Structure-based design of benzo[e]isoindole-1,3-dione derivatives as selective GSK-3β inhibitors to activate Wnt/β-catenin pathway

被引：23

作者：

Yue, Hong ^{[1
]}

Lu, Feng ^{[1
]}

Shen, Chen ^{[1
]}

Quan, Jun-Min ^{[1
]}

机构：

[1] Peking Univ, Key Lab Struct Biol, Sch Chem Biol & Biotechnol, Shenzhen Grad Sch, Shenzhen 518055, Peoples R China

来源：

BIOORGANIC CHEMISTRY | 2015年 / 61卷

关键词：

GSK-3; beta; Inhibitor; Wnt/beta-catenin pathway; Neurodegenerative diseases; CDK2; GLYCOGEN-SYNTHASE KINASE-3; CDK/GSK-3; INHIBITORS; CRYSTAL-STRUCTURE; WNT; BINDING; PHOSPHORYLATION; CDK2; NEURODEGENERATION; DISEASE; BRAIN;

D O I：

10.1016/j.bioorg.2015.05.009

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：

Deregulation of Wnt/beta-catenin pathway is closely related to the pathogenesis of neurodegenerative diseases such as Alzheimer's disease (AD), and glycogen synthase kinase 3 beta (GSK-3 beta), the central negative regulator of Wnt pathway, is regarded as an important target for these diseases. Here, we report a series of benzo[e]isoindole-1,3-dione derivatives as selective GSK-3 beta inhibitors by rational-design and synthesis, which show high selectivity against GSK-3 beta over Cyclin-dependent kinase 2 (CDK2), and significantly activate the cellular Wnt/beta-catenin pathway. The structure-activity relationship of these GSK-3 beta inhibitors was also explored by in silico molecular docking. (C) 2015 Elsevier Inc. All rights reserved.

引用

页码：21 / 27

页数：7