{"doi":"10.1073/pnas.2305420120","title":"Targeting STING oligomerization with small-molecule inhibitors","abstract":"Stimulator of interferon genes (STING) is an essential adaptor protein required for the inflammatory response to cytosolic DNA. dsDNA activates cGAS to generate cGAMP, which binds and activates STING triggering a conformational change, oligomerization, and the IRF3- and NFκB-dependent transcription of type I Interferons (IFNs) and inflammatory cytokines, as well as the activation of autophagy. Aberrant activation of STING is now linked to a growing number of both rare as well as common chronic inflammatory diseases. Here, we identify and characterize a potent small-molecule inhibitor of STING. This compound, BB-Cl-amidine inhibits STING signaling and production of type I IFNs, IFN-stimulated genes (ISGs) and NFκB-dependent cytokines, but not other pattern recognition receptors. In vivo, BB-Cl-amidine alleviated pathology resulting from accrual of cytosolic DNA in Trex-1 mutant mice. Mechanistically BB-Cl-amidine inhibited STING oligomerization through modification of Cys 148 . Collectively, our work uncovers an approach to inhibit STING activation and highlights the potential of this strategy for the treatment of STING-driven inflammatory diseases.","journal":"Proceedings of the National Academy of Sciences","year":2023,"id":317638,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":75,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9568,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":109676,"name":"Liraz Shmuel-Galia","orcid":"0000-0002-7502-8062","position":1,"is_corresponding":false},{"id":109682,"name":"Zhaozhao Jiang","orcid":"0000-0002-9768-8491","position":2,"is_corresponding":false},{"id":1023807,"name":"Jeffrey Y. Zhou","orcid":"0000-0002-3683-3448","position":3,"is_corresponding":false},{"id":1023808,"name":"Leonard Barasa","orcid":"0009-0000-4519-0125","position":4,"is_corresponding":false},{"id":457123,"name":"Santanu Mondal","orcid":"0000-0002-7399-8364","position":5,"is_corresponding":false},{"id":109681,"name":"Ruth Wilson","orcid":"0000-0002-2477-2027","position":6,"is_corresponding":false},{"id":532121,"name":"Nadia Sultana","orcid":"0000-0001-8627-101X","position":7,"is_corresponding":false},{"id":109685,"name":"Scott A. Shaffer","orcid":"0000-0002-5264-3257","position":8,"is_corresponding":false},{"id":1024674,"name":"Sze‐Ling Ng","orcid":null,"position":9,"is_corresponding":false},{"id":1023809,"name":"G. Scott Pesiridis","orcid":"0000-0003-1315-6453","position":10,"is_corresponding":false},{"id":109690,"name":"Paul R. Thompson","orcid":"0000-0002-1621-3372","position":11,"is_corresponding":false},{"id":109691,"name":"Katherine A. Fitzgerald","orcid":"0000-0003-3175-609X","position":12,"is_corresponding":false},{"id":109675,"name":"Fiachra Humphries","orcid":"0000-0003-0216-5776","position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":null,"created_at":"2026-07-19T01:06:55.884740Z","pmid":"37549268","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}