{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T13:02:42Z","timestamp":1781701362227,"version":"3.54.5"},"reference-count":23,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100007301","name":"Kunming University of Science and Technology","doi-asserted-by":"publisher","award":["202202AG050008"],"award-info":[{"award-number":["202202AG050008"]}],"id":[{"id":"10.13039\/501100007301","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005273","name":"Natural Science Foundation of Yunnan Province","doi-asserted-by":"publisher","award":["202401CF070152"],"award-info":[{"award-number":["202401CF070152"]}],"id":[{"id":"10.13039\/501100005273","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32160157"],"award-info":[{"award-number":["32160157"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Biochemical Pharmacology"],"published-print":{"date-parts":[[2026,3]]},"DOI":"10.1016\/j.bcp.2025.117629","type":"journal-article","created":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T00:20:40Z","timestamp":1765412440000},"page":"117629","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Celastrol synergizes with MEK1 inhibitor nedometinib to overcome resistance in bladder cancer via dual suppression of CDK1\/CDC5L and feedback-activated Akt\/STAT3"],"prefix":"10.1016","volume":"245","author":[{"given":"Wu-Shuang","family":"Jiang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei-Xue","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue-Xuan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Song","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen-Kai","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jue","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian-Rui","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8227-0618","authenticated-orcid":false,"given":"Jun","family":"Sang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bcp.2025.117629_b0005","doi-asserted-by":"crossref","first-page":"17022","DOI":"10.1038\/nrdp.2017.22","article-title":"Bladder cancer","volume":"3","author":"Sanli","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"10.1016\/j.bcp.2025.117629_b0010","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.euf.2019.10.017","article-title":"Neoadjuvant therapies for bladder cancer in cisplatin-ineligible patients: what options do we have?","volume":"6","author":"Basu","year":"2020","journal-title":"Eur. Urol. Focus"},{"key":"10.1016\/j.bcp.2025.117629_b0015","doi-asserted-by":"crossref","DOI":"10.15252\/emmm.201910880","article-title":"Phosphorylation of TFCP2L1 by CDK1 is required for stem cell pluripotency and bladder carcinogenesis","volume":"12","author":"Heo","year":"2020","journal-title":"EMBO Mol. Med."},{"key":"10.1016\/j.bcp.2025.117629_b0020","doi-asserted-by":"crossref","first-page":"353","DOI":"10.7150\/jca.32850","article-title":"Depletion of CDC5L inhibits bladder cancer tumorigenesis","volume":"11","author":"Zhang","year":"2020","journal-title":"J. Cancer"},{"key":"10.1016\/j.bcp.2025.117629_b0025","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/s41392-023-01705-z","article-title":"Targeting the RAS\/RAF\/MAPK pathway for cancer therapy: from mechanism to clinical studies","volume":"8","author":"Bahar","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"10.1016\/j.bcp.2025.117629_b0030","article-title":"Topical MEK1\/2 inhibitor therapy reduces tumor burden and prolongs survival in a murine model of cutaneous squamous cell carcinoma","volume":"15","author":"Sarin","year":"2023","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.bcp.2025.117629_b0035","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.adk4946","article-title":"Effect of NFX-179 MEK inhibitor on cutaneous neurofibromas in persons with neurofibromatosis type 1","volume":"10","author":"Sarin","year":"2024","journal-title":"Sci. Adv."},{"key":"10.1016\/j.bcp.2025.117629_b0040","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1080\/15384047.2021.1919004","article-title":"Anti-tumor effect of trametinib in bladder cancer organoid and the underlying mechanism","volume":"22","author":"Elbadawy","year":"2021","journal-title":"Cancer Biol. Ther."},{"key":"10.1016\/j.bcp.2025.117629_b0045","doi-asserted-by":"crossref","DOI":"10.1016\/j.ctrv.2020.102137","article-title":"MEK inhibitor resistance mechanisms and recent developments in combination trials","volume":"92","author":"Kun","year":"2021","journal-title":"Cancer Treat. Rev."},{"key":"10.1016\/j.bcp.2025.117629_b0050","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1158\/1541-7786.MCR-17-0404","article-title":"Targeting CDK1 and MEK\/ERK overcomes apoptotic resistance in BRAF-mutant human colorectal cancer","volume":"16","author":"Zhang","year":"2018","journal-title":"Mol. Cancer Res."},{"key":"10.1016\/j.bcp.2025.117629_b0055","first-page":"195","article-title":"Progress in approved drugs from natural product resources","volume":"22","author":"Luo","year":"2024","journal-title":"Chin. J. Nat. Med."