The immune system uses members of the toll‐like receptor (TLR) family to recognize a variety of pathogen‐ and host‐derived molecules in order to initiate immune responses. Although TLR‐mediated, pro‐inflammatory immune responses are essential for host defense, prolonged and exaggerated activation can result in inflammation pathology that manifests in a variety of diseases. Therefore, small‐molecule inhibitors of the TLR signaling pathway might have promise as anti‐inflammatory drugs. We previously identified a class of triaryl pyrazole compounds that inhibit TLR signaling by modulation of the protein–protein interactions essential to the pathway. We have now systematically examined the structural features essential for inhibition of this pathway, revealing characteristics of compounds that inhibited all TLRs tested (pan‐TLR signaling inhibitors) as well as compounds that selectively inhibited certain TLRs. These findings reveal interesting classes of compounds that could be optimized for particular inflammatory diseases governed by different TLRs.

中文翻译：

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三芳基吡唑类收费受体信号抑制剂：控制泛信号和选择性信号抑制剂的结构-活性关系。

免疫系统使用Toll样受体（TLR）家族的成员识别各种病原体和宿主衍生的分子，从而启动免疫反应。尽管TLR介导的促炎性免疫反应对于宿主防御至关重要，但长时间而过度的激活会导致炎症病理，表现为多种疾病。因此，TLR信号通路的小分子抑制剂有望作为抗炎药。我们先前发现了一类三芳基吡唑化合物，可通过调节该途径必不可少的蛋白质间相互作用来抑制TLR信号传导。现在，我们已经系统地研究了抑制该途径必不可少的结构特征，揭示了可抑制所有测试的TLR的化合物（pan-TLR信号抑制剂）以及选择性抑制某些TLR的化合物的特征。这些发现揭示了有趣的化合物类别，可以针对由不同TLR控制的特定炎症疾病进行优化。