{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T15:03:22Z","timestamp":1780499002276,"version":"3.54.1"},"reference-count":169,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T00:00:00Z","timestamp":1762473600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Clinical Research Excellence Program for Research-Oriented Wards","award":["BRWEP2024W034010103"],"award-info":[{"award-number":["BRWEP2024W034010103"]}]},{"name":"National Key Research and Development Program of China","award":["2024YFA0918504"],"award-info":[{"award-number":["2024YFA0918504"]}]},{"DOI":"10.13039\/501100004826","name":"Beijing Municipal Natural Science Foundation","doi-asserted-by":"publisher","award":["L232016, 7232123"],"award-info":[{"award-number":["L232016, 7232123"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Science and Technology Planning Project of Tibet Autonomous Region","award":["XZ202501JD0021"],"award-info":[{"award-number":["XZ202501JD0021"]}]},{"name":"Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences","award":["2022-I2M-1-003"],"award-info":[{"award-number":["2022-I2M-1-003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Thalidomide, once withdrawn due to teratogenicity, has re-emerged as a repurposed agent to treat a broad spectrum of diseases because of its anti-inflammatory, immunomodulatory, and anti-angiogenic properties. Over the past two decades, thalidomide has also been increasingly used in digestive diseases, including gastrointestinal and hepatobiliary\u2013pancreatic disorders. Despite these expanding indications, its broader clinical use remains restricted by safety concerns and the absence of standardized, evidence-based guidance. In particular, practical strategies for optimizing efficacy while minimizing toxicity have not been systematically summarized. This review aims to provide an updated, integrated, and clinically oriented overview of thalidomide in digestive diseases, summarizing the expanded applications from immune-mediated to non-immune-related conditions, highlighting real-world applications, therapeutic strategies, and approaches to risk mitigation. Furthermore, we discuss structural analogs and novel delivery systems that may enhance safety and efficacy, paving the way for thalidomide\u2019s rational and safe use as a modern \u201cphoenix drug\u201d.<\/jats:p>","DOI":"10.3390\/ph18111689","type":"journal-article","created":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T14:55:15Z","timestamp":1762527315000},"page":"1689","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Renaissance of Phoenix Drug Thalidomide\u2014New Insights into Practical Clinical Application and Optimization Strategies for Managing Adverse Effects in Digestive Diseases"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5153-0528","authenticated-orcid":false,"given":"Xiaxiao","family":"Yan","sequence":"first","affiliation":[{"name":"Department of Emergency, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"},{"name":"Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7579-0592","authenticated-orcid":false,"given":"Ziqi","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9222-7327","authenticated-orcid":false,"given":"Chengzhen","family":"Lyu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rou","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rutong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongwei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wangyang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2265-7092","authenticated-orcid":false,"given":"Kun","family":"He","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9430-9874","authenticated-orcid":false,"given":"Dong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"},{"name":"Department of Gastroenterology, People\u2019s Hospital of Xizang Autonomous Region, Lhasa 850000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,7]]},"reference":[{"key":"ref_1","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":"Loughnan","year":"1994","journal-title":"Proc. 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