{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T03:39:55Z","timestamp":1768707595768,"version":"3.49.0"},"reference-count":31,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"am","delay-in-days":239,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/100001395","name":"Wisconsin Alumni Research Foundation","doi-asserted-by":"publisher","award":["UW2020"],"award-info":[{"award-number":["UW2020"]}],"id":[{"id":"10.13039\/100001395","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005440","name":"National Institutes of Health Center for Scientific Review","doi-asserted-by":"publisher","award":["T32GM141013"],"award-info":[{"award-number":["T32GM141013"]}],"id":[{"id":"10.13039\/100005440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005440","name":"National Institutes of Health Center for Scientific Review","doi-asserted-by":"publisher","award":["P30 CA014520"],"award-info":[{"award-number":["P30 CA014520"]}],"id":[{"id":"10.13039\/100005440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005440","name":"National Institutes of Health Center for Scientific Review","doi-asserted-by":"publisher","award":["RF1AG064909"],"award-info":[{"award-number":["RF1AG064909"]}],"id":[{"id":"10.13039\/100005440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005440","name":"National Institutes of Health Center for Scientific Review","doi-asserted-by":"publisher","award":["R35GM148266"],"award-info":[{"award-number":["R35GM148266"]}],"id":[{"id":"10.13039\/100005440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012787","name":"Office of the Vice Chancellor for Research and Graduate Education, University of Wisconsin-Madison","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012787","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007923","name":"University of Wisconsin Carbone Cancer Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007923","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Medicinal Chemistry"],"published-print":{"date-parts":[[2025,10]]},"DOI":"10.1016\/j.ejmech.2025.117793","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T03:40:52Z","timestamp":1747798852000},"page":"117793","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":5,"special_numbering":"C","title":["Characterization of a dual degrader of MDM2 and GSPT1"],"prefix":"10.1016","volume":"295","author":[{"given":"Ira","family":"Tandon","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paulina N.","family":"Esguerra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunrong","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huan","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ka","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongrui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junmin","family":"Peng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0039-3196","authenticated-orcid":false,"given":"Weiping","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejmech.2025.117793_bib1","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/358015a0","article-title":"P53, guardian of the genome","volume":"358","author":"Lane","year":"1992","journal-title":"Nature"},{"key":"10.1016\/j.ejmech.2025.117793_bib2","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1038\/nrc991","article-title":"Inhibiting the P53\u2013MDM2 interaction: an important target for cancer therapy","volume":"3","author":"Chene","year":"2003","journal-title":"Nat. Rev. Cancer"},{"issue":"9","key":"10.1016\/j.ejmech.2025.117793_bib3","doi-asserted-by":"crossref","first-page":"2617","DOI":"10.1182\/blood.V82.9.2617.2617","article-title":"The human MDM-2 oncogene is overexpressed in leukemias","volume":"82","author":"Bueso-Ramos","year":"1993","journal-title":"Blood"},{"issue":"10","key":"10.1016\/j.ejmech.2025.117793_bib4","doi-asserted-by":"crossref","DOI":"10.1016\/j.jsps.2023.101790","article-title":"Advancements in MDM2 inhibition: clinical and pre-clinical investigations of combination therapeutic regimens","volume":"31","author":"Alaseem","year":"2023","journal-title":"Saudi Pharm. J."},{"issue":"3","key":"10.1016\/j.ejmech.2025.117793_bib5","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1021\/jm501092z","article-title":"Small-molecule inhibitors of the MDM2-P53 protein-protein interaction (MDM2 inhibitors) in clinical trials for cancer treatment","volume":"58","author":"Zhao","year":"2014","journal-title":"J. Med. Chem."