{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T18:07:12Z","timestamp":1788286032995,"version":"build-2803163510"},"reference-count":38,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Regulatory Toxicology and Pharmacology"],"published-print":{"date-parts":[[2025,5]]},"DOI":"10.1016\/j.yrtph.2025.105793","type":"journal-article","created":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T16:22:12Z","timestamp":1740500532000},"page":"105793","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":8,"special_numbering":"C","title":["Nonclinical teratogenicity safety assessment of CRBN-engaging targeted protein degraders: Points to consider"],"prefix":"10.1016","volume":"158","author":[{"given":"Lise I.","family":"Loberg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1567-7918","authenticated-orcid":false,"given":"William R.","family":"Proctor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew D.","family":"Burdick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annick","family":"Cauvin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony M.","family":"DeLise","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Hemkens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas M.","family":"Hohlbaum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renee","family":"Hukkanen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alanna E.","family":"Sedgwick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Shuey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doris T.","family":"Zane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Stamp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.yrtph.2025.105793_bib1","doi-asserted-by":"crossref","first-page":"3127","DOI":"10.1038\/s41591-023-02635-7","article-title":"IRAK4 degrader in hidradenitis suppurativa and atopic dermatitis: a phase 1 trial","volume":"29","author":"Ackerman","year":"2023","journal-title":"Nat. Med."},{"key":"10.1016\/j.yrtph.2025.105793_bib2","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1086\/343821","article-title":"Duane radial ray syndrome (okihiro syndrome) maps to 20q13 and results from mutations in SALL4, a new member of the SAL family","volume":"71","author":"Al-Baradie","year":"2002","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.yrtph.2025.105793_bib3","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1038\/s41589-019-0366-7","article-title":"p63 is a cereblon substrate involved in thalidomide teratogenicity","volume":"15","author":"Asatsuma-Okumura","year":"2019","journal-title":"Nat. Chem. Biol."},{"key":"10.1016\/j.yrtph.2025.105793_bib4","doi-asserted-by":"crossref","first-page":"95","DOI":"10.3390\/ph13050095","article-title":"Molecular mechanisms of the teratogenic effects of thalidomide","volume":"13","author":"Asatsuma-Okumura","year":"2020","journal-title":"Pharmaceuticals"},{"key":"10.1016\/j.yrtph.2025.105793_bib5","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1038\/s41573-021-00371-6","article-title":"PROTAC targeted protein degraders: the past is prologue","volume":"21","author":"B\u00e9k\u00e9s","year":"2022","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.yrtph.2025.105793_bib6","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.ddtec.2019.02.002","article-title":"A critical evaluation of the approaches to targeted protein degradation for drug discovery","volume":"31","author":"Chopra","year":"2019","journal-title":"Drug Discov. Today Technol."},{"key":"10.1016\/j.yrtph.2025.105793_bib7","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1002\/bdrb.20115","article-title":"'Evaluation of the developmental toxicity of lenalidomide in rabbits'","volume":"80","author":"Christian","year":"2007","journal-title":"Birth Defects Res. Part B Dev. Reproductive Toxicol."},{"key":"10.1016\/j.yrtph.2025.105793_bib8","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.3390\/jpm11111185","article-title":"Molecular mechanisms of cereblon-interacting small molecules in multiple myeloma therapy","volume":"11","author":"Costacurta","year":"2021","journal-title":"J. Personalized Med."