STING inhibitors target the cyclic dinucleotide binding pocket

Abstract

Significance cGAS (cytosolic DNA sensor cyclic AMP-GMP synthase)-STING (stimulator of interferon genes) signaling is critical for sensing cytosolic DNA to initiate host immune responses against invading pathogens and cancer. However, inappropriate activation of STING signaling causes severe and often fatal autoimmune or autoinflammatory diseases. Hence, STING is an attractive drug target for the treatment of STING-driven autoimmune and inflammatory disorders. Therefore, there is a need to identify lead compounds that effectively inhibit human STING for further drug development. Here, we identified and characterized a STING-specific inhibitor SN-011 with high efficiency, specificity, and safety, paving the way for therapeutically manipulating STING-mediated clinical diseases.