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

Anne Caroline Schmöle, Anne Brennführer, Gnuni Karapetyan, Robert Jaster, Anahit Pews-Davtyan, Rayk Hübner, Stefanie Ortinau, Matthias Beller, Arndt Rolfs, Moritz J. Frech

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

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-3β is of special interest. In this study, non-symmetrically substituted indolylmaleimides have been synthesized and their ability to function as GSK-3β 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-3β 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-3β.

Original languageEnglish
Pages (from-to)6785-6795
Number of pages11
JournalBioorganic and Medicinal Chemistry
Volume18
Issue number18
DOIs
StatePublished - 15 Sep 2010
Externally publishedYes

Keywords

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

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