},{"issue":"1","key":"10.1016\/j.ejmech.2025.117793_bib6","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.cell.2019.11.031","article-title":"Proteolysis-targeting chimeras as therapeutics and tools for biological discovery","volume":"181","author":"Burslem","year":"2020","journal-title":"Cell"},{"key":"10.1016\/j.ejmech.2025.117793_bib7","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/j.ejmech.2019.05.046","article-title":"Development of selective small molecule MDM2 degraders based on nutlin","volume":"176","author":"Wang","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.117793_bib8","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1021\/acs.jmedchem.8b00909","article-title":"Discovery of MD-224 as a First-in-Class, highly potent, and efficacious proteolysis targeting chimera murine double minute 2 degrader capable of achieving complete and durable tumor regression","volume":"62","author":"Li","year":"2019","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.117793_bib9","article-title":"An MDM2 degrader for treatment of acute leukemias","author":"Marcellino","year":"2022","journal-title":"Leukemia"},{"issue":"5","key":"10.1016\/j.ejmech.2025.117793_bib10","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1158\/2159-8290.CD-22-1131","article-title":"Targeted MDM2 degradation reveals a new vulnerability for P53-Inactivated triple-negative breast cancer","volume":"13","author":"Adams","year":"2023","journal-title":"Cancer Discov."},{"issue":"4","key":"10.1016\/j.ejmech.2025.117793_bib11","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1158\/1535-7163.MCT-24-0306","article-title":"KT-253, a novel MDM2 degrader and P53 stabilizer, has superior potency and efficacy than MDM2 small-molecule inhibitors","volume":"24","author":"Chutake","year":"2025","journal-title":"Mol. Cancer Therapeut."},{"key":"10.1016\/j.ejmech.2025.117793_bib12","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1038\/s41557-023-01379-8","article-title":"Proteolysis-targeting chimeras with reduced off-targets","volume":"16","author":"Nguyen","year":"2024","journal-title":"Nat. Chem."},{"key":"10.1016\/j.ejmech.2025.117793_bib13","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1038\/nature18611","article-title":"A novel cereblon modulator recruits GSPT1 to the CRL4CRBN ubiquitin ligase","volume":"535","author":"Matyskiela","year":"2016","journal-title":"Nature"},{"issue":"5","key":"10.1016\/j.ejmech.2025.117793_bib14","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1182\/blood.2020008676","article-title":"CC-90009, a novel cereblon E3 ligase modulator, targets acute myeloid leukemia blasts and leukemia stem cells","volume":"137","author":"Surka","year":"2021","journal-title":"Blood"},{"issue":"3","key":"10.1016\/j.ejmech.2025.117793_bib15","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1039\/D2MD00347C","article-title":"Structural rationalization of GSPT1 and IKZF1 degradation by thalidomide molecular glue derivatives","volume":"14","author":"Nowak","year":"2023","journal-title":"RSC Med. Chem."},{"key":"10.1016\/j.ejmech.2025.117793_bib16","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-023-40385-9","article-title":"Lenalidomide derivatives and proteolysis-targeting chimeras for controlling neosubstrate degradation","volume":"14","author":"Yamanaka","year":"2023","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ejmech.2025.117793_bib17","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2023.115580","article-title":"Discovery of new lenalidomide derivatives as potent and selective GSPT1 degraders","volume":"258","author":"Wei","year":"2023","journal-title":"Eur. J. Med. Chem."},{"issue":"11","key":"10.1016\/j.ejmech.2025.117793_bib18","doi-asserted-by":"crossref","first-page":"7296","DOI":"10.1021\/acs.jmedchem.0c01313","article-title":"Identification of potent, selective, and orally bioavailable small-molecule GSPT1\/2 degraders from a focused library of cereblon modulators","volume":"64","author":"Nishiguchi","year":"2021","journal-title":"J. Med. Chem."},{"issue":"21","key":"10.1016\/j.ejmech.2025.117793_bib19","doi-asserted-by":"crossref","first-page":"9471","DOI":"10.1021\/acs.jmedchem.9b00846","article-title":"Simple structural modifications converting a bona fide MDM2 PROTAC degrader into a molecular glue molecule: a cautionary tale in the design of PROTAC degraders","volume":"62","author":"Yang","year":"2019","journal-title":"J. Med. Chem."