Department of Chemistry and Biochemistry and the BioFrontiers Institute, 596 University of Colorado at Boulder, Boulder, CO 80309-0596, USA.
Chem Soc Rev. 2013 Jun 21;42(12):4859-66. doi: 10.1039/c3cs60039d.
Toll-like receptors (TLRs) are type I transmembrane proteins that are key regulators of both innate and adaptive immune responses. To protect the host from viral and bacterial threats, TLRs trigger a pro-inflammatory immune response by detecting pathogen and danger associated molecular patterns. Considerable evidence has accumulated to show that the dysregulation of TLR signaling contributes to the development and progression of numerous diseases. Therefore, TLRs are emerging as important drug discovery targets. Currently, there is great interest in the development of TLR small molecule modulators for interrogating TLR signaling and treating diseases caused by TLR signaling malfunctions. In this tutorial review, we will outline methods for the discovery of TLR small molecule modulators and the up-to-date progress in this field. Small molecules targeting TLRs not only provide an opportunity to identify promising drug candidates, but also unveil knowledge regarding TLR signaling pathways.
toll 样受体 (TLRs) 是一类 I 型跨膜蛋白，是固有和适应性免疫反应的关键调节因子。为了保护宿主免受病毒和细菌的威胁，TLRs 通过检测病原体和危险相关分子模式触发促炎免疫反应。大量证据表明，TLR 信号转导的失调导致许多疾病的发生和发展。因此，TLRs 正在成为重要的药物发现靶点。目前，人们对开发 TLR 小分子调节剂以研究 TLR 信号转导和治疗 TLR 信号转导功能障碍引起的疾病产生了浓厚的兴趣。在本教程综述中，我们将概述 TLR 小分子调节剂的发现方法和该领域的最新进展。靶向 TLR 的小分子不仅为鉴定有前途的药物候选物提供了机会，也揭示了 TLR 信号通路的相关知识。
