Small molecules targeting cGAS-STING pathway for autoimmune disease

Autoimmune diseases represent a class of over 80 illnesses with high incidence and prevalence and share a common pathogenesis of immune system disorders and self-attack. Over the past decade, extensive studies have demonstrated that imbalance of cGAS-STING mediated innate immune signaling is closely involved in autoimmune diseases. Over-activation of cGAS-STING pathway by mutations of STING or several exonucleases can cause accumulation of interferon and systemic inflammation. Therefore, suppression of the upregulated cGAS-STING pathway holds great potential in the treatment of human inflammatory and autoimmune diseases. Inhibitors targeting cGAS, STING and the downstream factors have been developed and pharmacologically evaluated recently. Herein, we summarize the recent advance on development of small molecular inhibitors targeting the key effectors in cGAS-STING axis as promising treatment for autoimmune diseases. [Display omitted] •Autoimmune diseases represent a class of over 80 illnesses with high incidence.•Over-activation of cGAS-STING pathway is implicated in autoimmune diseases.•Mice disease models were built bearing mutations of STING or several exonucleases.•Inhibitors targeting cGAS, STING and the downstream factors have been developed.•Some of these inhibitors showed efficacy in cells and in mice models.