Objective

Tank-binding kinase 1 (TBK1) and IkappaB kinase epsilon (IKKε) are related kinases. Toll-like receptors (TLR) on the surface of cells are involved in the innate immune response. They detect infection via recognition of conserved bacterial or viral constituents (1) which activate TBK1 and IKKε (2). This phosphorylates transcription factors of the IRF family and the release of pro-inflammatory cytokines like IP10 (3,4). In Chronic obstructive pulmonary disease (COPD) patients there is heightened expression of IP10 and its receptor CXCR3 in the submucosa and epithelium, resulting in an increase in recruitment of T cells. This is linked to disease severity (5). Inhibition of the TLR signalling pathway by modulation of TBK1 and IKKε activity gives an opportunity for treatment of inflammatory diseases (6).  A biochemistry assay was set up for TBK1 and IKKε, these assays were performed at K_m and 30 x K_m ATP for identification of ATP competition. The compounds were then profiled in a THP1 cell line, for inhibition of IP10 secretion after lipopolysaccharide (LPS) stimulation.  This work paves the way for the discovery of a new drug for COPD.