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 PMID: 30563338

ADC Targets in Oncology

2026-04-10

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

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.