2. Academic Validation
  3. Discovery of BAY-985, a Highly Selective TBK1/IKKε Inhibitor

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

  • J Med Chem. 2020 Jan 23;63(2):601-612. doi: 10.1021/acs.jmedchem.9b01460.
Julien Lefranc 1,  Volker Klaus Schulze 1,  Roman Christian Hillig 1,  Hans Briem 1,  Florian Prinz 1,  Anne Mengel 1,  Tobias Heinrich 1,  Jozsef Balint 2,  Srinivasan Rengachari 3,  Horst Irlbacher 1,  Detlef Stöckigt 1,  Ulf Bömer 1,  Benjamin Bader 1,  Stefan Nikolaus Gradl 1,  Carl Friedrich Nising 1,  Franz von Nussbaum 1,  Dominik Mumberg 1,  Daniel Panne 3 4,  Antje Margret Wengner 1
Affiliations

Affiliations

  • 1 Pharmaceuticals, Research and Development , Bayer AG , 13353 Berlin , Germany.
  • 2 ASCA GmbH (Angewandte Synthesechemie Adlershof) , 12489 Berlin , Germany.
  • 3 Leicester Institute of Structural and Chemical Biology, Department of Molecular and Cell Biology , University of Leicester , Lancaster Road , LE1 7RH Leicester , U.K.
  • 4 European Molecular Biology Laboratory , 38042 Grenoble , France.
PMID: 31859507 DOI: 10.1021/acs.jmedchem.9b01460
Abstract

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.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-133117
    99.88%, TBK1/IKKε Inhibitor
    IKK