IM-12 is a potent inhibitor of GSK-3β with IC50 value of 53 nM [1].
Glycogen synthase kinase-3β (GSK-3β) is a proline-directed serine-threonine kinase and is involved in neuronal cell development, energy metabolism and body pattern formation. Inhibition of GSK-3β can cause β-catenin accumulation.
IM-12 is a potent GSK-3β inhibitor. In ReNcell VM cells, IM-12 significantly increased total β-catenin by 27% and at a concentration of 3 µM increased the β-catenin amount most. In ReNcell VM cells, IM-12 (3 µM) inhibited GSK-3β to a remaining activity of 27 ± 5%. Also, IM-12 significantly increased the cell doubling time to 26.5 ± 0.9 h and significantly inhibited cell proliferation. In ST14A cells, IM-12 caused an accumulation of β-catenin around the nucleus. In ReNcell VM cells transfected with TOPFlash, IM-12 increased TCF-activity. In cells transfected with TOP and pCAGGS-S33Y (a vector containing β-catenin), IM-12 significantly increased TCF-activity by 270%. In ReNcell VM cells, IM-12 significantly increased the level of βIIItub+ cells to 3.7 ± 0.7%, which suggested that IM-12 increased neuronal differentiation [1].
Reference:
[1]. Schmöle AC, Brennführer A, Karapetyan G, et al. Novel indolylmaleimide acts as GSK-3beta inhibitor in human neural progenitor cells. Bioorg Med Chem, 2010, 18(18): 6785-6795.