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TWS119

MCE China：TWS119

Brand：MedChemExpress (MCE)

Cat. No.HY-10590

CAS：601514-19-6

Purity：99.20%

Storage：Powder -20°C 3 years 4°C 2 years In solvent -80°C 1 year -20°C 6 months

Shipping：Room temperature in continental US; may vary elsewhere.

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

In Vitro：TWS119 induces neuronal differentiation in P19 EC cells and primary mouse ESCs. TWS119 (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[2].

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[1].

Animal Administration：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].

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[3].

IC50 & Target：GSK-3β 30 nM (IC50)

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References：

[1]. Wang W, et al. GSK-3β inhibitor TWS119 attenuates rtPA-induced hemorrhagic transformation and activates the Wnt/β-catenin signaling pathway after acute ischemic stroke in rats. Mol Neurobiol. 2016 Dec;53(10):7028-7036. Epub 2015 Dec 15.  [Content Brief]

[2]. Chen YQ, et al. Wnt pathway activator TWS119 enhances the proliferation and cytolytic activity of human γδT cells against colon cancer. Exp Cell Res. 2017 Nov 16. pii: S0014-4827(17)30587-6.  [Content Brief]