1. PI3K/Akt/mTOR
    Stem Cell/Wnt
    Autophagy
  2. GSK-3
    Autophagy
  3. TWS119

TWS119 

Cat. No.: HY-10590 Purity: >98.0%
Handling Instructions

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

For research use only. We do not sell to patients.

TWS119 Chemical Structure

TWS119 Chemical Structure

CAS No. : 601514-19-6

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Based on 6 publication(s) in Google Scholar

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Description

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

IC50 & Target[1]

GSK-3β

30 nM (IC50)

In Vitro

TWS119 induces neuronal differentiation in P19 EC cells and primary mouse ESCs. TWS119 binds to GSK-3β with KD of 126 nM, and modulates the activity of the complex, triggering downstream transcriptional events that lead the neuronal induction[1]. TWS119 (< 4 μM) significantly enhances the proliferation and survival of γδT cells via activation of the mammalian target of rapamycin (mTOR) pathway, upregulation of the expression of anti-apoptotic protein Bcl-2 and inhibition of cleaved caspase-3. TWS119 (0-8 μM) induces the generation of CD62L+γδT or CCR5+γδT cell phenotypes. TWS119 (0.5, 1.0 and 2 μM) increases the expression level of granzyme B in a dose-dependent manner. TWS119 also enhances the cytolytic activity of γδT cells against tumour cells in vitro[3].

In Vivo

TWS119 (30 mg/kg, i.p.) improves the neurologic function and decreases neurologic deficit dcore in rtPA-treated MCAO rats. TWS119 effectively relieves cerebral edema, and reduces cerebral infarction in rats treated with rtPA. TWS119 also effectively decreases blood-brain barrier permeability in rtPA-Treated MCAO Rats and attenuates rtPA-induced hemorrhage in ischemic brain tissue. Futhermore, TWS119 activates the Wnt/β-Catenin signaling pathway and increases the expression of Claudin-3 and ZO-1[2].

Molecular Weight

318.33

Formula

C₁₈H₁₄N₄O₂

CAS No.

601514-19-6

SMILES

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

Shipping

Room temperature in continental US; may vary elsewhere.

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Solvent & Solubility
In Vitro: 

DMSO : ≥ 50 mg/mL (157.07 mM)

*"≥" means soluble, but saturation unknown.

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 3.1414 mL 15.7070 mL 31.4139 mL
5 mM 0.6283 mL 3.1414 mL 6.2828 mL
10 mM 0.3141 mL 1.5707 mL 3.1414 mL
*Please refer to the solubility information to select the appropriate solvent.
In Vivo:
  • 1.

    Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% saline

    Solubility: ≥ 2.5 mg/mL (7.85 mM); Clear solution

  • 2.

    Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in saline)

    Solubility: ≥ 2.5 mg/mL (7.85 mM); Clear solution

*All of the co-solvents are provided by MCE.
References
Cell Assay
[3]

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[3].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[2]

All rats are randomly divided into four groups as follows: Sham group-rats undego the same surgical procedure, but the filament is not inserted and they receive 1 mL of dimethyl sulfoxide (1 % DMSO in saline); Vehicle group-rats undergo MCAO and receive 1 mL of DMSO; rtPA group-rats underwent MCAO and receive rtPA (10 mg/kg, Actilyse®) at 4 h after MCAO; and rtPA+TWS119 group-rats undergo MCAO and receive intraperitoneal TWS119 (30 mg/kg, dissolved in 1 mL 1 % DMSO) immediately after rtPA injection at 4 h after MCAO[2].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
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Keywords:

TWS119TWS 119TWS-119GSK-3AutophagyGlycogen synthase kinase-3Glycogen synthase kinase 3Inhibitorinhibitorinhibit

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