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首页> 外文期刊>European Journal of Medicinal Chemistry: Chimie Therapeutique >Agonist and antagonist ligands of toll-like receptors 7 and 8: Ingenious tools for therapeutic purposes
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Agonist and antagonist ligands of toll-like receptors 7 and 8: Ingenious tools for therapeutic purposes

机译：Toll样受体7和8的激动剂和拮抗剂配体：用于治疗目的的巧妙工具

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摘要

The discovery of the TLRs family and more precisely its functions opened a variety of gates to modulate immunological host responses. TLRs 7/8 are located in the endosomal compartment and activate a specific signaling pathway in a MyD88-dependant manner. According to their involvement into various autoimmune, inflammatory and malignant diseases, researchers have designed diverse TLRs 7/8 ligands able to boost or block the inherent signal transduction. These modulators are often small synthetic compounds and most act as agonists and to a much lesser extent as antagonists. Some of them have reached preclinical and clinical trials, and only one has been approved by the FDA and EMA, imiquimod. The key to the success of these modulators probably lies in their combination with other therapies as recently demonstrated. We gather in this review more than 360 scientific publications, reviews and patents, relating the extensive work carried out by researchers on the design of TLRs 7/8 modulators, which are classified firstly by their biological activities (agonist or antagonist) and then by their chemical structures, which total syntheses are not discussed here. This review also reports about 90 clinical cases, thereby showing the biological interest of these modulators in multiple pathologies. (c) 2020 Elsevier Masson SAS. All rights reserved.
机译：发现TLRS系列的发现，更确切地说，其功能打开了各种栅极来调节免疫主体反应。 TLRS 7/8位于内体隔室中，以MyD88依赖性方式激活特定的信号通路。根据他们参与各种自身免疫性，炎症和恶性疾病，研究人员设计了能够提升或阻止固有信号转导的多样化TLRS 7/8配体。这些调节剂通常是小的合成化合物，大多数作为激动剂和程度更大的程度为拮抗剂。其中一些已达到临床前和临床试验，只有一个已获得FDA和EMA，Imiquimod批准。这些调制器成功的关键可能与最近展示的其他疗法相结合。我们聚集在这条360余科学出版物，审查和专利，通过相关研究人员的TLR 7/8调制器，这是由它们的生物活性（激动剂或拮抗剂）首先分类的设计进行了大量的工作，然后由他们的这里没有讨论总合成的化学结构。该评价还报告了约90例临床病例，从而显示了多种病理中这些调节剂的生物学兴趣。 （c）2020 Elsevier Masson SAS。版权所有。

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