{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T16:00:39Z","timestamp":1792512039638,"version":"4.5.0"},"reference-count":48,"publisher":"The Company of Biologists","issue":"11","license":[{"start":{"date-parts":[[2021,2,11]],"date-time":"2021-02-11T00:00:00Z","timestamp":1613001600000},"content-version":"vor","delay-in-days":102,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100011102","name":"Seventh Framework Programme","doi-asserted-by":"publisher","award":["305564"],"award-info":[{"award-number":["305564"]}],"id":[{"id":"10.13039\/100011102","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,11,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Inflammatory bowel diseases (IBDs) cause significant morbidity and mortality. Aberrant NF-\u03baB signalling is strongly associated with these conditions, and several established drugs influence the NF-\u03baB signalling network to exert their effect. This study aimed to identify drugs that alter NF-\u03baB signalling and could be repositioned for use in IBD. The SysmedIBD Consortium established a novel drug-repurposing pipeline based on a combination of in silico drug discovery and biological assays targeted at demonstrating an impact on NF-\u03baB signalling, and a murine model of IBD. The drug discovery algorithm identified several drugs already established in IBD, including corticosteroids. The highest-ranked drug was the macrolide antibiotic clarithromycin, which has previously been reported to have anti-inflammatory effects in aseptic conditions. The effects of clarithromycin effects were validated in several experiments: it influenced NF-\u03baB-mediated transcription in murine peritoneal macrophages and intestinal enteroids; it suppressed NF-\u03baB protein shuttling in murine reporter enteroids; it suppressed NF-\u03baB (p65) DNA binding in the small intestine of mice exposed to lipopolysaccharide; and it reduced the severity of dextran sulphate sodium-induced colitis in C57BL\/6 mice. Clarithromycin also suppressed NF-\u03baB (p65) nuclear translocation in human intestinal enteroids. These findings demonstrate that in silico drug repositioning algorithms can viably be allied to laboratory validation assays in the context of IBD, and that further clinical assessment of clarithromycin in the management of IBD is required.<\/jats:p>\n                  <jats:p>This article has an associated First Person interview with the joint first authors of the paper.<\/jats:p>","DOI":"10.1242\/dmm.044040","type":"journal-article","created":{"date-parts":[[2020,9,21]],"date-time":"2020-09-21T17:35:17Z","timestamp":1600709717000},"source":"Crossref","is-referenced-by-count":13,"title":["Using systems medicine to identify a therapeutic agent with potential for repurposing in inflammatory bowel disease"],"prefix":"10.1242","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2325-8050","authenticated-orcid":false,"given":"Katie","family":"Lloyd","sequence":"first","affiliation":[{"name":"University of Liverpool 1 Department of Cellular and Molecular Physiology , , Liverpool L69 3GE , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6665-8508","authenticated-orcid":false,"given":"Stamatia","family":"Papoutsopoulou","sequence":"additional","affiliation":[{"name":"University of Liverpool 1 Department of Cellular and Molecular Physiology , , Liverpool L69 3GE , UK"},{"name":"University of Manchester 2 Faculty of Biology, Medicine and Health , , Manchester M13 9PL , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Smith","sequence":"additional","affiliation":[{"name":"University of Manchester 2 Faculty of Biology, Medicine and Health , , Manchester M13 9PL , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1881-8746","authenticated-orcid":false,"given":"Philip","family":"Stegmaier","sequence":"additional","affiliation":[{"name":"geneXplain GmbH 3 , Wolfenbuettel 38302 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francois","family":"Bergey","sequence":"additional","affiliation":[{"name":"LifeGlimmer GmbH 4 , Berlin 12163 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorna","family":"Morris","sequence":"additional","affiliation":[{"name":"LifeGlimmer GmbH 4 , Berlin 12163 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeleine","family":"Kittner","sequence":"additional","affiliation":[{"name":"LifeGlimmer GmbH 4 , Berlin 12163 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8324-614X","authenticated-orcid":false,"given":"Hazel","family":"England","sequence":"additional","affiliation":[{"name":"University of Manchester 2 Faculty of Biology, Medicine and Health , , Manchester M13 9PL , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2502-6787","authenticated-orcid":false,"given":"Dave","family":"Spiller","sequence":"additional","affiliation":[{"name":"University of Manchester 2 Faculty of Biology, Medicine and Health , , Manchester M13 9PL , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3617-3232","authenticated-orcid":false,"given":"Mike H. 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