初探氨来呫诺抑制TBK1活性与其临床副作用的关系  

Preliminary Exploring of the Relationship Between the Inhibition of TBK1 by Amelexanox and Its Clinical Side Impact

作　　者：翟晓晨 张梅芳 武娟 杜凯欣 王鑫 ZHAI Xiaochen;ZHANG Meifang;WU Juan;DU Kaixin;WANG Xin(Key Laboratory of Marine Drugs,Ministry of Education,School of Medicine and Pharmacy,Ocean University of China,Qingdao 266003,China;Innovation Center for Marine Drug Screening and Evaluation,Marine Biomedical Research Institute of Qingdao,Qingdao 266100,China)

机构地区：[1]中国海洋大学海洋药物教育部重点实验室,医药学院,山东青岛266003 [2]青岛海洋生物医药研究院海洋创新药物药筛选与评价中心,山东青岛266100

出　　处：《中国海洋药物》2024年第4期73-79,共7页Chinese Journal of Marine Drugs

基　　金：国家自然科学基金项目(U22A20582)资助。

摘　　要：目的 以消炎药氨来呫诺为例,对该类海洋盐单胞菌代谢产物的结构类似物抑制TBK1活性对天然免疫的影响及与临床副作用的潜在关联进行研究。方法 运用分子生物学和病毒学手段,在细胞和动物模型中,评估氨来呫诺对病原体感染及相关炎症通路的影响。结果 氨来呫诺及其类似物是潜在的TBK1抑制剂;氨来呫诺不显著抑制机体对病原体刺激的应答;以氨来呫诺为代表的三环胺类结构化合物抑制TBK1 (TANK-binding kinase 1)活性可能不直接导致感染概率上升。Objective Amlexanox,an anti-inflammatory drug,is the analogue of a class of Halomonas sp.metabolites.Amlexanox increases the incidence of upper respiratory tract infection in the clinic,possibly related to immunosuppression.We studied amlexanox as an example to explore the effects of this kind of compound on innate immunity by inhibiting TBK1 activity and its potential association with clinical side effects.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.

关 键 词：氨来呫诺 海洋化合物 海洋Halomonas sp. TBK1 安全药理学研究 

分 类 号：R931.77[医药卫生—生药学]