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| Targets |
GSK-3β 6.6 μM (IC50)
GSK-3β inhibitor 3 targets glycogen synthase kinase 3β (GSK-3β) as a potent, selective, irreversible, and covalent inhibitor with an IC50 of 6.6 μM. The compound's covalent and irreversible mechanism of action distinguishes it from reversible GSK-3β inhibitors, allowing for sustained inhibition of the target enzyme. This makes it a valuable tool for studying the long-term effects of GSK-3β inhibition on cellular processes including metabolism, cell differentiation, and apoptosis. Its selectivity for GSK-3β over other kinases has been characterized. |
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| ln Vitro |
GSK-3β inhibitor 3 (compound 4-3) (100 μM) reduces GSK-3α activity by 87.3%[1]. GSK-3β inhibitor 3 (6.25-100 μM; 24-48 h) dose-dependently suppresses the proliferation of NB4 and NB4-R1 cells[1]. GSK-3β inhibitor 3 (12.5-100 μM; 24 h) dramatically enhances the proportion of apoptosis in a dose-dependent way in NB4 and NB4-R1 cells[1].
In vitro, GSK-3β inhibitor 3 is a potent, selective, irreversible, and covalent inhibitor of GSK-3β with an IC50 of 6.6 μM. Its covalent mechanism of action provides sustained inhibition of the target enzyme. The compound can be used for the research of acute promyelocytic leukemia, suggesting activity in cancer cell models. Detailed in vitro characterization data, including enzyme inhibition kinetics and selectivity profiling against a panel of kinases, are available in the primary literature. The compound's covalent nature requires careful consideration in assay design. |
| ln Vivo |
GSK-3β inhibitor 3 (compound 4-3) (15 mg/kg/d; intraperitoneal; 2 weeks) suppresses the growth of tumors in mice by 75.97% as compared to the vehicle control[1]. AUClast=3503.42 ng/mL·h, maximum concentration (Cmax=515 ng/mL), and a lengthy T1/2 of 14.2 h are all displayed by GSK-3β inhibitor 3 (15 mg/kg; a single ip) in mice[1].
In vivo studies of GSK-3β inhibitor 3 are limited in publicly available literature. The compound can be used for the research of acute promyelocytic leukemia, suggesting potential applications in animal models of this disease. As a covalent and irreversible GSK-3β inhibitor, it may provide sustained target engagement in vivo. However, specific in vivo efficacy data and detailed animal model studies have not been extensively reported. Further research is needed to establish its in vivo activity profile, pharmacokinetic properties, and therapeutic potential. |
| Enzyme Assay |
For GSK-3β kinase activity assays, recombinant human GSK-3β enzyme is incubated with appropriate peptide substrates and varying concentrations of GSK-3β inhibitor 3 in the presence of ATP. Kinase activity is measured by quantifying substrate phosphorylation using radioactive [γ-33P]-ATP or by luminescent ADP-Glo assays. IC50 values (6.6 μM) are calculated from dose-response curves. Due to the covalent and irreversible nature of the inhibitor, pre-incubation of enzyme with compound may be performed to assess time-dependent inhibition. Assays are performed in triplicate with appropriate vehicle controls and reference inhibitors as positive controls.