},{"key":"10.1016\/j.yrtph.2025.105793_bib9","doi-asserted-by":"crossref","first-page":"4082","DOI":"10.1073\/pnas.91.9.4082","article-title":"Thalidomide is an inhibitor of angiogenesis","volume":"91","author":"D'Amato","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.yrtph.2025.105793_bib10","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.38430","article-title":"Thalidomide promotes degradation of SALL4, a transcription factor implicated in Duane Radial Ray syndrome","volume":"7","author":"Donovan","year":"2018","journal-title":"Elife"},{"key":"10.1016\/j.yrtph.2025.105793_bib13","doi-asserted-by":"crossref","DOI":"10.1016\/j.mcpro.2024.100797","article-title":"Differential analysis of cereblon neosubstrates in rabbit embryos using targeted proteomics","volume":"23","author":"Federspiel","year":"2024","journal-title":"Mol. Cell. Proteomics"},{"key":"10.1016\/j.yrtph.2025.105793_bib14","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1182\/blood-2018-05-852798","article-title":"Crbn I391V is sufficient to confer in vivo sensitivity to thalidomide and its derivatives in mice","volume":"132","author":"Fink","year":"2018","journal-title":"Blood"},{"key":"10.1016\/j.yrtph.2025.105793_bib15","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/nature13527","article-title":"Structure of the DDB1\u2013CRBN E3 ubiquitin ligase in complex with thalidomide","volume":"512","author":"Fischer","year":"2014","journal-title":"Nature"},{"key":"10.1016\/j.yrtph.2025.105793_bib16","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/0041-008X(65)90095-5","article-title":"Teratogenic effects of thalidomide in rabbits, rats, hamsters, and mice","volume":"7","author":"Fratta","year":"1965","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"10.1016\/j.yrtph.2025.105793_bib17","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2020.110114","article-title":"Recent advances in the molecular mechanism of thalidomide teratogenicity","volume":"127","author":"Gao","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.yrtph.2025.105793_bib18","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s40364-020-0182-y","article-title":"Novel immunomodulatory drugs and neo-substrates","volume":"8","author":"Gao","year":"2020","journal-title":"Biomark. Res."},{"key":"10.1016\/j.yrtph.2025.105793_bib19","doi-asserted-by":"crossref","DOI":"10.1016\/j.drudis.2023.103643","article-title":"Industry perspective on the nonclinical safety assessment of heterobifunctional degraders","author":"Hemkens","year":"2023","journal-title":"Drug Discov. Today"},{"key":"10.1016\/j.yrtph.2025.105793_bib20","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.1212\/01.WNL.0000146196.01316.A2","article-title":"A mutation in a novel ATP-dependent Lon protease gene in a kindred with mild mental retardation","volume":"63","author":"Higgins","year":"2004","journal-title":"Neurology"},{"key":"10.1016\/j.yrtph.2025.105793_bib21","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1007\/s40265-017-0689-1","article-title":"Immunomodulatory drugs in multiple myeloma: mechanisms of action and clinical experience","volume":"77","author":"Holstein","year":"2017","journal-title":"Drugs"},{"key":"10.1016\/j.yrtph.2025.105793_bib22","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.reprotox.2022.10.005","article-title":"'Embryo-fetal exposure and developmental outcome of lenalidomide following oral administration to pregnant cynomolgus monkeys'","volume":"114","author":"Hui","year":"2022","journal-title":"Reprod. Toxicol."},{"key":"10.1016\/j.yrtph.2025.105793_bib23","series-title":"Detection of Reproductive and Developmental Toxicity for Human Pharmaceuticals S5(R3)","year":"2020"},{"key":"10.1016\/j.yrtph.2025.105793_bib24","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1126\/science.1177319","article-title":"Identification of a primary target of thalidomide teratogenicity","volume":"327","author":"Ito","year":"2010","journal-title":"Science"},{"key":"10.1016\/j.yrtph.2025.105793_bib25","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1007\/s00424-016-1854-1","article-title":"Cereblon in health and disease","volume":"468","author":"Kim","year":"2016","journal-title":"Pflueg. Arch. Eur. J. Physiol."},{"key":"10.1016\/j.yrtph.2025.105793_bib26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/toxsci\/kfr088","article-title":"Thalidomide: the tragedy of birth defects and the effective treatment of disease","volume":"122","author":"Kim","year":"2011","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.yrtph.2025.105793_bib27","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1002\/humu.20215","article-title":"SALL4 mutations in Okihiro syndrome (Duane\u2010radial ray syndrome), acro\u2010renal\u2010ocular syndrome, and related disorders","volume":"26","author":"Kohlhase","year":"2005","journal-title":"Hum. Mutat."