{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T02:55:07Z","timestamp":1792292107189,"version":"4.4.0"},"reference-count":137,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2023,12,23]],"date-time":"2023-12-23T00:00:00Z","timestamp":1703289600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Japan Society for the Promotion of Science and the Ministry of Education, Culture, Sports, Science and Technology","award":["18H05502, 21H02955, and 23H04926"],"award-info":[{"award-number":["18H05502, 21H02955, and 23H04926"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,4,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Recently, the development of protein degraders (protein-degrading compounds) has prominently progressed. There are two remarkable classes of protein degraders: proteolysis-targeting chimeras (PROTACs) and molecular glue degraders (MGDs). Almost 70\u00a0years have passed since thalidomide was initially developed as a sedative-hypnotic drug, which is currently recognized as one of the most well-known MGDs. During the last two decades, a myriad of PROTACs and MGDs have been developed, and the molecular mechanism of action (MOA) of thalidomide was basically elucidated, including identifying its molecular target cereblon (CRBN). CRBN forms a Cullin Ring Ligase 4 with Cul4 and DDB1, whose substrate specificity is controlled by its binding ligands. Thalidomide, lenalidomide and pomalidomide, three CRBN-binding MGDs, were clinically approved to treat several intractable diseases (including multiple myeloma). Several other MGDs and CRBN-based PROTACs (ARV-110 and AVR-471) are undergoing clinical trials. In addition, several new related technologies regarding PROTACs and MGDs have also been developed, and achievements of protein degraders impact not only therapeutic fields but also basic biological science. In this article, I introduce the history of protein degraders, from the development of thalidomide to the latest PROTACs and related technologies.<\/jats:p>","DOI":"10.1093\/jb\/mvad113","type":"journal-article","created":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T20:17:18Z","timestamp":1702412238000},"page":"507-519","source":"Crossref","is-referenced-by-count":31,"title":["Protein degraders - from thalidomide to new PROTACs"],"prefix":"10.1093","volume":"175","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9997-2664","authenticated-orcid":false,"given":"Takumi","family":"Ito","sequence":"first","affiliation":[{"name":"Tokyo Medical University Institute of Medical Science, , 6-1-1, Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,12,23]]},"reference":[{"key":"2024050904162481400_ref1","doi-asserted-by":"crossref","first-page":"6234","DOI":"10.1039\/D2CS00116K","article-title":"Discovery of CRBN as a target of thalidomide: a breakthrough for progress in the development of protein degraders","volume":"51","author":"Yamamoto","year":"2022","journal-title":"Chem. 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