Introduction: STING is at the center of the cGAS-STING signaling and acts as the hub of the innate immune system. Hyper-activation of STING has been observed in various severe autoimmune diseases, such as AGS, SLE, and many other diseases including neurological and metabolic disorders. Therefore, STING has been considered as a promising target. In recent years, several STING inhibitors have been claimed in patents.
Areas covered: Small-molecule STING inhibitors reported in patents (disclosed before May 2022 through the public database at https://worldwide.espacenet.com) were summarized in this review and the available structure-activity relationships (SARs) and molecular mechanisms of action were presented.
Expert opinion: Compared with STING agonists, the development of STING inhibitors is still in its infancy and no candidates have entered clinical investigation stage. Fortunately, patent applications are appearing at an increasing rate and a few of them have been validated in vivo, thus providing valuable insights for further structural optimization. More efforts are urgently needed since it is not clear yet that inhibitors targeting STING can solely exert sufficient therapeutic effects on autoimmune diseases, and the toxicity profile of such inhibitors is unknown as well. Therefore, it is extremely important to identify a selective and efficacious STING inhibitor for clinical evaluation to provide proof-of-concept for this approach.
Keywords: Autoimmune disease; inhibitors; innate immunity; stimulator of interferon genes (STING); structure–activity relationship (SAR).