{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T00:59:36Z","timestamp":1775869176513,"version":"3.50.1"},"reference-count":54,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"vor","delay-in-days":27,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    Quinazolinones have been recently recognized as valuable scaffolds for developing novel therapeutic opportunities. They indeed exhibit structural versatility and a wide range of biological activities, including antifungal, antitubercular, antihypertensive, anticancer, and antiviral ones. In this work, a focused library of new bioactive 4\u2010(3\u2010H)\u2010quinazolinones has been synthesized, their cytotoxic action against DU\u2010145 prostate cancer cells has been detailed, and compound\n                    <jats:bold>4k<\/jats:bold>\n                    has been revealed as the most active one. Consequently, its interactome has been characterized by a label\u2010free functional proteomics\u2010based platform coupling drug affinity responsive target stability (DARTS) and targeted limited proteolysis\u2010multiple reaction monitoring\u2010mass spectrometry (t\u2010LiP\u2010MRM\u2010MS). This multifaced strategy has been employed to reveal few subunits of the 26S proteasome machinery as the most reliable compound\n                    <jats:bold>4k<\/jats:bold>\n                    biological targets. This paved the way for the deepening of the protein\u2013ligand interaction using in\u2009vitro and in silico bio\u2010orthogonal techniques. Finally, the analysis of its function in living DU\u2010145 cells prompted compound\n                    <jats:bold>4k<\/jats:bold>\n                    as a novel quinazolinone\u2010bearing inhibitor of the chymotrypsin\u2010like activity of the proteasomal\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u22125 subunit, stirring this framework for the development of new anticancer drugs.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.202500728","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T22:24:51Z","timestamp":1769639091000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Functional Proteomics of Quinazolin\u20104\u2010One Derivatives Targeting the Proteasome"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7244-0297","authenticated-orcid":false,"given":"Elva","family":"Morretta","sequence":"first","affiliation":[{"name":"Department of Pharmacy University of Naples \u201cFederico II\u201d  Via D. 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