1. Academic Validation
  2. 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

  • J Med Chem. 2019 Jan 24;62(2):928-940. doi: 10.1021/acs.jmedchem.8b01606.
Duy Nguyen 1 Clara Lemos 1 Lars Wortmann 1 Knut Eis 1 Simon J Holton 1 Ulf Boemer 1 Dieter Moosmayer 1 Uwe Eberspaecher 1 Joerg Weiske 1 Christian Lechner 1 Stefan Prechtl 1 Detlev Suelzle 1 Franziska Siegel 1 Florian Prinz 1 Ralf Lesche 1 Barbara Nicke 1 Katrin Nowak-Reppel 1 Herbert Himmel 1 Dominik Mumberg 1 Franz von Nussbaum 1 Carl F Nising 1 Marcus Bauser 1 Andrea Haegebarth 1
Affiliations

Affiliation

  • 1 Research & Development, Pharmaceuticals , Bayer AG , 13353 Berlin , Germany.
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.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-112082
    99.27%, ERK5 Inhibitor
    ERK