Chemical regulation of the cGAS-STING pathway

Abstract

Nucleic acids represent a major class of pathogen and damage signatures, recognized by a variety of host sensors to initiate signaling cascades and immune responses, such as mechanisms of RLR-MAVS, cGAS-STING, TLR-TRIF, and AIM2 inflammasome. Yet, an outstanding challenge is understanding how nucleic acid sensing initiates immune responses and its tethering in various infectious, cancerous, autoimmune, and inflammatory diseases. However, the discovery and application of a plethora of small molecule compounds have substantially facilitated this process. This review provides an overview and recent development of the innate DNA-sensing pathway of cGAS-STING and highlights the multiple agonists and inhibitors in fine-tuning the pathway that can be exploited to improve disease treatment, focusing primarily on crucial pathway components and regulators.

Keywords: Agonist; Antitumor immunity; Compounds; Drug discovery; Inflammation; Innate immune response; Mechanism of disease; RLR-MAVS; TBK1; cGAS-STING.