Identification of pharmacological inhibitors of the MEK5/ERK5 pathway

被引：132
|
作者：
Tatake, Revati J. [1 ]
O'Neill, Margaret M. [1 ]
Kennedy, Charles A. [1 ]
Wayne, Anita L. [1 ]
Jakes, Scott [1 ]
Wu, Di [2 ]
Kugler, Stanley Z., Jr. [2 ]
Kashem, Mohammed A. [2 ]
Kaplita, Paul [3 ]
Snow, Roger J. [2 ]
机构：
[1] Boehringer Ingelheim Pharmaceut Inc, Dept Cardiovasc Dis, Ridgefield, CT 06877 USA
[2] Boehringer Ingelheim Pharmaceut Inc, Dept Med Chem, Ridgefield, CT 06877 USA
[3] Boehringer Ingelheim Pharmaceut Inc, Dept Drug Discovery Support, Ridgefield, CT 06877 USA
来源：
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2008年 / 377卷 / 01期
关键词：
MEK5; ERK5; Kinase inhibitors; Pharmacological inhibitors;
D O I：
10.1016/j.bbrc.2008.09.087
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：
We have identified two novel MEK5 inhibitors, BIX02188 and BIX02189, which inhibited catalytic function of purified, MEK5 enzyme. The MEK5 inhibitors blocked phosphorylation of ERK5, without affecting phosphorylation of ERK1/2 in sorbitol-stimulated HeLa cells. The compounds also inhibited transcriptional activation of MEF2C, a downstream substrate of the MEK5/ERK5 signaling cascade, in a cellular trans-reporter assay system. These inhibitors offer novel pharmacological tools to better characterize the role of the MEK5/ERK5 pathway in various biological systems. (C) 2008 Elsevier Inc. All rights reserved.
引用
收藏
页码：120 / 125
页数：6
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