刺
干扰素基因刺激剂
化学
药理学
体内
干扰素
兴奋剂
药代动力学
癌症免疫疗法
免疫疗法
癌症
受体
先天免疫系统
免疫学
生物化学
医学
生物
内科学
生物技术
航空航天工程
工程类
作者
Xi Feng,Lixia Pan,Zhiyu Qian,Dongyu Liu,Xin‐Yuan Guan,Feng Li,Bin Song,Xi Xu,Ning‐Hua Tan,Yi Ma,Zhiyu Li,Zhe Wang,Jinlei Bian
标识
DOI:10.1021/acs.jmedchem.2c00634
摘要
Activation of the stimulator of interferon genes (STING) pathway to achieve antitumor response is an attractive approach for cancer immunotherapy. In this study, we report the identification of BSP16 (LF250) as a potent, orally available STING agonist. BSP16 strongly activates STING signaling in human and mouse cells and binds STING as a homodimer. A 2.4 Å cocrystal structure revealed that BSP16 could induce the "closed" conformation of STING. In vivo studies revealed that BSP16 is well tolerated, has an excellent pharmacokinetic profile as an oral drug, and induces tumor regression and durable antitumor immunity. The promising bioactivities of BSP16 make it valuable for further development as an antitumor agent.
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