{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,14]],"date-time":"2026-11-14T06:45:19Z","timestamp":1794638719100,"version":"4.9.1"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"7713","license":[{"start":{"date-parts":[[2018,7,1]],"date-time":"2018-07-01T00:00:00Z","timestamp":1530403200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nature"],"published-print":{"date-parts":[[2018,7]]},"DOI":"10.1038\/s41586-018-0287-8","type":"journal-article","created":{"date-parts":[[2018,7,3]],"date-time":"2018-07-03T11:44:17Z","timestamp":1530618257000},"page":"269-273","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1188,"title":["Targeting STING with covalent small-molecule inhibitors"],"prefix":"10.1038","volume":"559","author":[{"given":"Simone M.","family":"Haag","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammet F.","family":"Gulen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc","family":"Reymond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoine","family":"Gibelin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Abrami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexiane","family":"Decout","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Heymann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. Gisou","family":"van der Goot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerardo","family":"Turcatti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rayk","family":"Behrendt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Ablasser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,7,4]]},"reference":[{"key":"287_CR1","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1038\/nature08476","volume":"461","author":"H Ishikawa","year":"2009","unstructured":"Ishikawa, H., Ma, Z. & Barber, G. N. STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity. Nature 461, 788\u2013792 (2009).","journal-title":"Nature"},{"key":"287_CR2","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1126\/science.1232458","volume":"339","author":"L Sun","year":"2013","unstructured":"Sun, L., Wu, J., Du, F., Chen, X. & Chen, Z. J. Cyclic GMP\u2013AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science 339, 786\u2013791 (2013).","journal-title":"Science"},{"key":"287_CR3","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1038\/nature10429","volume":"478","author":"DL Burdette","year":"2011","unstructured":"Burdette, D. L. et al. STING is a direct innate immune sensor of cyclic di-GMP. Nature 478, 515\u2013518 (2011).","journal-title":"Nature"},{"key":"287_CR4","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1038\/nature12306","volume":"498","author":"A Ablasser","year":"2013","unstructured":"Ablasser, A. et al. cGAS produces a 2\u2032-5\u2032-linked cyclic dinucleotide second messenger that activates STING. Nature 498, 380\u2013384 (2013).","journal-title":"Nature"},{"key":"287_CR5","doi-asserted-by":"publisher","first-page":"1355","DOI":"10.1016\/j.celrep.2013.05.009","volume":"3","author":"EJ Diner","year":"2013","unstructured":"Diner, E. J. et al. The innate immune DNA sensor cGAS produces a noncanonical cyclic dinucleotide that activates human STING. Cell Reports 3, 1355\u20131361 (2013).","journal-title":"Cell Reports"},{"key":"287_CR6","doi-asserted-by":"publisher","first-page":"1094","DOI":"10.1016\/j.cell.2013.04.046","volume":"153","author":"P Gao","year":"2013","unstructured":"Gao, P. et al. Cyclic [G(2\u2032,5\u2032)pA(3\u2032,5\u2032)p] is the metazoan second messenger produced by DNA-activated cyclic GMP\u2013AMP synthase. Cell 153, 1094\u20131107 (2013).","journal-title":"Cell"},{"key":"287_CR7","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1126\/science.1229963","volume":"339","author":"J Wu","year":"2013","unstructured":"Wu, J. et al. Cyclic GMP\u2013AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA. Science 339, 826\u2013830 (2013).","journal-title":"Science"},{"key":"287_CR8","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1016\/j.molcel.2013.05.022","volume":"51","author":"X Zhang","year":"2013","unstructured":"Zhang, X. et al. Cyclic GMP\u2013AMP containing mixed phosphodiester linkages is an endogenous high-affinity ligand for STING. Mol. Cell 51, 226\u2013235 (2013).","journal-title":"Mol. Cell"},{"key":"287_CR9","doi-asserted-by":"publisher","first-page":"5328","DOI":"10.1128\/JVI.00037-14","volume":"88","author":"T Abe","year":"2014","unstructured":"Abe, T. & Barber, G. N. Cytosolic-DNA-mediated, STING-dependent proinflammatory gene induction necessitates canonical NF-\u03baB activation through TBK1. J. Virol. 88, 5328\u20135341 (2014).","journal-title":"J. Virol."