6HKM

Crystal structure of Compound 1 with ERK5

Summary for 6HKM

• Entry DOI: 10.2210/pdb6hkm/pdb
• Descriptor: Mitogen-activated protein kinase 7, [4-(6,7-dimethoxyquinazolin-4-yl)piperidin-1-yl]-[4-(trifluoromethyloxy)phenyl]methanone (3 entities in total)
• Functional Keywords: erk5 kinase, immune system, transferase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 40187.18

Authors

Nguyen, D.,Lemos, C.,Wortmann, L.,Eis, K.,Holton, S.J.,Boemer, U.,Lechner, C.,Prechtl, S.,Suelze, D.,Siegel, F.,Prinz, F.,Lesche, R.,Nicke, B.,Mumberg, D.,Bauser, M.,Haegebarth, A. (deposition date: 2018-09-07, release date: 2019-02-27, Last modification date: 2024-05-15)

Primary citation

Nguyen, D.,Lemos, C.,Wortmann, L.,Eis, K.,Holton, S.J.,Boemer, U.,Moosmayer, D.,Eberspaecher, U.,Weiske, J.,Lechner, C.,Prechtl, S.,Suelzle, D.,Siegel, F.,Prinz, F.,Lesche, R.,Nicke, B.,Nowak-Reppel, K.,Himmel, H.,Mumberg, D.,von Nussbaum, F.,Nising, C.F.,Bauser, M.,Haegebarth, A.
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., 62:928-940, 2019

PubMed 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.

PubMed: 30563338
DOI: 10.1021/acs.jmedchem.8b01606

Experimental method

X-RAY DIFFRACTION (2.47 Å)