State Key Laboratory of Natural Medicines, and Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China.
Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
Expert Opin Ther Pat. 2021 Jun;31(6):563-584. doi: 10.1080/13543776.2021.1877660. Epub 2021 Mar 2.
Stimulator of interferon genes (STING) is a transmembrane protein that localizes in the endoplasmic reticulum. As a crucial adaptor protein in the pathway of sensing cytosolic DNA, STING can regulate innate immune response by inducing the secretion of type Ι interferons and other cytokines after recognizing endogenous or exogenous DNA. Due to the key role of STING in the innate immune system, activation of the STING signaling pathway is expected to be an efficacious immunotherapeutic tactic for cancer and infectious diseases caused by pathogens.
This review summarizes the structures and biological activities of STING agonists published from 2008 to present, the progress in its structural modification of STING agonists, and the development of their clinical study.
STING is an important adaptor protein in the process of triggering the innate immune response to viral infection. So far, substantial STING agonists and inhibitors have been published, and their viable curative effects for diverse diseases prove that STING is a promising therapeutic target.
干扰素基因刺激物(STING)是一种定位于内质网的跨膜蛋白。作为细胞溶质 DNA 感应途径中的关键衔接蛋白,STING 在识别内源性或外源性 DNA 后,通过诱导Ⅰ型干扰素和其他细胞因子的分泌来调节先天免疫反应。由于 STING 在先天免疫系统中的关键作用,激活 STING 信号通路有望成为治疗癌症和病原体引起的传染病的有效免疫治疗策略。
本综述总结了 2008 年至今发表的 STING 激动剂的结构和生物学活性、其 STING 激动剂结构修饰的进展以及其临床研究的进展。
STING 是触发病毒感染先天免疫反应过程中的一个重要衔接蛋白。到目前为止,已经发表了大量的 STING 激动剂和抑制剂,它们对多种疾病的有效疗效证明 STING 是一个有前途的治疗靶点。