阿昔洛韦：一种治疗特应性、代谢和炎症性疾病的新型治疗药物。
Amlexanox: A Novel Therapeutic for Atopic, Metabolic, and Inflammatory Disease.
机构信息
Department of Pediatrics, RCHSD, San Diego, CA.
Brown University, Providence, RI.
出版信息
Yale J Biol Med. 2020 Dec 29;93(5):759-763. eCollection 2020 Dec.
Abstract
Amlexanox, a small molecule targeted therapy which has been used in the treatment of atopic conditions was previously but is not currently available in the United States. Amlexanox has also been legally utilized and administered in Japan as a treatment for asthma, a chronic pulmonary disease characterized by inflammation of the lower respiratory tract. Amlexanox's immune modulatory effects have been the subject of studies which have repurposed the drug for potential therapeutic applications in metabolic and inflammatory disease. Because amlexanox inhibits TANK-binding kinase1 (TBK1) and nuclear factor kB kinase epsilon (IKKε), several studies have demonstrated its usefulness through its evidence downregulation of the immune system and attenuation of downstream TBK1 signaling. Novel therapies, such as amlexanox, for inflammatory conditions such as asthma will continue to be of value in clinical management. This report summarizes key applications of the drug based on animal and human studies and explores its potential in treatment of metabolic and inflammatory diseases.
摘要
氨来呫诺，一种小分子靶向治疗药物，曾用于治疗特应性疾病，但目前在美国已不再使用。氨来呫诺在日本也被合法用于治疗哮喘，这是一种以呼吸道下部炎症为特征的慢性肺部疾病。氨来呫诺的免疫调节作用一直是研究的主题，该药物已被重新用于代谢和炎症性疾病的潜在治疗应用。由于氨来呫诺抑制 TANK 结合激酶 1（TBK1）和核因子 kB 激酶 ε（IKKε），因此几项研究通过其对免疫系统的证据下调和下游 TBK1 信号的衰减证明了其有用性。对于哮喘等炎症性疾病，氨来呫诺等新型疗法将继续在临床管理中具有价值。本报告根据动物和人体研究总结了该药物的关键应用，并探讨了其在治疗代谢和炎症性疾病方面的潜力。
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Yale J Biol Med. 2020 Dec 29;93(5):759-763. eCollection 2020 Dec.
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本文引用的文献
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Do the current guidelines for asthma pharmacotherapy encourage over-treatment?当前的哮喘药物治疗指南是否鼓励过度治疗？
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Amlexanox reversed non-alcoholic fatty liver disease through IKKε inhibition of hepatic stellate cell.安米替林通过抑制肝星状细胞的 IKKε 逆转非酒精性脂肪性肝病。
Life Sci. 2019 Dec 15;239:117010. doi: 10.1016/j.lfs.2019.117010. Epub 2019 Oct 28.
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Cyclic GMP-AMP Triggers Asthma in an IL-33-Dependent Manner That Is Blocked by Amlexanox, a TBK1 Inhibitor.环鸟苷酸-腺苷酸触发哮喘的机制是依赖于 IL-33 的，这种作用可以被 TBK1 抑制剂氨来呫诺所阻断。
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Amlexanox attenuates experimental autoimmune encephalomyelitis by inhibiting dendritic cell maturation and reprogramming effector and regulatory T cell responses.氨来呫诺通过抑制树突状细胞成熟和重编程效应器和调节性 T 细胞反应来减轻实验性自身免疫性脑脊髓炎。
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Inhibition of IKKɛ and TBK1 Improves Glucose Control in a Subset of Patients with Type 2 Diabetes.抑制IKKɛ和TBK1可改善部分2型糖尿病患者的血糖控制。
Cell Metab. 2017 Jul 5;26(1):157-170.e7. doi: 10.1016/j.cmet.2017.06.006.
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Phosphorylation of the exocyst protein Exo84 by TBK1 promotes insulin-stimulated GLUT4 trafficking.TBK1对胞外分泌复合体蛋白Exo84的磷酸化作用促进胰岛素刺激的GLUT4转运。
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