TWS119

TWS119 is a cell-permeable pyrrolopyrimidine compound that acts as a glycogen synthase kinase-3 beta (GSK-3 beta) inhibitor. TWS119 is thought to bind GSK-3 beta with high-affinity and increases the level of beta-catenin, a downstream substrate of GSK-3 beta in the Wnt signaling pathway. TWS119 induces neuronal differentiation in pluripotent murine embryonal carcinoma cells and embryonic stem cells (ESC). Because neuronal differentiation can be achieved without embryoid bodies (EB) formation and RA treatment, TWS119 may act by a novel mechanism on early processes involved in determining cell fate. TWS119 treatment towards hepatic stellate cells leads to reduced β-catenin phosphorylation, induces nuclear translocation of β-catenin, elevates glutamine synthetase production, impedes synthesis of smooth muscle actin and Wnt-5a, but promotes the expression of glial fibrillary acidic protein, Wnt-10b, and paired-like homeodomain transcription factor 2c.