For research use only.
Molecular Weight(MW): 318.33
TWS119 is a GSK-3β inhibitor with IC50 of 30 nM in a cell-free assay; capable of inducing neuronal differentiation and may be useful to stem cell biology. GSK-3β inhibition triggers autophagy.
Selleck's TWS119 has been cited by 21 publications
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|Description||TWS119 is a GSK-3β inhibitor with IC50 of 30 nM in a cell-free assay; capable of inducing neuronal differentiation and may be useful to stem cell biology. GSK-3β inhibition triggers autophagy.|
Treatment of a monolayer of P19 cells with 1 μM TWS119 causes 30–40% cells to differentiate specifically into neuronal lineages based on counting of TuJ1 positive cells with correct neuronal morphology (up to 60% neuronal differentiation occurred through the standard EB formation protocol with concomitant TWS119 treatment). TWS119 tightly binds to GSK-3β (K D = 126 nM) which is quantified by surface plasmon resonance (SPR) and further demonstrates an IC50 of 30 nM.  TWS119 is found to potently induces neuronal differentiation in both mouse embryonal carcinoma and ES cells.  TWS119 treatment towards hepatic stellate cells (HSC) leads to reduced b-catenin phosphorylation, induces nuclear translocation of b-catenin, elevates glutamine synthetase production, impedes synthesis of smooth muscle actin and Wnt5a, but promotes the expression of glial fibrillary acidic protein, Wnt10b, and paired-like homeodomain transcription factor 2c.  TWS119 triggers a rapid accumulation of β-catenin (mean 6.8 -fold increase by densitometry), augments nuclear protein interaction with oligonucleotide containing the DNA sequences to which Tcf and Lef bind and sharply up-regulates the expression of Tcf7, Lef1 and other Wnt target genes including Jun, Ezd7 (encoding Frizzled-7), Nlk (encoding Nemo-like kinase). TWS119 induces a dose-dependent decrease in T cell-specific killing and IFN-g release associated with the preservation of the ability to produce IL-2.  A recent study indicates Wnt signaling is induced in polyclonally activated human T cells by treatment with TWS119. These T cells preserve a native CD45RA(+)CD62L(+) phenotype compared with control-activated T cells that progresses to a CD45RO(+)CD62L(-) effector phenotype and this occurs in a TWS119 dose-dependent manner. TWS119-induced Wnt signaling reduces T cell expansion as a result of a block in cell division, and impairs acquisition of T cell effector function as measured by degranulation and IFN-γ production in response to T cell activation. The block in T cell division may be attributed to reduced IL-2Rα expression in TWS119-treated T cells that lowers their capacity to use autocrine IL-2 for expansion. 
|In vivo||A cell population that expressed low levels of CD44 and high levels of CD62L on the cell surface when 30 mg/kg of TWS119 is administered. |
-  Ding S, et al, Pro Natl Acad Sci U S A, 2003, 100(13), 7632-7637.
-  Ding S, et al, Nat Biotechnol, 2004, 22(7), 833-840.
-  Kordes C, et al, Biochem Biophys Res Commun, 2008, 367(1), 116-123.
|In vitro||DMSO||64 mg/mL (201.04 mM)|
|In vivo||Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
1% DMSO+30% polyethylene glycol+1% Tween 80
For best results, use promptly after mixing.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
In vivo Formulation Calculator (Clear solution)
|Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)|
|Dosage||mg/kg||Average weight of animals||g||Dosing volume per animal||ul||Number of animals|
|Step 2: Enter the in vivo formulation (Different batches have different solubility ratios, please contact Selleck to provide you with the correct ratio)|
|% DMSO % % Tween 80 % ddH2O|
Working concentration： mg/ml；
Method for preparing DMSO master liquid: ： mg drug pre-dissolved in μL DMSO (Master liquid concentration mg/mL，)
Method for preparing in vivo formulation：Take DMSO master liquid, next addμL PEG300， mix and clarify, next addμL Tween 80，mix and clarify, next add μL ddH2O，mix and clarify.
1.Please make sure the liquid is clear before adding the next solvent.
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