},{"key":"10.1016\/j.bcp.2025.117629_b0060","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2025.119560","article-title":"Targeting metabolic diseases with celastrol: a comprehensive review of anti-inflammatory mechanisms and therapeutic potential","volume":"344","author":"Wang","year":"2025","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.bcp.2025.117629_b0065","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.canlet.2021.08.030","article-title":"Celastrol in cancer therapy: recent developments, challenges and prospects","volume":"521","author":"Lim","year":"2021","journal-title":"Cancer Lett."},{"key":"10.1016\/j.bcp.2025.117629_b0070","doi-asserted-by":"crossref","DOI":"10.1016\/j.bcp.2024.116194","article-title":"Jolkinolide B synergistically potentiates the antitumor activity of GPX4 inhibitors via inhibiting TrxR1 in cisplatin-resistant bladder cancer cells","volume":"223","author":"Sang","year":"2024","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.bcp.2025.117629_b0075","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.canlet.2021.03.030","article-title":"Jolkinolide B targets thioredoxin and glutathione systems to induce ROS-mediated paraptosis and apoptosis in bladder cancer cells","volume":"509","author":"Sang","year":"2021","journal-title":"Cancer Lett."},{"key":"10.1016\/j.bcp.2025.117629_b0080","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1093\/carcin\/bgs102","article-title":"Celastrol decreases specificity proteins (Sp) and fibroblast growth factor receptor-3 (FGFR3) in bladder cancer cells","volume":"33","author":"Chadalapaka","year":"2012","journal-title":"Carcinogenesis"},{"key":"10.1016\/j.bcp.2025.117629_b0085","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/s41392-022-01231-4","article-title":"Celastrol suppresses colorectal cancer via covalent targeting peroxiredoxin 1","volume":"8","author":"Xu","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"10.1016\/j.bcp.2025.117629_b0090","doi-asserted-by":"crossref","first-page":"770","DOI":"10.3724\/abbs.2024192","article-title":"Clitoria ternatea L. flower-derived anthocyanins and flavonoids inhibit bladder cancer growth by suppressing SREBP1 pathway-mediated fatty acid synthesis","volume":"57","author":"Liu","year":"2025","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"10.1016\/j.bcp.2025.117629_b0095","doi-asserted-by":"crossref","unstructured":"J. Liu, Y.-X. Liu, Y.-S. Song, C.-K. Liu, F.-X. Yu, G. Liu, T.-R. Xu, J. Sang, Targeting GRB2-Akt-SREBP1 signaling axis by saponins from Paris polyphylla Smith var. yunnanensis (Franch.) Hand.-Mazz to overcome cisplatin resistance in bladder cancer, J. Ethnopharmacol. 354 (2026) 120502, https:\/\/doi.org\/10.1016\/j.jep.2025.120502.","DOI":"10.1016\/j.jep.2025.120502"},{"key":"10.1016\/j.bcp.2025.117629_b0100","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1038\/s41416-023-02468-8","article-title":"The cyclin-dependent kinase 1: more than a cell cycle regulator","volume":"129","author":"Massacci","year":"2023","journal-title":"Br. J. Cancer"},{"key":"10.1016\/j.bcp.2025.117629_b0105","doi-asserted-by":"crossref","first-page":"6538","DOI":"10.1038\/s41467-024-50678-2","article-title":"Rosiglitazone and trametinib exhibit potent anti-tumor activity in a mouse model of muscle invasive bladder cancer","volume":"15","author":"Plumber","year":"2024","journal-title":"Nat. Commun."},{"key":"10.1016\/j.bcp.2025.117629_b0110","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1038\/s12276-020-0384-2","article-title":"ROS in cancer therapy: the bright side of the moon","volume":"52","author":"Perillo","year":"2020","journal-title":"Exp. Mol. Med."},{"key":"10.1016\/j.bcp.2025.117629_b0115","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1002\/med.21734","article-title":"Small molecules regulating reactive oxygen species homeostasis for cancer therapy","volume":"41","author":"Zhang","year":"2021","journal-title":"Med. Res. Rev."}],"container-title":["Biochemical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006295225008949?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006295225008949?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T12:20:46Z","timestamp":1781698846000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0006295225008949"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3]]},"references-count":23,"alternative-id":["S0006295225008949"],"URL":"https:\/\/doi.org\/10.1016\/j.bcp.2025.117629","relation":{},"ISSN":["0006-2952"],"issn-type":[{"value":"0006-2952","type":"print"}],"subject":[],"published":{"date-parts":[[2026,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Celastrol synergizes with MEK1 inhibitor nedometinib to overcome resistance in bladder cancer via dual suppression of CDK1\/CDC5L and feedback-activated Akt\/STAT3","name":"articletitle","label":"Article Title"},{"value":"Biochemical Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bcp.2025.117629","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"117629"}}