},{"issue":"4","key":"10.1016\/j.ejmech.2025.117793_bib20","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1021\/acs.jmedchem.0c01489","article-title":"CC-90009: a cereblon E3 ligase modulating drug that promotes selective degradation of GSPT1 for the treatment of acute myeloid leukemia","volume":"64","author":"Hansen","year":"2021","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.117793_bib21","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2021.105505","article-title":"A novel cereblon E3 ligase modulator with antitumor activity in gastrointestinal cancer","volume":"119","author":"Lier","year":"2022","journal-title":"Bioorg. Chem."},{"key":"10.1016\/j.ejmech.2025.117793_bib22","unstructured":"ATCC. Leukemia P53 Hotspot Mutation Cell Panel."},{"key":"10.1016\/j.ejmech.2025.117793_bib23","unstructured":"CKB CORE. https:\/\/ckb.genomenon.com\/."},{"issue":"16","key":"10.1016\/j.ejmech.2025.117793_bib24","doi-asserted-by":"crossref","first-page":"4088","DOI":"10.3390\/cancers13164088","article-title":"The function of the mutant P53-R175H in cancer","volume":"13","author":"Chiang","year":"2021","journal-title":"Cancers (Basel)"},{"issue":"16","key":"10.1016\/j.ejmech.2025.117793_bib25","doi-asserted-by":"crossref","first-page":"5619","DOI":"10.1128\/MCB.00035-07","article-title":"Human eukaryotic release factor 3a depletion causes cell cycle arrest at G1 phase through inhibition of the MTOR pathway","volume":"27","author":"Chauvin","year":"2007","journal-title":"Mol. Cell Biol."},{"issue":"7","key":"10.1016\/j.ejmech.2025.117793_bib26","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1021\/acschembio.4c00152","article-title":"Confounding factors in targeted degradation of short-lived proteins","volume":"19","author":"Vetma","year":"2024","journal-title":"ACS Chem. Biol."},{"key":"10.1016\/j.ejmech.2025.117793_bib27","article-title":"Deep proteome profiling by isobaric labeling, extensive liquid chromatography, mass spectrometry, and software-assisted quantification","volume":"129","author":"High","year":"2017","journal-title":"J. Vis. Exp."},{"issue":"12","key":"10.1016\/j.ejmech.2025.117793_bib28","doi-asserted-by":"crossref","first-page":"3663","DOI":"10.1074\/mcp.O114.039586","article-title":"A tag-based database search tool for peptide identification with high sensitivity and accuracy","volume":"13","author":"Wang","year":"2014","journal-title":"Mol. Cell. Proteomics"},{"issue":"1","key":"10.1016\/j.ejmech.2025.117793_bib29","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1021\/pr025556v","article-title":"Evaluation of multidimensional chromatography coupled with tandem mass spectrometry (LC\/LC-MS\/MS) for large-scale protein analysis: the yeast proteome","volume":"2","author":"Peng","year":"2003","journal-title":"J. Proteome Res."},{"issue":"5","key":"10.1016\/j.ejmech.2025.117793_bib30","doi-asserted-by":"crossref","first-page":"2956","DOI":"10.1021\/acs.analchem.6b04415","article-title":"Extensive peptide fractionation and Y1 ion-based interference detection method for enabling accurate quantification by isobaric labeling and mass spectrometry","volume":"89","author":"Niu","year":"2017","journal-title":"Anal. Chem."},{"issue":"6","key":"10.1016\/j.ejmech.2025.117793_bib31","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1016\/j.neuron.2019.12.015","article-title":"Deep multilayer brain proteomics identifies molecular networks in alzheimer's disease progression","volume":"105","author":"Bai","year":"2020","journal-title":"Neuron"}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523425005586?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523425005586?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T14:09:28Z","timestamp":1762265368000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523425005586"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10]]},"references-count":31,"alternative-id":["S0223523425005586"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2025.117793","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2025,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Characterization of a dual degrader of MDM2 and GSPT1","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2025.117793","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier Masson SAS. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"117793"}}