GNF4877 |
| Catalog No.GC38787 |
GNF4877 est un puissant inhibiteur de DYRK1A et de GSK3β avec des IC50 de 6nM et 16nM, respectivement, ce qui entraÎne le blocage de l'exportation nucléaire du facteur nucléaire des lymphocytes T activés (NFATc) et une augmentation de la prolifération des cellules β (EC50 de 0,66μM pour la souris β (cellules R7T1)).
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 2041073-22-5
Sample solution is provided at 25 µL, 10mM.
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GNF4877 is a potent DYRK1A and GSK3β inhibitor with IC50s of 6 nM and 16 nM, respectively, which leads to blockade of nuclear factor of activated T-cells (NFATc) nuclear export and increased β-cell proliferation (EC50 of 0.66 μM for mouse β (R7T1) cells)[1].
High glucose concentrations and glucokinase activators (GKAs) increase Ca2+ signalling in β-cells, and increase intracellular Ca2+ leads to activation of calcineurin and nuclear translocation of NFATc proteins. Indeed, concentrations of GNF4877 ((0.1 μM, 0.3 μM) well below the EC50 for β-cell proliferation are able to induce proliferation in the presence of high glucose or pharmacological activators of glucokinase. Finally, increasing intracellular Ca2+ with glibenclamide (a sulfonylurea receptor 1 inhibitor) or Bay K8644 (an L-type Ca2+ channel activator) show additive activity with GNF4877[1].
GNF4877 (50 mg/kg; oral gavage; twice a day; for 15 days; double transgenic RIP-DTA male mice) treatment induces β-cell proliferation, increases β-cell mass and insulin content, and improves glycaemic control[1]. Animal Model: Double transgenic RIP-DTA male mice (Tg (Ins 2-rtTA) 2 Efr Tg (teto-DTA) 1 Gfi/J) with Doxycycline (28.8±2.4 g; 82±2 days)[1]
[1]. Shen W, et al. Inhibition of DYRK1A and GSK3β induces human β-cell proliferation. Nat Commun. 2015 Oct 26;6:8372.
| Cas No. | 2041073-22-5 | SDF | |
| Canonical SMILES | O=C([C@H]1CN(C2=C(NC(C3=NC(C4=CC(OC(C)C)=CC=C4F)=CN=C3N)=O)C=NC=C2)CCC1)O | ||
| Formula | C25H27FN6O4 | M.Wt | 494.52 |
| Solubility | DMSO: 4.17 mg/mL (8.43 mM and warming) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.0222 mL | 10.1108 mL | 20.2216 mL |
| 5 mM | 0.4044 mL | 2.0222 mL | 4.0443 mL |
| 10 mM | 0.2022 mL | 1.0111 mL | 2.0222 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
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Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 12 reference(s) in Google Scholar.)
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