TWS119

For research use only.

Catalog No.S1590

21 publications

TWS119 Chemical Structure

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.

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Selleck's TWS119 has been cited by 21 publications

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Biological Activity

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.
Targets
GSK-3β [1]
(Cell-free assay)
30 nM
In vitro

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. [1] TWS119 is found to potently induces neuronal differentiation in both mouse embryonal carcinoma and ES cells. [2] 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. [3] 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. [4] 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. [5]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
RAW 264.7 MUTDfZRwfG:6aXPpeJkhSXO|YYm= M4X1SlAuOTByMEDu[{9udA>? M4rUOFI1KGh? MY\pcoR2[2W|IHPlcIwh\GWjdHigbY4h[SCmb4PlJIRmeGWwZHXueEBu[W6wZYK= M4D1WlI1OzNyOEWz

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Immunofluorescence
β-catenin / COX-2 ; 

PubMed: 30618773     


The immunofluorescence staining of β-catenin and COX-2 in the NIH3T3 cells. Scale bars: 50 μm.

30618773
Growth inhibition assay
Cell viability; 

PubMed: 19995556     


Cells were exposed to indicated concentrations of TWS119 for 72 h and viable cells (%) was determined. 

19995556
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. [4]

Protocol

Animal Research:[4]
- Collapse
  • Animal Models: Pmel-1 TCR-transgenic mice and pmel-1 ly5.1 double-transgenic mice and pmel-1 Thy1.1 double-transgenic mice
  • Dosages: 30 mg/kg
  • Administration: Intraperitoneal injection
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 64 mg/mL (201.04 mM)
Water Insoluble
Ethanol Insoluble
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.
30 mg/mL

* 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.

Chemical Information

Molecular Weight 318.33
Formula

C18H14N4O2

CAS No. 601514-19-6
Storage powder
in solvent
Synonyms N/A
Smiles NC1=CC(=CC=C1)C2=CC3=C([NH]2)N=CN=C3OC4=CC=CC(=C4)O

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID