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 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.