{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:19:38Z","timestamp":1791994778766,"version":"4.4.0"},"reference-count":166,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2023MH282"],"award-info":[{"award-number":["ZR2023MH282"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Celastrol, a natural compound with potent antitumor activity, has gained considerable attention in drug research and development. Although its use is limited by high toxicity, a narrow therapeutic window, and severe side effects, studies show that celastrol can inhibit tumors through multiple targets and pathways, including by inducing apoptosis, autophagy, as well as suppressing invasion and adhesion. It also enhances antitumor effects by reshaping the immunosuppressive tumor microenvironment, regulating stromal components, and suppressing angiogenesis. This review systematically summarizes recent advances in related research and elaborates on the molecular mechanisms underlying the antitumor activity of celastrol and the key factors contributing to its toxicity. In addition, we further discuss current progress in research focused on reducing celastrol\u2019s toxicity and enhancing its efficacy, aiming to promote its safety and druggability through rational structural modification, target optimization, and advanced formulation development.<\/jats:p>","DOI":"10.3390\/biom16050620","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T10:38:14Z","timestamp":1776854294000},"page":"620","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Antitumor Potential of Celastrol: Research Progress on Antitumor Mechanisms and Strategies for Toxicity Reduction with Efficacy Enhancement"],"prefix":"10.3390","volume":"16","author":[{"given":"Qian","family":"Jiang","sequence":"first","affiliation":[{"name":"School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaojing","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Cheng","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyuan","family":"Geng","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Gu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wei","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengjia","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0879-0572","authenticated-orcid":false,"given":"Yi","family":"Bi","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e2443198","DOI":"10.1001\/jamanetworkopen.2024.43198","article-title":"Global Disparities of Cancer and Its Projected Burden in 2050","volume":"7","author":"Bizuayehu","year":"2024","journal-title":"JAMA Netw. 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