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

被引：44

作者：

Schmoele, Anne-Caroline ^{[1
]}

Brennfuehrer, Anne ^{[2
]}

Karapetyan, Gnuni ^{[2
]}

Jaster, Robert ^{[3
]}

Pews-Davtyan, Anahit ^{[2
]}

Huebner, Rayk ^{[1
]}

Ortinau, Stefanie ^{[1
]}

Beller, Matthias ^{[2
]}

Rolfs, Arndt ^{[1
]}

Frech, Moritz J. ^{[1
]}

机构：

[1] Univ Rostock, Ctr Mental Hlth, Albrecht Kossel Inst Neuroregenerat AKos, D-18147 Rostock, Germany

[2] Univ Rostock, Leibniz Inst Katalyse eV, D-18059 Rostock, Germany

[3] Univ Rostock, Dept Internal Med 2, Div Gastroenterol, D-18057 Rostock, Germany

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2010年 / 18卷 / 18期

关键词：

beta-Catenin; GSK-3; inhibitors; Indolylmaleimides; Human neural progenitor cells; ReNcell VM cell; GLYCOGEN-SYNTHASE KINASE-3; SMALL-MOLECULE INHIBITORS; FLUORINE; PROLIFERATION; DIFFERENTIATION; EXPRESSION; REGULATOR; PATHWAYS; NEURONS; ANALOGS;

D O I：

10.1016/j.bmc.2010.07.045

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：6785 / 6795

页数：11

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