tcsc0224 TWS119

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

IC50 & Target: IC50: 30 nM (GSK-3β)^[1]

In Vitro: TWS119 induces neuronal differentiation in P19 EC cells and primary mouse ESCs. TWS119 binds to GSK-3β with K_D 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].