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However, the ambiguity of target information poses a significant challenge in transitioning CEL from a traditional remedy to a modern pharmaceutical agent. Recently, the emerging target discovery approaches of natural products have broadened extensive avenues for uncovering comprehensive target information of CEL and promoting its drug development. Herein, diverse target discovery strategies are overviewed for the pharmacological and toxicological studies of CEL, including chemical proteomics, protein microarray, degradation\u2010based protein profiling, proteome\u2010wide label\u2010free approaches, network pharmacology, target\u2010based drug screening, multi\u2010omics analysis, and hypothesis\u2010driven target confirmation. Dozens of CEL targets have been identified, which significantly suggests that CEL functions as a multi\u2010target therapeutic agent. Further network interaction analysis and frequency analysis of collected targets reveal that PRDXs, HMGB1, HSP90, STAT3, and PKM2 may serve as key targets for CEL. Additionally, this review highlights the positive role of target discovery in facilitating CEL\u2010based combination therapy and drug delivery, which is essential for further advancing the clinical applications of CEL. Efforts in CEL target identification not only aid in unraveling the scientific underpinnings of its multiple pharmacological effects but also offer crucial insights for further drug development of CEL\u2010based drugs.<\/jats:p>","DOI":"10.1002\/exp.20240247","type":"journal-article","created":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T01:36:36Z","timestamp":1745372196000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Emerging Target Discovery Strategies Drive the Decoding of Therapeutic Power of Natural Products and Further Drug Development: A Case Study of Celastrol"],"prefix":"10.1002","volume":"5","author":[{"given":"Yanbei","family":"Tu","sequence":"first","affiliation":[{"name":"School of Pharmacy Jiangsu University  Zhenjiang Jiangsu China"},{"name":"State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences University of Macau  Taipa Macao SAR 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