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

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 invest...

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Published in:Journal of medicinal chemistry 2020-01, Vol.63 (2), p.601-612
Main Authors: Lefranc, Julien, Schulze, Volker Klaus, Hillig, Roman Christian, Briem, Hans, Prinz, Florian, Mengel, Anne, Heinrich, Tobias, Balint, Jozsef, Rengachari, Srinivasan, Irlbacher, Horst, Stöckigt, Detlef, Bömer, Ulf, Bader, Benjamin, Gradl, Stefan Nikolaus, Nising, Carl Friedrich, von Nussbaum, Franz, Mumberg, Dominik, Panne, Daniel, Wengner, Antje Margret
Format: Article
Language:English
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Summary: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.
ISSN:0022-2623
1520-4804
DOI:10.1021/acs.jmedchem.9b01460