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

页码：2021 / 2024

页数：4

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