靶向Toll样受体2的小分子调节剂研究进展

Research progress of small molecule modulators targeting Toll-like receptor 2

Toll样受体(Toll-like receptors,TLRs)是最早被发现的天然免疫模式识别受体(pattern-recognition receptors,PRRs)。TLR信号传导通路的异常是导致慢性炎症、癌症、神经系统疾病和心血管疾病等的关键因素,TLR的激动剂和抑制剂的开发都备受关注。目前已知的TLR2激动剂,如脂肽或其衍生物,由于合成困难、易水解、且易引发炎性细胞因子风暴,存在一定的药物研发局限性,抑制剂则少有报道。具有更高稳定性的新型小分子TLR2激动剂或抑制剂将更有可能开发成肿瘤免疫治疗或抗炎药物。

Toll like receptors(TLRs)are the earliest discovered natural immune pattern recognition receptors(PRRs).The abnormality of TLR signal transduction pathway is the key factor leading to chronic inflammatory,cancer,nervous system disease and cardiovascular diseases.The development of TLR agonists and inhibitors has attracted much attention.Currently known TLR2 agonists,such as lipopeptides or their derivatives,have certain limitations in drug development due to their difficult synthesis,easy hydrolysis,and triggering inflammatory cytokine storms,while inhibitors have been rarely reported.New small molecule TLR2 agonists or inhibitors with higher stability are more likely to be developed as tumor immunotherapy or anti-inflammatory drugs.