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TWS119

(CAS No:601514-19-6)
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.
CAS No:601514-19-6
Molecular Weight(MW):318.33
Purity:99.00%
Specification:500MG;1G;5G;10G;50G;100G
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QC Documents
 COA  MSDS  HPLC  NMR
ChemicalInfomation
CAS No: 601514-19-6
Molecular formula(MF) C18H14N4O2
Molecular Weight(MW): 318.33
Alias
Solubility
In vitro DMSO 64 mg/mL (201.04 mM)
Water <1 mg/mL
Ethanol <1 mg/mL
In vivo 1% DMSO+30% polyethylene glycol+1% Tween 80 30 mg/mL
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.
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 Cytotoxicity Assay 0-10000ng/ml 24 h induces cell death in a dose dependent manner 24330853

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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]