},{"key":"287_CR10","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1038\/nri3921","volume":"15","author":"GN Barber","year":"2015","unstructured":"Barber, G. N. STING: infection, inflammation and cancer. Nat. Rev. Immunol. 15, 760\u2013770 (2015).","journal-title":"Nat. Rev. Immunol."},{"key":"287_CR11","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.immuni.2011.11.018","volume":"36","author":"A Gall","year":"2012","unstructured":"Gall, A. et al. Autoimmunity initiates in nonhematopoietic cells and progresses via lymphocytes in an interferon-dependent autoimmune disease. Immunity 36, 120\u2013131 (2012).","journal-title":"Immunity"},{"key":"287_CR12","doi-asserted-by":"publisher","first-page":"5516","DOI":"10.1172\/JCI79100","volume":"124","author":"N Jeremiah","year":"2014","unstructured":"Jeremiah, N. et al. Inherited STING-activating mutation underlies a familial inflammatory syndrome with lupus-like manifestations. J. Clin. Invest. 124, 5516\u20135520 (2014).","journal-title":"J. Clin. Invest."},{"key":"287_CR13","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1056\/NEJMoa1312625","volume":"371","author":"Y Liu","year":"2014","unstructured":"Liu, Y. et al. Activated STING in a vascular and pulmonary syndrome. N. Engl. J. Med. 371, 507\u2013518 (2014).","journal-title":"N. Engl. J. Med."},{"key":"287_CR14","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1038\/nri3850","volume":"15","author":"YJ Crow","year":"2015","unstructured":"Crow, Y. J. & Manel, N. Aicardi\u2013Gouti\u00e8res syndrome and the type I interferonopathies. Nat. Rev. Immunol. 15, 429\u2013440 (2015).","journal-title":"Nat. Rev. Immunol."},{"key":"287_CR15","doi-asserted-by":"publisher","first-page":"19386","DOI":"10.1073\/pnas.1215006109","volume":"109","author":"J Ahn","year":"2012","unstructured":"Ahn, J., Gutman, D., Saijo, S. & Barber, G. N. STING manifests self DNA-dependent inflammatory disease. Proc. Natl Acad. Sci. USA 109, 19386\u201319391 (2012).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"287_CR16","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6166","volume":"5","author":"J Ahn","year":"2014","unstructured":"Ahn, J. et al. Inflammation-driven carcinogenesis is mediated through STING. Nat. Commun. 5, 5166 (2014).","journal-title":"Nat. Commun."},{"key":"287_CR17","doi-asserted-by":"publisher","first-page":"800","DOI":"10.1002\/art.40002","volume":"69","author":"J An","year":"2017","unstructured":"An, J. et al. Expression of cyclic GMP\u2013AMP synthase in patients with systemic lupus erythematosus. Arthritis Rheumatol. 69, 800\u2013807 (2017).","journal-title":"Arthritis Rheumatol."},{"key":"287_CR18","doi-asserted-by":"publisher","first-page":"1481","DOI":"10.1038\/nm.4428","volume":"23","author":"KR King","year":"2017","unstructured":"King, K. R. et al. IRF3 and type I interferons fuel a fatal response to myocardial infarction. Nat. Med. 23, 1481\u20131487 (2017).","journal-title":"Nat. Med."},{"key":"287_CR19","doi-asserted-by":"publisher","first-page":"eaan5689","DOI":"10.1126\/scitranslmed.aan5689","volume":"9","author":"L Zeng","year":"2017","unstructured":"Zeng, L. et al. ALK is a therapeutic target for lethal sepsis. Sci. Transl. Med. 9, eaan5689 (2017).","journal-title":"Sci. Transl. Med."},{"key":"287_CR20","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1038\/nm.4450","volume":"24","author":"N Kerur","year":"2018","unstructured":"Kerur, N. et al. cGAS drives noncanonical-inflammasome activation in age-related macular degeneration. Nat. Med. 24, 50\u201361 (2018).","journal-title":"Nat. Med."},{"key":"287_CR21","doi-asserted-by":"publisher","first-page":"1440","DOI":"10.1038\/emboj.2013.86","volume":"32","author":"T Cavlar","year":"2013","unstructured":"Cavlar, T., Deimling, T., Ablasser, A., Hopfner, K. P. & Hornung, V. Species-specific detection of the antiviral small-molecule compound CMA by STING. EMBO J. 32, 1440\u20131450 (2013).","journal-title":"EMBO J."},{"key":"287_CR22","doi-asserted-by":"publisher","first-page":"5216","DOI":"10.4049\/jimmunol.1300097","volume":"190","author":"J Conlon","year":"2013","unstructured":"Conlon, J. et al. Mouse, but not human STING, binds and signals in response to the vascular disrupting agent 5,6-dimethylxanthenone-4-acetic acid. J. Immunol. 190, 5216\u20135225 (2013).","journal-title":"J. Immunol."},{"key":"287_CR23","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1021\/tx050312l","volume":"19","author":"MK Dennehy","year":"2006","unstructured":"Dennehy, M. K., Richards, K. A., Wernke, G. R., Shyr, Y. & Liebler, D. C. Cytosolic and nuclear protein targets of thiol-reactive electrophiles. Chem. Res. Toxicol. 19, 20\u201329 (2006).","journal-title":"Chem. Res. Toxicol."