Discovery of BAY-985, a Highly Selective TBK1/IKK epsilon Inhibitor
journal contributionposted 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.
CitationJ. Med. Chem. 2020, 63, 2, 601-612
Author affiliationLeicester Institute of Structural and Chemical Biology, Department of Molecular and Cell Biology
- AM (Accepted Manuscript)