Discovery of novel class 1 phosphatidylinositide 3-kinases (PI3K) fragment inhibitors through structure-based virtual screening

被引：23
|
作者：
Giordanetto, Fabrizio [1 ]
Kull, Bengt [2 ]
Dellsen, Anita [2 ]
机构：
[1] AstraZeneca R&D, Lead Generat, SE-43183 Molndal, Sweden
[2] AstraZeneca R&D, Biosci, SE-43183 Molndal, Sweden
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 02期
关键词：
Docking; Fragment-based; Phosphatidylinositide; 3-kinase; PI3K; p110 beta inhibitor; Virtual screening; PIK3CA GENE; PHOSPHOINOSITIDE; 3-KINASES; LIGAND SPECIFICITY; DRUG DISCOVERY; OVARIAN; KINASE; MECHANISMS; MUTATIONS; CANCERS; DOCKING;
D O I：
10.1016/j.bmcl.2010.11.087
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
The discovery of ligand efficient and lipophilicity efficient fragment inhibitors of class 1 phosphatidylinositide 3-kinases (PI3K) is reported. A fragment version of the AstraZeneca compound bank was docked to a homology model of the PI3K p110 beta isoform. Interaction-based scoring of the predicted binding poses served to further prioritise the virtual fragment hits. Experimental screening confirmed potency for a total of 18 fragment inhibitors, belonging to five different structural classes. (C) 2010 Elsevier Ltd. All rights reserved.
引用
收藏
页码：829 / 835
页数：7
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