ABSTRACT
Introduction
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.
Areas covered
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.
Expert opinion
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.
Article highlights
The study of STING agonists has become a hotpot in both academia and industry in recent years. Nowadays, some agonists have entered clinical trials for the treatment of tumors.
In this review, STING agonists (2008-2020) were collected and classified by chemical structures. Simultaneously, the representative compounds and their biological activities were described.
Some lead compounds have been disclosed, and researchers have devised more potent STING agonists based on step-by-step structural optimizations.
Clinical trials of STING agonist monotherapy and combination therapy with immune checkpoint inhibitors, or conventional chemotherapies for the treatment of tumors are highlighted in this preview.
This box summarizes key points contained in the article.
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.