Indexed on: 20 Dec '18Published on: 20 Dec '18Published in: Journal of Medicinal Chemistry
The availability of a chemical probe to study the role of a specific domain of a protein in a concentration- and time-dependent manner is of high value. Herein we reported the identification of a highly potent and selective ERK5 inhibitor BAY-855 by high-throughput screening and subsequent structure-based optimization. ERK5 is a key integrator of cellular signal transduction and it has been shown to play a role in various cellular processes such as proliferation, differentiation, apoptosis and cell survival. We could demonstrate that inhibition of ERK5 kinase and transcriptional activity with a small molecule did not translate into antiproliferative activity in different relevant cell models, which is in contrast to the results obtained by RNAi technology.