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Published on: January 22, 2019
Identification of pharmacological inhibitors of the MEK5/ERK5 pathway
Revati J Tatake1, Margaret M O'Neill, Charles A Kennedy
1Department of Cardiovascular Disease, Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, CT 06877, USA.
Abstract:
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.
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