Bioactive modulators targeting STING adaptor in cGAS-STING pathway

•STING adaptor in cGAS-STING pathway has been identified as an essential therapeutic target.•Recent understanding of STING functioning in regulating immune response.•Recent advances in STING modulator discovery efforts.•Structural basis and characteristics of agonists/antagonists interacting with STING. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING)-pathway triggers innate immune responses by recognizing cytosolic DNA. Recent studies revealed that STING adaptor associates with various diseases, and several modulators targeting STING have been identified including three agonists that have entered clinical trials for treating cancer over the past 2 years. In particular, the efficacy of STING agonists and/or antagonists suggests adaptor STING as a potential therapeutic target for diverse diseases. Herein, we summarize the latest advances in understanding STING functioning and provide an overview of recent STING modulator discoveries, including structural details and the potential therapeutic applications of these modulators.