},{"key":"287_CR24","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1038\/nature09472","volume":"468","author":"E Weerapana","year":"2010","unstructured":"Weerapana, E. et al. Quantitative reactivity profiling predicts functional cysteines in proteomes. Nature 468, 790\u2013795 (2010).","journal-title":"Nature"},{"key":"287_CR25","doi-asserted-by":"publisher","first-page":"20842","DOI":"10.1073\/pnas.0911267106","volume":"106","author":"T Saitoh","year":"2009","unstructured":"Saitoh, T. et al. Atg9a controls dsDNA-driven dynamic translocation of STING and the innate immune response. Proc. Natl Acad. Sci. USA 106, 20842\u201320846 (2009).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"287_CR26","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11932","volume":"7","author":"K Mukai","year":"2016","unstructured":"Mukai, K. et al. Activation of STING requires palmitoylation at the Golgi. Nat. Commun. 7, 11932 (2016).","journal-title":"Nat. Commun."},{"key":"287_CR27","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1016\/j.cell.2008.06.032","volume":"134","author":"DB Stetson","year":"2008","unstructured":"Stetson, D. B., Ko, J. S., Heidmann, T. & Medzhitov, R. Trex1 prevents cell-intrinsic initiation of autoimmunity. Cell 134, 587\u2013598 (2008).","journal-title":"Cell"},{"key":"287_CR28","doi-asserted-by":"publisher","first-page":"E5699","DOI":"10.1073\/pnas.1516465112","volume":"112","author":"D Gao","year":"2015","unstructured":"Gao, D. et al. Activation of cyclic GMP\u2013AMP synthase by self-DNA causes autoimmune diseases. Proc. Natl Acad. Sci. USA 112, E5699\u2013E5705 (2015).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"287_CR29","doi-asserted-by":"publisher","first-page":"1939","DOI":"10.4049\/jimmunol.1500969","volume":"195","author":"EE Gray","year":"2015","unstructured":"Gray, E. E., Treuting, P. M., Woodward, J. J. & Stetson, D. B. Cutting edge: cGAS is required for lethal autoimmune disease in the Trex1-deficient mouse model of Aicardi\u2013Gouti\u00e8res Syndrome. J. Immunol. 195, 1939\u20131943 (2015).","journal-title":"J. Immunol."},{"key":"287_CR30","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1038\/nature12640","volume":"503","author":"A Ablasser","year":"2013","unstructured":"Ablasser, A. et al. Cell intrinsic immunity spreads to bystander cells via the intercellular transfer of cGAMP. Nature 503, 530\u2013534 (2013).","journal-title":"Nature"},{"key":"287_CR31","doi-asserted-by":"publisher","first-page":"6719","DOI":"10.1128\/MCB.24.15.6719-6727.2004","volume":"24","author":"M Morita","year":"2004","unstructured":"Morita, M. et al. Gene-targeted mice lacking the Trex1 (DNase III) 3\u2032\u21925\u2032 DNA exonuclease develop inflammatory myocarditis. Mol. Cell. Biol. 24, 6719\u20136727 (2004).","journal-title":"Mol. Cell. Biol."},{"key":"287_CR32","doi-asserted-by":"publisher","first-page":"2157","DOI":"10.4049\/jimmunol.1600722","volume":"197","author":"K Peschke","year":"2016","unstructured":"Peschke, K. et al. Loss of Trex1 in dendritic cells is sufficient to trigger systemic autoimmunity. J. Immunol. 197, 2157\u20132166 (2016).","journal-title":"J. Immunol."},{"key":"287_CR33","doi-asserted-by":"publisher","first-page":"3123","DOI":"10.1093\/bioinformatics\/btx337","volume":"33","author":"V Gardeux","year":"2017","unstructured":"Gardeux, V., David, F. P. A., Shajkofci, A., Schwalie, P. C. & Deplancke, B. ASAP: a web-based platform for the analysis and interactive visualization of single-cell RNA-seq data. Bioinformatics 33, 3123\u20133125 (2017).","journal-title":"Bioinformatics"}],"container-title":["Nature"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/s41586-018-0287-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41586-018-0287-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41586-018-0287-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,20]],"date-time":"2023-05-20T17:47:24Z","timestamp":1684604844000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41586-018-0287-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,7]]},"references-count":33,"journal-issue":{"issue":"7713","published-print":{"date-parts":[[2018,7]]}},"alternative-id":["287"],"URL":"https:\/\/doi.org\/10.1038\/s41586-018-0287-8","relation":{},"ISSN":["0028-0836","1476-4687"],"issn-type":[{"value":"0028-0836","type":"print"},{"value":"1476-4687","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,7]]},"assertion":[{"value":"8 September 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 May 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 July 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A.A. is a consultant to IFM Therapeutics, LLC. A.A., S.M.H., L.R. and the EPFL have filed provisional patent applications related to STING inhibitors. All other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}