{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:12:01Z","timestamp":1790773921841,"version":"4.1.0"},"reference-count":50,"publisher":"Portland Press Ltd.","issue":"1","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,2,1]]},"abstract":"<jats:p>Proteases play a key role in various pathological processes and several protease inhibitors are already available for treatment. DUBs (deubiquitinating enzymes) constitute one of the largest classes of human proteases and are key effectors of the ubiquitin\u2013proteasome system. This pathway regulating cellular protein turnover has been implicated in the pathogenesis of many human diseases, including neurodegenerative disorders, viral diseases and cancer. The therapeutic efficacy of the proteasome inhibitor Velcade\u00ae (bortezomib) for treating multiple myeloma and mantle cell lymphoma establishes this system as a valid target for cancer treatment. A promising alternative to targeting the proteasome itself would be to target the upstream, ubiquitin conjugation\/deconjugation system, to generate more specific, less toxic anticancer agents. Advances in small molecule-based inhibitors specifically targeting DUBs are presented in this review.<\/jats:p>","DOI":"10.1042\/bst0380137","type":"journal-article","created":{"date-parts":[[2010,1,20]],"date-time":"2010-01-20T16:17:54Z","timestamp":1264004274000},"page":"137-143","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":109,"title":["The therapeutic potential of deubiquitinating enzyme inhibitors"],"prefix":"10.1042","volume":"38","author":[{"given":"Fr\u00e9d\u00e9ric","family":"Colland","sequence":"first","affiliation":[{"name":"Hybrigenics SA, 3-5 Impasse Reille, 75014 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2010,1,19]]},"reference":[{"key":"2021111720260704400_B1","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1152\/physrev.00027.2001","article-title":"The ubiquitin\u2013proteasome proteolytic pathway: destruction for the sake of construction","volume":"82","author":"Glickman","year":"2002","journal-title":"Physiol. 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Natl. Acad. Sci. U.S.A."},{"key":"2021111720260704400_B48","doi-asserted-by":"crossref","first-page":"2286","DOI":"10.1158\/1535-7163.MCT-09-0097","article-title":"Small-molecule inhibitor of USP7\/HAUSP ubiquitin protease stabilizes and activates p53 in cells","volume":"8","author":"Colland","year":"2009","journal-title":"Mol. Cancer Ther."},{"key":"2021111720260704400_B49","unstructured":"Lopez\n              R.\n            \n            \n              Collura\n              V.\n            \n            \n              Sippl\n              W.\n            \n            \n              Colland\n              F.\n            \n          \n          Novel specific inhibitors of ubiquitin specific protease 7, the pharmaceutical compositions thereof and their therapeutic applications\n          Eur. Pat. Application 09305030.0\n          2009"},{"key":"2021111720260704400_B50","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1042\/BJ20080779","article-title":"Positional-scanning fluorigenic substrate libraries reveal unexpected specificity determinants of DUBs (deubiquitinating enzymes)","volume":"415","author":"Drag","year":"2008","journal-title":"Biochem. 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