Novel indolylmaleimide acts as GSK-3 beta inhibitor in human neural progenitor cells

作者：Schmoele Anne Caroline; Brennfuehrer Anne; Karapetyan Gnuni; Jaster Robert; Pews Davtyan Anahit; Huebner Rayk; Ortinau Stefanie; Beller Matthias; Rolfs Arndt; Frech Moritz J^*

来源：Bioorganic & Medicinal Chemistry, 2010, 18(18): 6785-6795.

DOI：10.1016/j.bmc.2010.07.045

• beta-Catenin
• GSK-3 inhibitors
• Indolylmaleimides
• Human neural progenitor cells
• ReNcell VM cell

The Wnt pathway is involved in cellular processes linked to either proliferation or differentiation. Therefore small molecules offer an attractive opportunity to modulate this pathway, whereas the key enzyme GSK-3 beta is of special interest. In this study, non-symmetrically substituted indolylmaleimides have been synthesized and their ability to function as GSK-3 beta inhibitors has been investigated in a human neural progenitor cell line. Among the newly synthesized compounds, the substance IM-12 showed a significant activity in several biological tests which was comparable or even outplayed the effects of the known GSK-3 beta inhibitor SB-216763. Furthermore the treatment of human neural progenitor cells with IM-12 resulted in an increase of neuronal cells. Therefore we conclude that indolylmaleimides act via the canonical Wnt signalling pathway by inhibition of the key enzyme GSK-3 beta.

• 出版日期2010-9-15