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| Cell Assay |
Cell Viability Assay [1]
Cell Types: NB4 and NB4-R1 cells Tested Concentrations: 6.25, 12.5, 25, 50, 100 μM Incubation Duration: 24, 48 hrs (hours) Experimental Results: Inhibited the cell viability, with IC50s of 19.56 μM and 26.42 μM in NB4 and NB4 -R1 cells at 24 h, respectively. Had little cytotoxicity on human normal liver cells (LO2) and human umbilical vein endothelial cells (HUVECs). Apoptosis Analysis[1] Cell Types: NB4 and NB4-R1 cells Tested Concentrations: 12.5, 25, 50, 100 μM Incubation Duration: 24 hrs (hours) Experimental Results: Induced cell apoptosis. For in vitro cellular assays, leukemia cell lines or other relevant cancer cells are cultured in appropriate media under standard conditions (37°C, 5% CO2). GSK-3β inhibitor 3 is dissolved in DMSO and diluted in culture medium to desired concentrations. Cells are treated with compound for specified durations. GSK-3β activity is assessed by measuring phosphorylation levels of GSK-3β substrates by Western blot. Cell viability, proliferation, and apoptosis are assessed using MTT, flow cytometry, or caspase activity assays. Each concentration is tested in replicate wells with vehicle controls. |
| Animal Protocol |
Animal/Disease Models: Balb/ c female nude mice were injected leukemia cells[1]
Doses: 15 mg/kg/d Route of Administration: Ip for 2 weeks Experimental Results: Inhibited localized growth in NB4 cells. Had mild weight loss compared with control. Animal/Disease Models: Male ICR mice (30 g)[1] Doses: 15 mg/kg (pharmacokinetic/PK Analysis) Route of Administration: A single ip Experimental Results: T1/2=14.2 h; AUClast=3503.42 ng/mL·h; Cmax=515 ng/mL. For in vivo animal studies of GSK-3β inhibitor 3, no specific published protocols are available. For general in vivo administration of covalent kinase inhibitors, compounds are typically formulated in suitable vehicles and administered via oral gavage, intraperitoneal (i.p.) injection, or intravenous (i.v.) injection. Dosing regimens vary by study objective. For acute promyelocytic leukemia models, tumor growth and survival may be monitored. Blood and tissue samples may be collected for pharmacokinetic and pharmacodynamic analysis. All procedures must follow institutional animal care and use committee guidelines. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of GSK-3β inhibitor 3 are characteristic of a small-molecule covalent kinase inhibitor. The compound has a molecular weight of 327.37, formula C18H14FNO2S, and CAS number 1448990-73-5. Purity: ≥98.0%. Appearance: solid. Storage: powder at -20°C for 3 years; at 4°C for 2 years; in solvent at -80°C for 6 months or -20°C for 1 month. Solubility: DMSO 150 mg/mL with ultrasonic. Stability and solubility advice: information concerning product stability, particularly in solution, has rarely been reported.
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| Toxicity/Toxicokinetics |
According to available safety information, GSK-3β inhibitor 3 is intended for research purposes only and is not for human use. Standard laboratory safety precautions should be followed when handling this compound, including the use of appropriate personal protective equipment (gloves, lab coat, safety goggles). The compound should be handled in a well-ventilated area. Avoid dust formation and inhalation. In case of skin contact, wash with plenty of soap and water. In case of eye contact, rinse cautiously with water for several minutes. No clinical toxicity data are available.
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| References | |
| Additional Infomation |
GSK-3β inhibitor 3 is a potent, selective, irreversible, and covalent GSK-3β inhibitor with an IC50 of 6.6 μM. It has a molecular weight of 327.37 and formula C18H14FNO2S. The compound can be used for research of acute promyelocytic leukemia. It is for research use only with no clinical development or regulatory approvals reported.
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| Molecular Formula |
C18H14FNO2S
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|---|---|
| Molecular Weight |
327.37
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| Exact Mass |
327.072
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| CAS # |
1448990-73-5
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| PubChem CID |
155925848
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| Appearance |
White to off-white solid powder
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| LogP |
3.5
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
23
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| Complexity |
476
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N1(C(CC(SC2=CC=CC=C12)C1=CC=C(F)C=C1)=O)C(C=C)=O
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| InChi Key |
DJUQPBPAHPCBBX-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H14FNO2S/c1-2-17(21)20-14-5-3-4-6-15(14)23-16(11-18(20)22)12-7-9-13(19)10-8-12/h2-10,16H,1,11H2
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| Chemical Name |
2-(4-fluorophenyl)-5-prop-2-enoyl-2,3-dihydro-1,5-benzothiazepin-4-one
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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: 250 mg/mL (763.66 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.35 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 20.8 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. Solubility in Formulation 2: ≥ 2.08 mg/mL (6.35 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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0546 mL | 15.2732 mL | 30.5465 mL | |
| 5 mM | 0.6109 mL | 3.0546 mL | 6.1093 mL | |
| 10 mM | 0.3055 mL | 1.5273 mL | 3.0546 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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