{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T17:00:36Z","timestamp":1791910836586,"version":"4.3.4"},"reference-count":216,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,2,10]],"date-time":"2021-02-10T00:00:00Z","timestamp":1612915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007074","name":"Fondazione CON IL SUD","doi-asserted-by":"publisher","award":["2018-PDR-00799"],"award-info":[{"award-number":["2018-PDR-00799"]}],"id":[{"id":"10.13039\/501100007074","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>For decades, disintegrin and metalloproteinase 17 (ADAM17) has been the object of deep investigation. Since its discovery as the tumor necrosis factor convertase, it has been considered a major drug target, especially in the context of inflammatory diseases and cancer. Nevertheless, the development of drugs targeting ADAM17 has been harder than expected. This has generally been due to its multifunctionality, with over 80 different transmembrane proteins other than tumor necrosis factor \u03b1 (TNF) being released by ADAM17, and its structural similarity to other metalloproteinases. This review provides an overview of the different roles of ADAM17 in disease and the effects of its ablation in a number of in vivo models of pathological conditions. Furthermore, here, we comprehensively encompass the approaches that have been developed to accomplish ADAM17 selective inhibition, from the newest non-zinc-binding ADAM17 synthetic inhibitors to the exploitation of iRhom2 to specifically target ADAM17 in immune cells.<\/jats:p>","DOI":"10.3390\/molecules26040944","type":"journal-article","created":{"date-parts":[[2021,2,12]],"date-time":"2021-02-12T16:12:10Z","timestamp":1613146330000},"page":"944","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":113,"title":["Strategies to Target ADAM17 in Disease: From Its Discovery to the iRhom Revolution"],"prefix":"10.3390","volume":"26","author":[{"given":"Matteo","family":"Calligaris","sequence":"first","affiliation":[{"name":"Proteomics Group of Fondazione Ri.MED, Research Department IRCCS ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), Via E. Tricomi 5, 90145 Palermo, Italy"},{"name":"Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doretta","family":"Cuffaro","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Bonelli","sequence":"additional","affiliation":[{"name":"Proteomics Group of Fondazione Ri.MED, Research Department IRCCS ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), Via E. Tricomi 5, 90145 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donatella Pia","family":"Span\u00f2","sequence":"additional","affiliation":[{"name":"Universit\u00e0 degli Studi di Palermo, STEBICEF (Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche), Viale delle Scienze Ed. 16, 90128 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6795-8091","authenticated-orcid":false,"given":"Armando","family":"Rossello","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2669-5376","authenticated-orcid":false,"given":"Elisa","family":"Nuti","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone Dario","family":"Scilabra","sequence":"additional","affiliation":[{"name":"Proteomics Group of Fondazione Ri.MED, Research Department IRCCS ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), Via E. Tricomi 5, 90145 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e99456","DOI":"10.15252\/embj.201899456","article-title":"Proteolytic ectodomain shedding of membrane proteins in mammals\u2014hardware, concepts, and recent developments","volume":"37","author":"Lichtenthaler","year":"2018","journal-title":"EMBO J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/nrc2628","article-title":"Tumour necrosis factor and cancer","volume":"9","author":"Balkwill","year":"2009","journal-title":"Nat. Rev. Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1038\/nrrheum.2009.181","article-title":"Anti-TNF biologic agents: Still the therapy of choice for rheumatoid arthritis","volume":"5","author":"Taylor","year":"2009","journal-title":"Nat. Rev. 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