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Volume 18
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10.3390/ph18111689
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Review

Renaissance of Phoenix Drug Thalidomide—New Insights into Practical Clinical Application and Optimization Strategies for Managing Adverse Effects in Digestive Diseases

by
Xiaxiao Yan
1,2,†,
Ziqi Guo
2,†,
Chengzhen Lyu
2,
Rou Tang
3,
Rutong Li
2,
Hongwei Wang
2,
Kai Song
2,
Wangyang Chen
2,
Kun He
2,* and
Dong Wu
2,4,*
1
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
2
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
3
Department of Pharmacy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
4
Department of Gastroenterology, People’s Hospital of Xizang Autonomous Region, Lhasa 850000, China
*
Authors to whom correspondence should be addressed.
†
These authors contribute equally to this work.
Pharmaceuticals 2025, 18(11), 1689; https://doi.org/10.3390/ph18111689
Submission received: 23 September 2025 / Revised: 30 October 2025 / Accepted: 4 November 2025 / Published: 7 November 2025
(This article belongs to the Section Pharmacology)
Versions Notes

Abstract

Thalidomide, once withdrawn due to teratogenicity, has re-emerged as a repurposed agent to treat a broad spectrum of diseases because of its anti-inflammatory, immunomodulatory, and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–pancreatic 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’s rational and safe use as a modern “phoenix drug”.
Keywords: thalidomide; digestive diseases; application; adverse effects; drug delivery thalidomide; digestive diseases; application; adverse effects; drug delivery

Share and Cite

MDPI and ACS Style

Yan, X.; Guo, Z.; Lyu, C.; Tang, R.; Li, R.; Wang, H.; Song, K.; Chen, W.; He, K.; Wu, D. Renaissance of Phoenix Drug Thalidomide—New Insights into Practical Clinical Application and Optimization Strategies for Managing Adverse Effects in Digestive Diseases. Pharmaceuticals 2025, 18, 1689. https://doi.org/10.3390/ph18111689

AMA Style

Yan X, Guo Z, Lyu C, Tang R, Li R, Wang H, Song K, Chen W, He K, Wu D. Renaissance of Phoenix Drug Thalidomide—New Insights into Practical Clinical Application and Optimization Strategies for Managing Adverse Effects in Digestive Diseases. Pharmaceuticals. 2025; 18(11):1689. https://doi.org/10.3390/ph18111689

Chicago/Turabian Style

Yan, Xiaxiao, Ziqi Guo, Chengzhen Lyu, Rou Tang, Rutong Li, Hongwei Wang, Kai Song, Wangyang Chen, Kun He, and Dong Wu. 2025. "Renaissance of Phoenix Drug Thalidomide—New Insights into Practical Clinical Application and Optimization Strategies for Managing Adverse Effects in Digestive Diseases" Pharmaceuticals 18, no. 11: 1689. https://doi.org/10.3390/ph18111689

APA Style

Yan, X., Guo, Z., Lyu, C., Tang, R., Li, R., Wang, H., Song, K., Chen, W., He, K., & Wu, D. (2025). Renaissance of Phoenix Drug Thalidomide—New Insights into Practical Clinical Application and Optimization Strategies for Managing Adverse Effects in Digestive Diseases. Pharmaceuticals, 18(11), 1689. https://doi.org/10.3390/ph18111689

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