Preliminary exploring of the relationship between the inhibition of TBK1 by amelexanox and its clinical side impact
Objective Taking the anti-inflammatory drug amlexanox as an example,the effect of the structural analog of this kind of marine halomonas metabolites inhibiting TBK1 activity on natural immunity and the potential relationship with clinical side effects were studied.Methods The effects of amlexanox on pathogenic infections and associated inflammatory pathways were evaluated in cell and animal models utilizing molecular biology and virology.Results Amlexanox and its analogues marine Halomonas sp.metabolites were potent inhibitors of TBK1.Amlexanox did not significantly inhibit the immune responses to pathogen stimuli.Tricyclic amine structural compounds represented by amlexanox inhibited TBK1(TANK-binding kinase 1)activity and probably did not directly increase infection probability.