{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T12:42:24Z","timestamp":1792586544773,"version":"4.5.0"},"reference-count":34,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:00:00Z","timestamp":1792540800000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry &amp;amp; Biodiversity"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Pin1 is a peptidyl\u2010prolyl isomerase involved in key signalling pathways and upregulated in different cancers, including Multiple Myeloma (MM), where it is linked to poor prognosis\/drug resistance. Despite its therapeutic relevance, Pin1 remains challenging to target with conventional inhibitors thereby motivating interest in Targeted Protein Degradation (TPD) strategies. All reported Pin1\u2010PROTACs rely on covalent Pin1 ligands, leaving non\u2010covalent degraders largely unexplored. Since PROTACs (PROteolysis TArgeting Chimeras) act catalytically\/reversibly, non\u2010covalent designs are attractive. Here, we describe the design\/synthesis\/evaluation of 12 non\u2010covalent potential Pin1\u2010PROTACs (\n                    <jats:bold>P1<\/jats:bold>\n                    \u2013\n                    <jats:bold>P12<\/jats:bold>\n                    ) based on reversible peptidomimetic ligand and in a prodrug form to allow cell permeability. Despite rational design, stability and measurable target engagement,\n                    <jats:bold>P1<\/jats:bold>\n                    \u2013\n                    <jats:bold>P12<\/jats:bold>\n                    displayed none or very limited degradation activity, with the most active molecule,\n                    <jats:bold>P3<\/jats:bold>\n                    , achieving only 39% of Pin1 depletion in MM cells. To confirm Pin1 degradability in MM, MM1.R cells were treated with the covalent PROTAC\n                    <jats:bold>P1D\u201034<\/jats:bold>\n                    , which induced robust dose\u2010dependent degradation (DC\n                    <jats:sub>50<\/jats:sub>\n                    \u00a0=\u00a03.16\u00a0\u00b5M,\u00a0D\n                    <jats:sub>MAX<\/jats:sub>\n                    =\u00a090%). Overall, while demonstrating the feasibility of Pin1 depletion\u00a0in MM, this work highlights the challenge of achieving effective Pin1 degradation with non\u2010covalent micromolar ligands, underscores the current advantage of covalent engagement, and provides a foundation for the future development of non\u2010covalent Pin1 degraders.\n                  <\/jats:p>","DOI":"10.1002\/cbdv.71850","type":"journal-article","created":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T11:58:59Z","timestamp":1792583939000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring Non\u2010Covalent Pin1\u2010PROTACs Insights Into Degradation Efficiency in Multiple Myeloma Cell Line"],"prefix":"10.1002","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-5054-1335","authenticated-orcid":false,"given":"Lorenzo","family":"Meneghelli","sequence":"first","affiliation":[{"name":"CNRS BioCIS CY Cergy Paris 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Universit\u00e9 Paris\u2010Saclay  Orsay France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0748-0284","authenticated-orcid":false,"given":"Simon","family":"Nadal","sequence":"additional","affiliation":[{"name":"CNRS BioCIS CY Cergy Paris Universit\u00e9  Cergy Pontoise France"},{"name":"CNRS BioCIS Universit\u00e9 Paris\u2010Saclay  Orsay France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delphine","family":"Ravault","sequence":"additional","affiliation":[{"name":"CPCV, ENS, PSL, CNRS Sorbonne Universit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9036-6561","authenticated-orcid":false,"given":"Ludovic","family":"Carlier","sequence":"additional","affiliation":[{"name":"CPCV, ENS, PSL, CNRS Sorbonne Universit\u00e9  Paris 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