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  • Discovery and Characterization of the Potent and Highly Selective (Piperidin-4-yl)pyrido[3,2- d]pyrimidine Based in Vitro Probe BAY-885 for the Kinase ERK5.

Discovery and Characterization of the Potent and Highly Selective (Piperidin-4-yl)pyrido[3,2- d]pyrimidine Based in Vitro Probe BAY-885 for the Kinase ERK5.

Journal of medicinal chemistry (2018-12-20)
Duy Nguyen, Clara Lemos, Lars Wortmann, Knut Eis, Simon J Holton, Ulf Boemer, Dieter Moosmayer, Uwe Eberspaecher, Joerg Weiske, Christian Lechner, Stefan Prechtl, Detlev Suelzle, Franziska Siegel, Florian Prinz, Ralf Lesche, Barbara Nicke, Katrin Nowak-Reppel, Herbert Himmel, Dominik Mumberg, Franz von Nussbaum, Carl F Nising, Marcus Bauser, Andrea Haegebarth
PMID30563338
ABSTRACT

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 report the identification of a highly potent and selective ERK5 inhibitor BAY-885 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.