Medicinal chemistry perspective on cGAS-STING signaling pathway with small molecule inhibitors

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway serves as a pivotal mediator of innate immunity by triggering the secretion of type I interferons and other proinflammatory cytokines. In view of the immune-related diseases caused by abnormal activity of the cGAS-STING signaling pathway, considerable progress in this field has encouraged the discovery of cGAS-STING inhibitors in the past five years. In this review, we will focus on the link between the cGAS-STING signaling pathway and autoimmune and inflammatory disorders, summarize the development and optimization of cGAS-STING signaling pathway inhibitors, discuss the therapeutic effects on inflammatory diseases and propose suggestions and insights for future exploitation.