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1
Amlexanox: A Novel Therapeutic for Atopic, Metabolic, and Inflammatory Disease.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。
Yale J Biol Med. 2020 Dec 29;93(5):759-763. eCollection 2020 Dec.
2
Amlexanox attenuates LPS-induced neuroinflammatory responses in microglial cells via inhibition of NF-κB and STAT3 signaling pathways.氨来呫诺通过抑制 NF-κB 和 STAT3 信号通路减轻 LPS 诱导的小胶质细胞神经炎症反应。
Sci Rep. 2024 Feb 2;14(1):2744. doi: 10.1038/s41598-024-53235-5.
3
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.
4
Dual TBK1/IKKε inhibitor amlexanox mitigates palmitic acid-induced hepatotoxicity and lipoapoptosis in vitro.双 TBK1/IKKε 抑制剂氨来呫诺能减轻体外棕榈酸诱导的肝毒性和脂肪凋亡。
Toxicology. 2020 Nov;444:152579. doi: 10.1016/j.tox.2020.152579. Epub 2020 Sep 6.
5
Carboxylic Acid Derivatives of Amlexanox Display Enhanced Potency toward TBK1 and IKK and Reveal Mechanisms for Selective Inhibition.Amlexanox 的羧酸衍生物对 TBK1 和 IKK 的活性增强,并揭示了其选择性抑制的机制。
Mol Pharmacol. 2018 Oct;94(4):1210-1219. doi: 10.1124/mol.118.112185. Epub 2018 Aug 6.
6
Dual TBK1/IKKɛ inhibitor amlexanox attenuates the severity of hepatotoxin-induced liver fibrosis and biliary fibrosis in mice.双 TBK1/IKKɛ 抑制剂氨来呫诺能减轻小鼠肝毒素诱导的肝纤维化和胆管纤维化的严重程度。
J Cell Mol Med. 2020 Jan;24(2):1383-1398. doi: 10.1111/jcmm.14817. Epub 2019 Dec 10.
7
Inhibition of TBK1 by amlexanox attenuates paraquat-induced acute lung injury.氨来呫诺对TBK1的抑制作用减轻了百草枯诱导的急性肺损伤。
Toxicology. 2020 Oct;443:152555. doi: 10.1016/j.tox.2020.152555. Epub 2020 Aug 5.
8
Amlexanox exerts anti-inflammatory actions by targeting phosphodiesterase 4B in lipopolysaccharide-activated macrophages.氨来呫诺通过靶向脂多糖激活的巨噬细胞中的磷酸二酯酶 4B 发挥抗炎作用。
Biochim Biophys Acta Mol Cell Res. 2020 Oct;1867(10):118766. doi: 10.1016/j.bbamcr.2020.118766. Epub 2020 Jun 3.
9
The Specific IKKε/TBK1 Inhibitor Amlexanox Suppresses Human Melanoma by the Inhibition of Autophagy, NF-κB and MAP Kinase Pathways.特异性 IKKε/TBK1 抑制剂氨来呫诺通过抑制自噬、NF-κB 和 MAP 激酶通路抑制人黑色素瘤。
Int J Mol Sci. 2020 Jul 2;21(13):4721. doi: 10.3390/ijms21134721.
10
Amlexanox ameliorates acetaminophen-induced acute liver injury by reducing oxidative stress in mice.氨来呫诺通过减少小鼠的氧化应激改善对乙酰氨基酚诱导的急性肝损伤。
Toxicol Appl Pharmacol. 2019 Dec 15;385:114767. doi: 10.1016/j.taap.2019.114767. Epub 2019 Nov 5.

