Discovery of novel morpholino-quinoxalines as PI3Kα inhibitors by pharmacophore-based screening

被引：19

作者：

Wu, Peng ^{[1
]}

Su, Yi ^{[2
]}

Liu, Xiaowen ^{[2
]}

Yan, Jingying ^{[1
]}

Ye, Yong ^{[1
]}

Zhang, Lei ^{[2
]}

Xu, Jianchao ^{[1
]}

Weng, Shaoyu ^{[1
]}

Li, Yani ^{[1
]}

Liu, Tao ^{[1
]}

Dong, Xiaowu ^{[1
]}

Sun, Maotang ^{[1
]}

Yang, Bo ^{[2
]}

He, Qiaojun ^{[2
]}

Hu, Yongzhou ^{[1
]}

机构：

[1] Zhejiang Univ, Coll Pharmaceut Sci, ZJU ENS Joint Lab Med Chem, Hangzhou 310058, Zhejiang, Peoples R China

[2] Zhejiang Univ, Coll Pharmaceut Sci, Inst Pharmacol & Toxicol, Hangzhou 310058, Zhejiang, Peoples R China

来源：

MEDCHEMCOMM | 2012年 / 3卷 / 06期

关键词：

BIOLOGICAL EVALUATION; CANCER; PI3K; MUTATIONS; 3-KINASE; THERAPY; PATHWAY; KINASE; TARGET;

D O I：

10.1039/c2md00255h

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：

A pharmacophore model of PI3K alpha inhibitors was built using the DiscoveryStudio 2.0 package. Pharmacophore-based screening (PBS) retrieved a series of novel morpholino-quinoxalines as PI3K alpha inhibitors, as exemplified by 1a (PI3K alpha IC50: 0.44 mu M). All target compounds showed good in vitro cytotoxicity against tested human cell lines. A pharmacophore mapping analysis and docking study indicated that both the morpholino group and the sulfonyl group contributed significantly to the potent PI3K alpha inhibitory activity and cytotoxicity of the compounds.

引用

页码：659 / 662

页数：4

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