Discovery of NVP-BYL719 a potent and selective phosphatidylinositol-3 kinase alpha inhibitor selected for clinical evaluation

被引：377

作者：

Furet, Pascal ^{[1
]}

Guagnano, Vito ^{[1
]}

Fairhurst, Robin A. ^{[1
]}

Imbach-Weese, Patricia ^{[1
]}

Bruce, Ian ^{[1
]}

Knapp, Mark ^{[1
]}

Fritsch, Christine ^{[1
]}

Blasco, Francesca ^{[1
]}

Blanz, Joachim ^{[1
]}

Aichholz, Reiner ^{[1
]}

Hamon, Jacques ^{[1
]}

Fabbro, Doriano ^{[1
]}

Caravatti, Giorgio ^{[1
]}

机构：

[1] Novartis Inst BioMed Res, CH-4002 Basel, Switzerland

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2013年 / 23卷 / 13期

关键词：

PI3K inhibitors; Antitumor agent; I PI3 KINASE; PIK3CA GENE; BREAST CANCERS; GAMMA-PYRONES; MUTATIONS; PATHWAY; OVARIAN; IDENTIFICATION; CARCINOMAS; NVP-BKM120;

D O I：

10.1016/j.bmcl.2013.05.007

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Phosphatidylinositol-3-kinase alpha (PI3K alpha) is a therapeutic target of high interest in anticancer drug research. On the basis of a binding model rationalizing the high selectivity and potency of a particular series of 2-aminothiazole compounds in inhibiting PI3K alpha, a medicinal chemistry program has led to the discovery of the clinical candidate NVP-BYL719. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：3741 / 3748

页数：8

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