{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T07:09:44Z","timestamp":1778828984088,"version":"3.51.4"},"reference-count":25,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T00:00:00Z","timestamp":1762041600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T00:00:00Z","timestamp":1762041600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004731","name":"Zhejiang Natural Science Foundation","doi-asserted-by":"publisher","award":["LY21H300003"],"award-info":[{"award-number":["LY21H300003"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemistryOpen"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:p>\n                    Although histone deacetylase (HDAC) inhibitors have demonstrated significant advantages in the field of targeted cancer therapy, numerous adverse events have been observed due to the high doses required to achieve therapeutic effects. Additionally, acquired drug resistance to HDAC inhibitors has also been observed in clinical usage. Given these findings, the development of HDAC degraders may represent a more promising strategy to overcome these limitations due to their specific mechanism of action. In this study, 14 HDAC degraders featuring a polyamine linker are designed and synthesized by conjugating HDAC inhibitors (HDACi, Vorinostat) with Cereblon (CRBN, an E3 ubiquitin ligase ligand). Significantly, compound\n                    <jats:bold>I<\/jats:bold>\n                    exhibited a degradation efficiency of \u224862% at 5\u2009\u03bcM in MDA\u2010MB\u2010231 cells. Additionally, compound\n                    <jats:bold>N<\/jats:bold>\n                    exhibited the highest cellular uptake efficiency in a dose\u2010 and time\u2010dependent manner. The findings presented in our manuscript provided valuable insights for the development of a proteolysis targeting chimera with high cellular uptake efficiency.\n                  <\/jats:p>","DOI":"10.1002\/open.202500356","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T07:06:52Z","timestamp":1762153612000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Design and Synthesis of Polyamine\u2010Proteolysis Targeting Chimera Conjugates for Histone Deacetylase (HDAC) Degradation with Enhanced Cellular Uptake"],"prefix":"10.1002","volume":"15","author":[{"given":"Yanran","family":"Liu","sequence":"first","affiliation":[{"name":"Hangzhou Medical College  Hangzhou 311399 P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wentian","family":"Chen","sequence":"additional","affiliation":[{"name":"Hangzhou Medical College  Hangzhou 311399 P. R. 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