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.

中文翻译：

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发现了BAY-985，一种高度选择性的TBK1 /IKKε抑制剂。

丝氨酸/苏氨酸激酶TBK1（TANK结合激酶1）及其同源物IKKε是核因子κB（IκB）激酶家族抑制剂的非典型成员。这些激酶在多种细胞途径中，特别是在炎症中起重要作用。在这里，我们描述了我们对苯并咪唑家族的研究，以及强效和高选择性TBK1 /IKKε抑制剂BAY-985的鉴定。BAY-985抑制干扰素调节因子3的细胞磷酸化，并在黑色素瘤细胞系SK-MEL-2中显示抗增殖功效，但在SK-MEL-2人黑色素瘤异种移植模型中仅显示出较弱的抗肿瘤活性。