Document Detail


Novel indolylmaleimide acts as GSK-3beta inhibitor in human neural progenitor cells.
MedLine Citation:
PMID:  20708937     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Anne-Caroline Schmöle; Anne Brennführer; Gnuni Karapetyan; Robert Jaster; Anahit Pews-Davtyan; Rayk Hübner; Stefanie Ortinau; Matthias Beller; Arndt Rolfs; Moritz J Frech
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-07-25
Journal Detail:
Title:  Bioorganic & medicinal chemistry     Volume:  18     ISSN:  1464-3391     ISO Abbreviation:  Bioorg. Med. Chem.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-09-06     Completed Date:  2010-12-30     Revised Date:  2011-11-02    
Medline Journal Info:
Nlm Unique ID:  9413298     Medline TA:  Bioorg Med Chem     Country:  England    
Other Details:
Languages:  eng     Pagination:  6785-95     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2010 Elsevier Ltd. All rights reserved.
Affiliation:
Albrecht-Kossel-Institute for Neuroregeneration (AKos), Center for Mental Health, University of Rostock, Gehlsheimer Str. 20, D-18147 Rostock, Germany.
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MeSH Terms
Descriptor/Qualifier:
Cell Differentiation
Cell Proliferation
Glycogen Synthase Kinase 3 / antagonists & inhibitors*,  metabolism
Humans
Indoles / chemical synthesis,  chemistry*,  pharmacology
Maleimides / chemical synthesis,  chemistry*,  pharmacology
Neurons / cytology*
Protein Kinase Inhibitors / chemical synthesis,  chemistry*,  pharmacology
Signal Transduction
Stem Cells / cytology,  enzymology*
Wnt Proteins / metabolism
beta Catenin / metabolism
Chemical
Reg. No./Substance:
0/3-(4-fluorophenylethylamino)-1-methyl-4-(2-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione; 0/Indoles; 0/Maleimides; 0/Protein Kinase Inhibitors; 0/SB 216763; 0/Wnt Proteins; 0/beta Catenin; 541-59-3/maleimide; EC 2.7.11.1/glycogen synthase kinase 3 beta; EC 2.7.11.26/Glycogen Synthase Kinase 3

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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