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

Autor:	Lefranc J; Pharmaceuticals, Research and Development , Bayer AG , 13353 Berlin , Germany., Schulze VK; Pharmaceuticals, Research and Development , Bayer AG , 13353 Berlin , Germany., Hillig RC; Pharmaceuticals, Research and Development , Bayer AG , 13353 Berlin , Germany., Briem H; Pharmaceuticals, Research and Development , Bayer AG , 13353 Berlin , Germany., Prinz F; Pharmaceuticals, Research and Development , Bayer AG , 13353 Berlin , Germany., Mengel A; Pharmaceuticals, Research and Development , Bayer AG , 13353 Berlin , Germany., Heinrich T; Pharmaceuticals, Research and Development , Bayer AG , 13353 Berlin , Germany., Balint J; ASCA GmbH (Angewandte Synthesechemie Adlershof) , 12489 Berlin , Germany., Rengachari S; Leicester Institute of Structural and Chemical Biology, Department of Molecular and Cell Biology , University of Leicester , Lancaster Road , LE1 7RH Leicester , U.K., Irlbacher H; Pharmaceuticals, Research and Development , Bayer AG , 13353 Berlin , Germany., Stöckigt D; Pharmaceuticals, Research and Development , Bayer AG , 13353 Berlin , Germany., Bömer U; Pharmaceuticals, Research and Development , Bayer AG , 13353 Berlin , Germany., Bader B; Pharmaceuticals, Research and Development , Bayer AG , 13353 Berlin , Germany., Gradl SN; Pharmaceuticals, Research and Development , Bayer AG , 13353 Berlin , Germany., Nising CF; Pharmaceuticals, Research and Development , Bayer AG , 13353 Berlin , Germany., von Nussbaum F; Pharmaceuticals, Research and Development , Bayer AG , 13353 Berlin , Germany., Mumberg D; Pharmaceuticals, Research and Development , Bayer AG , 13353 Berlin , Germany., Panne D; Leicester Institute of Structural and Chemical Biology, Department of Molecular and Cell Biology , University of Leicester , Lancaster Road , LE1 7RH Leicester , U.K.; European Molecular Biology Laboratory , 38042 Grenoble , France., Wengner AM; Pharmaceuticals, Research and Development , Bayer AG , 13353 Berlin , Germany.
Jazyk:	angličtina
Zdroj:	Journal of medicinal chemistry [J Med Chem] 2020 Jan 23; Vol. 63 (2), pp. 601-612. Date of Electronic Publication: 2020 Jan 10.
DOI:	10.1021/acs.jmedchem.9b01460
Abstrakt:	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.
Databáze:	MEDLINE
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