Structure-based virtual screening approach to the discovery of phosphoinositide 3-kinase alpha inhibitors

被引：6
|
作者：
Park, Hwangseo [1 ]
Choi, Hwanho [1 ]
Hong, Seunghee [2 ]
Kim, Donghee [2 ]
Oh, Dal-Seok [3 ]
Hong, Sungwoo [2 ]
机构：
[1] Sejong Univ, Dept Biosci & Biotechnol, Seoul 143747, South Korea
[2] Korea Adv Inst Sci & Technol, Dept Chem, Taejon 305701, South Korea
[3] Korea Inst Oriental Med, Brain Dis Res Ctr, Taejon 305811, South Korea
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 07期
关键词：
Virtual screening; Docking; PI3K alpha; Inhibitor; Anticancer agents; BIOLOGICAL EVALUATION; PI3; KINASE; SOLVATION; MUTATIONS; CANCER; GDC-0941; POTENT;
D O I：
10.1016/j.bmcl.2011.02.015
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Phosphoinositide 3-kinase alpha (PI3K alpha) has proved to be an attractive target for the development of therapeutics for the treatment of cancer. Herein we report a successful application of the structure-based virtual screening to identify the novel inhibitors of PI3K alpha. These inhibitors have desirable physicochemical properties as a drug candidate and reveal a moderate potency with IC50 values ranging from 20 to 40 mu M. Therefore, they deserve a consideration for further development by structure-activity relationship (SAR) studies to optimize the inhibitory activities. Structural features relevant to the stabilization of the newly identified inhibitors in the ATP-binding site of PI3K alpha are addressed in detail. (C) 2011 Elsevier Ltd. All rights reserved.
引用
收藏
页码：2021 / 2024
页数：4
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