刺
化学
小分子
干扰素基因刺激剂
先天免疫系统
信号转导衔接蛋白
生物化学
信号转导
受体
工程类
航空航天工程
作者
David C. Pryde,Sandip Middya,Monali Banerjee,Ritesh Shrivastava,Sourav Basu,Rajib Ghosh,Dharmendra B. Yadav,Arjun Surya
标识
DOI:10.1016/j.ejmech.2020.112869
摘要
The adaptor protein STING plays a major role in innate immune sensing of cytosolic nucleic acids, by triggering a robust interferon response. Despite the importance of this protein as a potential therapeutic target for serious unmet medical conditions including cancer and infectious disease there remains a paucity of STING ligands. Starting with a benzothiazinone series of weak STING activators (human EC50 ∼10 μM) we identified several chemotypes with sub-micromolar STING activity across all the major protein polymorphs. An example compound 53 based on an oxindole core structure demonstrated robust on-target functional activation of STING (human EC50 185 nM) in immortalised and primary cells and a cytokine induction fingerprint consistent with STING activation. Our study has identified several related series of potent small molecule human STING activators with potential to be developed as immunomodulatory therapeutics.
科研通智能强力驱动
Strongly Powered by AbleSci AI