引用本文的文献

1
Amlexanox inhibits production of type I interferon and suppresses B cell differentiation : a possible therapeutic option for systemic lupus erythematosus and other systemic inflammatory diseases.氨来呫诺抑制I型干扰素的产生并抑制B细胞分化:系统性红斑狼疮和其他全身性炎症性疾病的一种可能治疗选择。
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Identification and validation of neutrophil-related biomarkers in acute-on-chronic liver failure.慢性肝衰竭急性发作中性粒细胞相关生物标志物的鉴定与验证
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Amlexanox targeted inhibition of TBK1 regulates immune cell function to exacerbate DSS-induced inflammatory bowel disease.氨来呫诺对TBK1的靶向抑制作用通过调节免疫细胞功能加重葡聚糖硫酸钠诱导的炎症性肠病。
Clin Exp Immunol. 2025 Jan 21;219(1). doi: 10.1093/cei/uxae082.
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TBK1, a prioritized drug repurposing target for amyotrophic lateral sclerosis: evidence from druggable genome Mendelian randomization and pharmacological verification in vitro.TBK1 是肌萎缩侧索硬化症的优先药物重定位靶点:来自可用药基因组 Mendelian 随机化和体外药理学验证的证据。
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Biomolecules. 2023 Jun 14;13(6):988. doi: 10.3390/biom13060988.
6
The TBK1/IKKε inhibitor amlexanox improves dyslipidemia and prevents atherosclerosis.TBK1/IKKε 抑制剂氨来呫诺可改善血脂异常并预防动脉粥样硬化。
JCI Insight. 2022 Sep 8;7(17):e155552. doi: 10.1172/jci.insight.155552.
7
Role of IKKε in the Metabolic Diseases: Physiology, Pathophysiology, and Pharmacology.IKKε在代谢性疾病中的作用:生理学、病理生理学及药理学
Front Pharmacol. 2022 May 19;13:888588. doi: 10.3389/fphar.2022.888588. eCollection 2022.
8
Comprehensive Analysis of the Systemic Transcriptomic Alternations and Inflammatory Response during the Occurrence and Progress of COVID-19.全面分析 COVID-19 发生和进展过程中的系统转录组变化和炎症反应。
Oxid Med Cell Longev. 2021 Aug 26;2021:9998697. doi: 10.1155/2021/9998697. eCollection 2021.

本文引用的文献

1
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?
Expert Opin Pharmacother. 2020 Aug;21(11):1283-1286. doi: 10.1080/14656566.2020.1759551. Epub 2020 May 13.
2
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.
3
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。
Front Immunol. 2019 Sep 26;10:2212. doi: 10.3389/fimmu.2019.02212. eCollection 2019.
4
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。
J Neuroinflammation. 2019 Mar 1;16(1):52. doi: 10.1186/s12974-019-1438-z.
5
Carboxylic Acid Derivatives of Amlexanox Display Enhanced Potency toward TBK1 and IKK and Reveal Mechanisms for Selective Inhibition.Amlexanox 的羧酸衍生物对 TBK1 和 IKK 的活性增强,并揭示了其选择性抑制的机制。
Mol Pharmacol. 2018 Oct;94(4):1210-1219. doi: 10.1124/mol.118.112185. Epub 2018 Aug 6.
6
TBK1 at the Crossroads of Inflammation and Energy Homeostasis in Adipose Tissue.TBK1 在脂肪组织炎症和能量稳态的交汇点。
Cell. 2018 Feb 8;172(4):731-743.e12. doi: 10.1016/j.cell.2018.01.007.
7
Drug Repurposing Patent Applications April-June 2017.2017年4月至6月药物重新利用专利申请
Assay Drug Dev Technol. 2017 Dec;15(8):372-377. doi: 10.1089/adt.2017.29068.pq2.
8
Japanese Guideline for Allergic Rhinitis 2014.《2014年日本变应性鼻炎指南》
Allergol Int. 2014;63(3):357-375. doi: 10.2332/allergolint.14-RAI-0768. Epub 2015 Feb 27.
9
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.
10
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。
Sci Signal. 2017 Mar 21;10(471):eaah5085. doi: 10.1126/scisignal.aah5085.

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.

PMID:33380937
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7757066/
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。