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美国食品药品监督管理局批准的药物:Toll样受体4(TLR4)候选药物用于神经病变的重新利用

FDA Approved Drugs Repurposing of Toll-Like Receptor4 (TLR4) Candidate for Neuropathy.

作者信息

Zali Hakimeh, Golchin Ali, Farahani Masoumeh, Yazdani Mohsen, Ranjbar Mohammad Mehdi, Dabbagh Ali

机构信息

Department of Tissue Engineering and Applied Cell, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Proteomics Research Center, Faculty of Paramedical Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

Iran J Pharm Res. 2019 Summer;18(3):1639-1647. doi: 10.22037/ijpr.2019.2394.

Abstract

Accumulating evidence indicates that toll-like receptor 4 (TLR4) plays a critical role in promoting adaptive immune responses and are definitively involved in the expansion and maintenance of the neuropathic pain. Though the application of docking in virtual-screening methods to drug discovery has some challenge, it allows directed and meaningful design of drugs for a target protein; which can lead to low costing approaches with shortcuts; resulting in evolution and discovery of promising new drugs. Nevertheless, in parallel with virtual screening methods, attendant developments in cell culture and studies must be achieved. In the present paper, we aimed to discover new drugs that have the ability to bind and inhibit TLR4 functions. So, after using the Pathway studio to investigate the biological pathways and protein interaction maps between TLR4 and neuropathy, we reported the application of the affinity-based approach of different pharmaceuticals; these agents contained all of the approved drugs; which could bind to Toll-like receptor 4 in blind high-throughput screening. Our results demonstrated that among the primary list of 1945 retrieved compounds, 39 approved compounds could be the right candidate to perform a biological test in different and conditions and as a lead for further neurophysiological and neuropathological studies and treatment of neuropathic pain.

摘要

越来越多的证据表明,Toll样受体4(TLR4)在促进适应性免疫反应中起关键作用,并且确实参与了神经性疼痛的扩展和维持。尽管将对接应用于虚拟筛选方法进行药物发现存在一些挑战,但它允许针对目标蛋白进行有针对性且有意义的药物设计;这可以带来低成本的捷径方法;从而促成有前景的新药的研发和发现。然而,与虚拟筛选方法并行,细胞培养和相关研究也必须取得进展。在本文中,我们旨在发现能够结合并抑制TLR4功能的新药。因此,在使用Pathway studio研究TLR4与神经病变之间的生物途径和蛋白质相互作用图谱后,我们报告了不同药物基于亲和力方法的应用;这些药物包含所有已批准的药物;它们能够在盲法高通量筛选中与Toll样受体4结合。我们的结果表明,在检索到的1945种化合物的初步列表中,39种已批准的化合物可能是在不同条件下进行生物学测试的合适候选物,并可作为进一步神经生理学和神经病理学研究以及治疗神经性疼痛的先导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3600/6934974/f40bdc571bea/ijpr-18-1639-g001.jpg

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