| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| Other Sizes |
| Targets |
GSK-3β 64 nM (IC50)
GSK-3β inhibitor 8 targets glycogen synthase kinase-3β (GSK-3β) as an effective and selective inhibitor with an IC50 of 64 nM. By inhibiting GSK-3β, it negatively regulates the Wnt signaling pathway. The compound also stimulates β cell proliferation, suggesting potential applications in diabetes research. Its thienopyrimidine scaffold represents a chemical class of GSK-3β inhibitors with distinct binding properties. The compound's mechanism involves ATP-competitive inhibition at the kinase active site. |
|---|---|
| ln Vitro |
GSK-3β inhibitor 8 (Compound 1a) (1 nM-100 μM; 7 d) dose-dependently increases β-cell proliferation with an EC50 value of 1.41 μM. GSK-3β inhibitor 8 (2 μM; 72 h) promotes replicating R7T1 β cells roughly 2-fold [1]. GSK-3β inhibitor 8 (1 nM-100 μM; 24 h) stimulates the activation of Super (8X) TOPFlash reporter with an EC50 value of 1.25 μM[1]. GSK-3β inhibitor 8 (2 μM; 72 h) increases the translocation of β-catenin into the nucleus of HEK293 cells [1].
In vitro, GSK-3β inhibitor 8 (1 nM-100 μM; 7 days) dose-dependently stimulates β cell proliferation with an EC50 of 1.41 μM. At 2 μM for 72 hours, it increases R7T1 β cell replication by approximately 2-fold. The compound is an effective and selective inhibitor of GSK-3β with an IC50 of 64 nM. It negatively regulates the Wnt signaling pathway. These activities make it a valuable tool for studying β cell biology and diabetes. |
| ln Vivo |
In vivo studies of GSK-3β inhibitor 8 are limited in publicly available literature. As a compound that stimulates β cell proliferation, it may have potential for in vivo investigations of diabetes and β cell regeneration. GSK-3β inhibitors have been studied in animal models of diabetes for their effects on glucose homeostasis and β cell mass. However, specific in vivo efficacy data and detailed animal model studies for this compound have not been extensively reported. Further research is needed to establish its in vivo activity profile.
|
| 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 8 in the presence of ATP. Kinase activity is measured by quantifying substrate phosphorylation using radioactive or luminescent methods. IC50 values (64 nM) are calculated from dose-response curves. For β cell proliferation assays, R7T1 β cells or other pancreatic β cell lines are treated with compound and proliferation is measured by cell counting or BrdU incorporation. Assays are performed in triplicate with appropriate vehicle controls.
|
| Cell Assay |
For in vitro cellular assays, pancreatic β cell lines such as R7T1 cells are cultured in appropriate media under standard conditions (37°C, 5% CO2). GSK-3β inhibitor 8 is dissolved in DMSO and diluted in culture medium to desired concentrations (1 nM-100 μM). Cells are treated with compound for specified durations (e.g., 7 days for proliferation assays). β cell proliferation is assessed by cell counting, BrdU incorporation, or Ki67 staining. Wnt signaling activity can be assessed using reporter assays or by measuring β-catenin levels by Western blot. Each concentration is tested in replicate wells with vehicle controls.
|
| Animal Protocol |
For in vivo animal studies of GSK-3β inhibitor 8, no specific published protocols are available. For general in vivo administration of GSK-3β inhibitors in diabetes models, compounds are typically formulated in suitable vehicles and administered via oral gavage, intraperitoneal (i.p.) injection, or subcutaneous (s.c.) injection. Dosing regimens vary by study objective. For β cell proliferation studies, pancreatic tissue may be collected for histological analysis of β cell mass. Blood glucose levels may be monitored. All procedures must follow institutional animal care and use committee guidelines.
|
| ADME/Pharmacokinetics |
Pharmacokinetic properties of GSK-3β inhibitor 8 are characteristic of a small-molecule kinase inhibitor. The compound has a molecular weight of 413.92, formula C20H20ClN5OS, and CAS number 1139875-74-3. Purity: 98.16%. Storage: typically at -20°C for powder; in solvent at -80°C. Solubility: soluble in DMSO and other organic solvents. Specific pharmacokinetic parameters such as half-life, clearance, and bioavailability are not extensively reported in publicly available sources.
|
| Toxicity/Toxicokinetics |
According to available safety information, GSK-3β inhibitor 8 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.
|
| References | |
| Additional Infomation |
GSK-3β inhibitor 8 (GSK3β Inhibitor XVIII) is a thienopyrimidine derivative and effective, selective GSK-3β inhibitor with an IC50 of 64 nM. It negatively regulates Wnt signaling and stimulates β cell proliferation (EC50=1.41 μM). It has a molecular weight of 413.92 and formula C20H20ClN5OS. It is for research use only with no clinical development or regulatory approvals reported.
|
| Molecular Formula |
C20H20CLN5OS
|
|---|---|
| Molecular Weight |
413.92
|
| Exact Mass |
413.107
|
| CAS # |
1139875-74-3
|
| PubChem CID |
46215122
|
| Appearance |
White to off-white solid powder
|
| Density |
1.4±0.1 g/cm3
|
| Boiling Point |
632.3±65.0 °C at 760 mmHg
|
| Flash Point |
336.2±34.3 °C
|
| Vapour Pressure |
0.0±1.9 mmHg at 25°C
|
| Index of Refraction |
1.666
|
| LogP |
3.59
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
28
|
| Complexity |
533
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CN1CCN(CC1)C(=O)C2=C(C=C(C=C2)NC3=NC=CC(=N3)C4=CC=CS4)Cl
|
| InChi Key |
CLDIUVXCUVQLGD-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C20H20ClN5OS/c1-25-8-10-26(11-9-25)19(27)15-5-4-14(13-16(15)21)23-20-22-7-6-17(24-20)18-3-2-12-28-18/h2-7,12-13H,8-11H2,1H3,(H,22,23,24)
|
| Chemical Name |
[2-chloro-4-[(4-thiophen-2-ylpyrimidin-2-yl)amino]phenyl]-(4-methylpiperazin-1-yl)methanone
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| 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 | 2.4159 mL | 12.0796 mL | 24.1593 mL | |
| 5 mM | 0.4832 mL | 2.4159 mL | 4.8319 mL | |
| 10 mM | 0.2416 mL | 1.2080 mL | 2.4159 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
