Catalog No.S1590

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.

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TWS119 Chemical Structure

TWS119 Chemical Structure
Molecular Weight: 318.33

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Product Description

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)
IC50 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 LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
RAW 264.7NETlRo5EgXSxdH;4bYNqfHliQYPzZZk>NHjwbm0xNTFyMECwcocwdWx?NXPJPZVOOjRiaB?=M{PGWolv\HWlZYOgZ4VtdCCmZXH0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldi=>M4qwTFI1OzNyOEWz

... Click to View More Cell Line Experimental Data

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(Only for Reference)

Kinase Assay: [1]

Surface Plasmon Resonance (SPR) SPR measurement sare performed on a BIAcore S51 instrument at 25 °C in PBS buffer. Relative light units (11,000–17,000) of a GSK-3β-GST fusion protein are immobilized on S series CM5 biosensor chips by EDC [1-ethyl-3-(3-dimethylaminopropyl)carbodiimide] coupling procedures. Briefly, GSK-3βis diluted into mildly acidic buffer (10 mM KAc, pH 5.0) and injected for 7 minutes at concentrations of 20–200 μg/ml onto a sensor chip previously activated by a 7-min incubation with a 1:1 mixture of EDC (0.2 M) and N-hydroxysuccinimide (NHS, 0.05 M). Finally, unreacted sites of the biosensor matrix are blocked by a 7-min injection of ethanolamine (1 M, pH 8.5). Subsequently, TWS119 is injected for 90 seconds at increasing concentrations (0, 2, 4, 8, 16, 32, 62.5, 125, 250, 500, and 1,000 nM), and dissociation of GSK-3β-TWS119 complexes is followed for 300 seconds. Evaluation of SPR data is performed by using the S51 evaluation software package. Data from two independent titration experiments performed on four different surfaces are averaged. A 1:1 binding model is assumed for the determination of thermodynamic and kinetic binding constants.

Animal Study: [4]

Animal Models Pmel-1 TCR-transgenic mice and pmel-1 ly5.1 double-transgenic mice and pmel-1 Thy1.1 double-transgenic mice
Formulation TWS119 is dissolved in DMSO.
Dosages 30 mg/kg
Administration Intraperitoneal injection

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)
Body Surface Area (m2)0.0070.0250.
Km factor36128520
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)


[1] Ding S, et al, Pro Natl Acad Sci U S A, 2003, 100(13), 7632-7637.

[2] Ding S, et al, Nat Biotechnol, 2004, 22(7), 833-840.

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Chemical Information

Download TWS119 SDF
Molecular Weight (MW) 318.33


CAS No. 601514-19-6
Storage 3 years -20℃powder
2 years -80℃in solvent
Synonyms N/A
Solubility (25°C) * 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
* <1 mg/ml means slightly soluble or insoluble.
* 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 Name 3-(6-(3-aminophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yloxy)phenol

Tech Support

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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