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.
Cited by 5 Publications
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Fig.6. TWS119 enhanced the cellular expression of ADRP by inhibiting GSK-3β activity. A: GSK-3β kinase activity was evaluated in HKC cells in the control group and the TWS119-treated group. *Indicates P < 0.05 vs. control group. B: Western blotting analysis was used to clarify the effect of 10 μM TWS119 on SREBP-1 expression (mean values±SD, n = 6). *Indicates P < 0.05 vs. blank control group. C: Immunofluorescence was applied to detect the expression of ADRP in the control and TWS119-treated HKC cells.
Int J Biochem Cell Biol 2013 45(9), 2066-75. TWS119 purchased from Selleck.
Lysates of HCT116p53KO cells were harvested 24 hs after treatment with different GSK3 inhibitors and GSK3A/B activation/inactivation checked by western blot: a mix of pSer21-GSK3A and pSer9-GSK3B antibodies and antibody cross-reacting with both pTyr279-GSK3A and pTyr216-GSK3B were used to assess the specificity of the inhibitor for GSK3A. BIO: 6-bromoindirubin-3'-oxime, TWS: TWS119, SB2: SB216763, SB4: SB415286.
PLoS One 2014 9(7), e100947. TWS119 purchased from Selleck.
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2. For more details, such as half maximal inhibitory concentrations (IC50s) and working concentrations of each inhibitor, please click on the link of the inhibitor of interest.
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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.|
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||1% DMSO+30% polyethylene glycol+1% Tween 80||30 mg/mL|
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