},{"key":"10.1016\/j.yrtph.2025.105793_bib28","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1002\/tera.1420380303","article-title":"A short history of thalidomide embryopathy","volume":"38","author":"Lenz","year":"1988","journal-title":"Teratology"},{"key":"10.1016\/j.yrtph.2025.105793_bib29","doi-asserted-by":"crossref","first-page":"6509","DOI":"10.1038\/s41467-023-42233-2","article-title":"Expanding PROTACtable genome universe of E3 ligases","volume":"14","author":"Liu","year":"2023","journal-title":"Nat. Commun."},{"key":"10.1016\/j.yrtph.2025.105793_bib30","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1002\/bdr2.1984","article-title":"'Toward better assessments of developmental toxicity using stem cell\u2010based in vitro embryogenesis models'","volume":"114","author":"Marikawa","year":"2022","journal-title":"Birth Defects Research"},{"key":"10.1016\/j.yrtph.2025.105793_bib31","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/s41594-020-0405-9","article-title":"Crystal structure of the SALL4\u2013pomalidomide\u2013cereblon\u2013DDB1 complex","volume":"27","author":"Matyskiela","year":"2020","journal-title":"Nat. Struct. Mol. Biol."},{"key":"10.1016\/j.yrtph.2025.105793_bib32","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1038\/s41589-018-0129-x","article-title":"SALL4 mediates teratogenicity as a thalidomide-dependent cereblon substrate","volume":"14","author":"Matyskiela","year":"2018","journal-title":"Nat. Chem. Biol."},{"key":"10.1016\/j.yrtph.2025.105793_bib33","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2023.115444","article-title":"Current advances of small molecule E3 ligands for proteolysis-targeting chimeras design","volume":"256","author":"Mi","year":"2023","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.yrtph.2025.105793_bib34","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.pharmthera.2017.02.027","article-title":"Targeted protein degradation by PROTACs","volume":"174","author":"Neklesa","year":"2017","journal-title":"Pharmacol. Therapeut."},{"key":"10.1016\/j.yrtph.2025.105793_bib35","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1038\/8466","article-title":"Free radical-mediated oxidative DNA damage in the mechanism of thalidomide teratogenicity","volume":"5","author":"Parman","year":"1999","journal-title":"Nat. Med."},{"key":"10.1016\/j.yrtph.2025.105793_bib36","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1038\/s41573-019-0047-y","article-title":"Targeted protein degradation: expanding the toolbox","volume":"18","author":"Schapira","year":"2019","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.yrtph.2025.105793_bib37","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/S0022-3565(25)27910-1","article-title":"A comparison of the teratogenic activity of thalidomide in rabbits and rats","volume":"160","author":"Schumacher","year":"1968","journal-title":"J. Pharmacol. Exp. Therapeut."},{"key":"10.1016\/j.yrtph.2025.105793_bib38","first-page":"140","article-title":"\u2018Thalidomide-induced teratogenesis: history and mechanisms\u2019, birth defects research","volume":"105","author":"Vargesson","year":"2015","journal-title":"Part. Char."},{"key":"10.1016\/j.yrtph.2025.105793_bib39","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1039\/c8ib00082d","article-title":"Teratogen screening with human pluripotent stem cells","volume":"10","author":"Worley","year":"2018","journal-title":"Integr. Biol."},{"key":"10.1016\/j.yrtph.2025.105793_bib40","doi-asserted-by":"crossref","DOI":"10.15252\/embj.2020105375","article-title":"Thalidomide and its metabolite 5\u2010hydroxythalidomide induce teratogenicity via the cereblon neosubstrate PLZF","volume":"40","author":"Yamanaka","year":"2021","journal-title":"EMBO J."}],"container-title":["Regulatory Toxicology and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0273230025000236?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0273230025000236?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T11:54:53Z","timestamp":1741694093000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0273230025000236"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5]]},"references-count":38,"alternative-id":["S0273230025000236"],"URL":"https:\/\/doi.org\/10.1016\/j.yrtph.2025.105793","relation":{},"ISSN":["0273-2300"],"issn-type":[{"value":"0273-2300","type":"print"}],"subject":[],"published":{"date-parts":[[2025,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Nonclinical teratogenicity safety assessment of CRBN-engaging targeted protein degraders: Points to consider","name":"articletitle","label":"Article Title"},{"value":"Regulatory Toxicology and Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.yrtph.2025.105793","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"simple-article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"105793"}}