing the co-localization of mitochondria with autophagosomal markers. Neuroprotective effects are evaluated in 6-OHDA-treated neuronal cell models. |
| Animal Protocol |
In vivo studies for GSK3-IN-3 would typically involve animal models of Parkinson's disease or other neurodegenerative conditions. The compound could be administered via intraperitoneal or oral routes, with dosing regimens determined by pharmacokinetic studies. Efficacy would be assessed by measuring behavioral outcomes, dopaminergic neuron survival, and biochemical markers of mitochondrial function and autophagy. However, specific published in vivo protocols for GSK3-IN-3 are not available in the current literature.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for GSK3-IN-3 is not extensively reported in publicly available sources. The compound has a molecular weight of 429.55 g/mol and is expected to have moderate lipophilicity based on its chemical structure. As a research compound with both GSK-3 inhibitory and mitophagy-inducing activities, its pharmacokinetic properties would need to be characterized for specific in vivo applications. Detailed PK parameters such as half-life, bioavailability, and tissue distribution are not available in the current literature.
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| Toxicity/Toxicokinetics |
Toxicity data for GSK3-IN-3 is limited in publicly available sources. As with all research compounds, GSK3-IN-3 is intended for research use only and not for human therapeutic applications. The compound's neuroprotective effects against 6-OHDA suggest a favorable safety profile in neuronal cells, but comprehensive toxicology studies have not been reported. Standard in vitro cytotoxicity assays and in vivo tolerability studies would be required for a complete toxicity assessment.
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| References |
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| Additional Infomation |
GSK3-IN-3 is a unique research tool that combines GSK-3 inhibition with parkin-dependent mitophagy induction. Its non-ATP competitive mechanism of GSK-3 inhibition distinguishes it from conventional kinase inhibitors. The compound has been studied in the context of neurodegenerative diseases, cancer, and metabolic disorders. Its neuroprotective effects against 6-OHDA suggest potential applications in Parkinson's disease research. GSK3-IN-3 is available as a research compound for studying mitophagy, mitochondrial dynamics, and GSK-3 signaling pathways.
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| Molecular Formula |
C24H35N3O4
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|---|---|
| Molecular Weight |
429.552406549454
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| Exact Mass |
429.262
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| CAS # |
331963-27-0
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| PubChem CID |
54687085
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
6.5
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
31
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| Complexity |
647
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N1(CC)C2=C(C=CC=C2)C(O)=C(C(NNC(=O)CCCCCCCCCCC)=O)C1=O
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| InChi Key |
MHKIYMMTEMNCFE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H35N3O4/c1-3-5-6-7-8-9-10-11-12-17-20(28)25-26-23(30)21-22(29)18-15-13-14-16-19(18)27(4-2)24(21)31/h13-16,29H,3-12,17H2,1-2H3,(H,25,28)(H,26,30)
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| Chemical Name |
N'-dodecanoyl-1-ethyl-4-hydroxy-2-oxoquinoline-3-carbohydrazide
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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 : 4.17 mg/mL (9.71 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 | 2.3280 mL | 11.6401 mL | 23.2802 mL | |
| 5 mM | 0.4656 mL | 2.3280 mL | 4.6560 mL | |
| 10 mM | 0.2328 mL | 1.1640 mL | 2.3280 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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