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Revised TBK1 Manuscript 3.pdf (1.38 MB)

Discovery of BAY-985, a Highly Selective TBK1/IKK epsilon Inhibitor

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journal contribution
posted on 2020-04-02, 14:46 authored by Julien Lefranc, Volker Klaus Schulze, Roman Christian Hillig, Hans Briem, Florian Prinz, Anne Mengel, Tobias Heinrich, Jozsef Balint, Srinivasan Rengachari, Horst Irlbacher, Detlef Stoeckigt, Ulf Boemer, Benjamin Bader, Stefan Nikolaus Gradl, Carl Friedrich Nising, Franz von Nussbaum, Dominik Mumberg, Daniel Panne, Antje Margret Wengner
The serine/threonine kinase TBK1 (TANK-binding kinase 1) and its homologue IKKϵ are noncanonical members of the inhibitor of the nuclear factor κB (IκB) kinase family. These kinases play important roles in multiple cellular pathways and, in particular, in inflammation. Herein, we describe our investigations on a family of benzimidazoles and the identification of the potent and highly selective TBK1/IKKϵ inhibitor BAY-985. BAY-985 inhibits the cellular phosphorylation of interferon regulatory factor 3 and displays antiproliferative efficacy in the melanoma cell line SK-MEL-2 but showed only weak antitumor activity in the SK-MEL-2 human melanoma xenograft model.

History

Citation

J. Med. Chem. 2020, 63, 2, 601-612

Author affiliation

Leicester Institute of Structural and Chemical Biology, Department of Molecular and Cell Biology

Version

  • AM (Accepted Manuscript)

Published in

Journal of Medicinal Chemistry

Volume

63

Issue

2

Pagination

601 - 612

Publisher

American Chemical Society

issn

0022-2623

eissn

1520-4804

Copyright date

2020

Available date

2020-12-20

Publisher version

https://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.9b01460

Spatial coverage

United States

Language

English