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    InvivoChem Cat #: V0214
    CAS #: 601514-19-6 Purity ≥98%

    Description: TWS119, a pyrrolopyrimidine compound, is a novel, potent and selective/specific GSK-3β (Glycogen synthase kinase-3β) inhibitor with potential usefulness for in vivo stem cell biology and therapy. It inhibits GSK-3β with an IC50 of 30 nM in a cell-free assay; it is capable of inducing neuronal differentiation and may be useful to stem cell biology. It is screened out from a library of pyrrolopyrimidines as a molecule that selectively induces neuronal differentiation when using mouse P19 EC cells. TWS119 binds to GSK-3β tightly with a Kd value of 126nM. The combination of TWS119 and GSK-3β modulates the activity of the complex and triggers downstream transcriptional events lead the neuronal induction. Besides that, TWS119 promotes neuronal differentiation of mESCs through another mechanism but not the canonical Wnt signaling pathway.

    References:Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7632-7; Nat Biotechnol. 2004 Jul;22(7):833-40.

    Related CAS: 1507095-58-0 (2 TFA salt)  

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    Molecular Weight (MW)




    CAS No.

    601514-19-6 (free base);


    -20℃ for 3 years in powder form

    -80℃ for 2 years in solvent

    Solubility (In vitro)

    DMSO: 64 mg/mL (201.0 mM)

    Water: <1 mg/mL

    Ethanol: <1 mg/mL

    Solubility (In vivo)

    1% DMSO+30% polyethylene glycol+1% Tween 80: 30mg/mL


    TWS-119; TWS 119; TWS119

    Chemical Name: 3-((6-(3-aminophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)oxy)phenol


    InChi Code: InChI=1S/C18H14N4O2/c19-12-4-1-3-11(7-12)16-9-15-17(22-16)20-10-21-18(15)24-14-6-2-5-13(23)8-14/h1-10,23H,19H2,(H,20,21,22)

    SMILES Code: OC1=CC=CC(OC2=C3C(NC(C4=CC=CC(N)=C4)=C3)=NC=N2)=C1

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    In Vitro

    In vitro activity: 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.


    Kinase Assay: TWS119 is a specific inhibitor of GSK-3β, with an IC50 of 30 nM, and activates the wnt/β-catenin pathway.


    Cell Assay: PBMCs are cultured with pamidronate disodium for 8 days and then cells are labelled with or without 1.5 μM carboxyfluorescein succinimidyl ester (CFSE) and CFSE-labelled cells are then seeded in 6-well plates (2.5 × 106 cells/well) followed by treatment with various concentrations of TWS119 for 72 h. The total number of cultured cells is evaluated using an automated cell counter and the γδT cell proliferation is examined by flow cytometry.

    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.

    Animal model

    Pmel-1 TCR-transgenic mice and pmel-1 ly5.1 double-transgenic mice and pmel-1 Thy1.1 double-transgenic mice

    Formulation & Dosage

    Dissolved in DMSO; 30 mg/kg; i.p.


    JNat Med. 2009 Jul;15(7):808-13; Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7632-7; Nat Biotechnol. 2004 Jul;22(7):833-40.  

    These protocols are for reference only. InvivoChem does not independently validate these methods.


    TWS119 activates Wnt signaling in CD8+ T cells. Nat Med. 2009 Jul;15(7):808-13.


    Wnt signaling inhibits CD8+ T cell proliferation and effector differentiation


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