title: Novel indolylmaleimide acts as GSK-3beta inhibitor in human neural progenitor cells.
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-3beta is of special interest. In this study, non-symmetrically substituted indolylmaleimides have been synthesized and their ability to function as GSK-3beta 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-3beta 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-3beta.
authors: Albrecht-Kossel-Institute for Neuroregeneration (AKos), Center for Mental Health, University of Rostock, Gehlsheimer Str. 20, D-18147 Rostock, Germany.
authors: Anne-Caroline
authors: AC
authors: Schmöle
authors: Anne
authors: A
authors: Brennführer
authors: Gnuni
authors: G
authors: Karapetyan
authors: Robert
authors: R
authors: Jaster
authors: Anahit
authors: A
authors: Pews-Davtyan
authors: Rayk
authors: R
authors: Hübner
authors: Stefanie
authors: S
authors: Ortinau
authors: Matthias
authors: M
authors: Beller
authors: Arndt
authors: A
authors: Rolfs
authors: Moritz J
authors: MJ
authors: Frech
mesh_terms: D002454:Cell Differentiation; D049109:Cell Proliferation; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008301:Maleimides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D009474:Neurons / Q000166:cytology*; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000201:enzymology*; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: C554531:3-(4-fluorophenylethylamino)-1-methyl-4-(2-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione; D007211:Indoles; D008301:Maleimides; D047428:Protein Kinase Inhibitors; C417521:SB 216763; D051153:Wnt Proteins; D051176:beta Catenin; C043592:maleimide; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3