Flipped out: Structure-guided design of selective pyrazolylpyrrole ERK inhibitors

被引：112

作者：

Aronov, Alex M. ^{[1
]}

Baker, Christopher ^{[1
]}

Bemis, Guy W. ^{[1
]}

Cao, Jingrong ^{[1
]}

Chen, Guanjing ^{[1
]}

Ford, Pamella J. ^{[1
]}

Germann, Ursula A. ^{[1
]}

Green, Jeremy ^{[1
]}

Hale, Michael R. ^{[1
]}

Jacobs, Marc ^{[1
]}

Janetka, James W. ^{[1
]}

Maltais, Francois ^{[1
]}

Martinez-Botella, Gabriel ^{[1
]}

Namchuk, Mark N. ^{[1
]}

Straub, Judy ^{[1
]}

Tang, Qing ^{[1
]}

Xie, Xiaoling ^{[1
]}

机构：

[1] Vertex Pharmaceut Inc, Cambridge, MA 02139 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2007年 / 50卷 / 06期

关键词：

D O I：

10.1021/jm061381f

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The Ras/Raf/MEK/ERK signal transduction is a key oncogenic pathway implicated in a variety of human cancers. We have identified a novel series of pyrazolylpyrroles as inhibitors of ERK. Aided by the discovery of two distinct binding modes for the pyrazolylpyrrole scaffold, structure-guided optimization culminated in the discovery of 6p, a potent and selective inhibitor of ERK.

引用

页码：1280 / 1287

页数：8

共 26 条

[1] A novel mode of Gleevec binding is revealed by the structure of spleen tyrosine kinase [J].