{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T04:25:25Z","timestamp":1764563125990,"version":"3.46.0"},"reference-count":28,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T00:00:00Z","timestamp":1763683200000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    A series of dipeptidic proteasome inhibitors with\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2010lactam as the\n                    <jats:italic>C<\/jats:italic>\n                    \u2010terminus was designed and synthesized. Biochemical evaluations of their effects on chymotrypsin\u2010like (CT\u2010L) activity revealed that some of them had inhibitory activity against the proteasome, with IC\n                    <jats:sub>50<\/jats:sub>\n                    values in the micromolar range. Based on the enzymatic results, structure\u2013activity relationships (SAR) were discussed in detail. Some potent compounds were further selected for antiproliferative assays toward multiple cancer cell lines, with compounds\n                    <jats:bold>66<\/jats:bold>\n                    and\n                    <jats:bold>78<\/jats:bold>\n                    demonstrating activity against RS4;11 cells and IC\n                    <jats:sub>50<\/jats:sub>\n                    values of less than 1\u2009\u03bcM. Additionally, cellular mechanistic studies indicated that these effects were linked to their ability to inhibit proteasome signal pathways and to induce apoptosis in RS4;11 cells, as demonstrated by flow cytometry. Collectively, these results illustrate that compound\n                    <jats:bold>66<\/jats:bold>\n                    is a potent proteasome inhibitor with significant potential as an antitumor agent.\n                  <\/jats:p>","DOI":"10.1002\/ardp.70136","type":"journal-article","created":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T05:01:40Z","timestamp":1763787700000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of Novel\n                    <i>\u03b2<\/i>\n                    \u2010Lactam Derivatives as Proteasome Inhibitors for Antitumor Therapy"],"prefix":"10.1002","volume":"358","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-8931-4316","authenticated-orcid":false,"given":"Yu","family":"Cao","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Preparation Hangzhou Xixi Hospital Hangzhou 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