兴奋剂
TLR7型
先天免疫系统
炎症
Toll样受体
化学
免疫系统
伤亡人数
信号转导
炎症反应
TLR3型
计算生物学
受体
生物
细胞生物学
免疫学
生物化学
作者
Yi Yang,Adam Csakai,Shuangshuang Jiang,Clark M. Smith,Hiromi Tanji,Jian Huang,Tony E. Jones,Kentaro Sakaniwa,Lindsey J. Broadwell,Chengrui Shi,Subada Soti,Umeharu Ohto,Yaohui Fang,Shū Shěn,Fei Deng,Toshiyuki Shimizu,Hang Yin
标识
DOI:10.1038/s41467-021-24536-4
摘要
Abstract Small-molecule modulators of TLR8 have drawn much interests as it plays pivotal roles in the innate immune response to single-stranded RNAs (ssRNAs) derived from viruses. However, their clinical uses are limited because they can invoke an uncontrolled, global inflammatory response. The efforts described herein culminate in the fortuitous discovery of a tetrasubstituted imidazole CU-CPD107 which inhibits R848-induced TLR8 signaling. In stark contrast, CU-CPD107 shows unexpected synergistic agonist activities in the presence of ssRNA, while CU-CPD107 alone is unable to influence TLR8 signaling. CU-CPD107 ’s unique, dichotomous behavior sheds light on a way to approach TLR agonists. CU-CPD107 offers the opportunity to avoid the undesired, global inflammation side effects that have rendered imidazoquinolines clinically irrelevant, providing an insight for the development of antiviral drugs.
科研通智能强力驱动
Strongly Powered by AbleSci AI