干扰素基因刺激剂
刺
化学
兴奋剂
免疫系统
背景(考古学)
免疫疗法
药理学
癌症免疫疗法
干扰素
小分子
内部收益率3
癌症研究
免疫学
先天免疫系统
受体
医学
生物化学
生物
古生物学
航空航天工程
工程类
作者
M. Zhao,Weizhen Fan,Ying Wang,Pengfei Qiang,Zhihua Zheng,Hong Shan,Ming Zhang,Pengyutian Liu,Yao Wang,Guofeng Li,Min Li,Hong Liu
标识
DOI:10.1016/j.ejmech.2023.116018
摘要
In the context of antitumor immune responses, the activation of the stimulator of interferon genes (STING) assumes a critical role and imparts enhanced immunogenicity. An effective strategy for exogenously activating the immune system involves the utilization of STING agonists, and prior investigations primarily concentrated on modifying endogenous cyclic dinucleotides (CDNs) to achieve this. Nevertheless, the practical utility of CDNs was restricted due to limitations associated with their physicochemical attributes and administration protocols. In this article, we present the discovery of a novel small-molecule agonist denoted as M335, identified through high-throughput screening using surface plasmon resonance (SPR). M335 demonstrates the ability to activate the TBK1-IRF3-IFN axis in a STING-dependent manner in vitro. Through experimentation on mouse models bearing tumors, we observed that the administration of M335 resulted in the activation of immune cells. Notably, significant antitumor effects were achieved with both intratumoral and intraperitoneal administration of M335. These findings suggest the potential of M335 as a promising agent for cancer immunotherapy, thereby advancing the field of STING agonists for antitumor applications.
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