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Necroptosis and ferroptosis are two distinct types of regulated cell death that can trigger inflammation and are involved in organ injury. The inhibition of necroptosis and ferroptosis is proposed to be beneficial for treating multiple pathological conditions. To find out necroptosis and ferroptosis inhibitors, we used a small-molecule compound library for screening and identified a clinically advanced compound, Dovitinib (Dov), as a potent dual inhibitor of necroptosis and ferroptosis. Dov inhibited tumor necrosis factor (TNF)-induced necroptosis by regulating receptor-interacting protein kinase 1 (RIPK1) and alleviated TNF-mediated systemic inflammatory response syndrome. Additionally, Dov inhibited ferroptosis by regulating the NRF2\/HMOX1 axis and lipid peroxidation and protected against concanavalin A-induced acute liver injury. Thus, our work revealed that Dov is a dual inhibitor of necroptosis and ferroptosis and provides a potential therapeutic drug or combination approach for treating necroptosis- and ferroptosis-related diseases.<\/jats:p>","DOI":"10.1021\/acschembio.5c00327","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T02:42:31Z","timestamp":1755830551000},"page":"2191-2203","source":"Crossref","is-referenced-by-count":5,"title":["Dovitinib Ameliorates\nInflammation-Related Diseases\nby Inhibiting Necroptosis and Ferroptosis"],"prefix":"10.1021","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-8343-851X","authenticated-orcid":true,"given":"Yingying","family":"Lin","sequence":"first","affiliation":[{"name":"Fujian Medical University , , ,","place":["Fuzhou, China, 350004"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianting","family":"Feng","sequence":"additional","affiliation":[{"name":"Fujian Medical University , , ,","place":["Fuzhou, China, 350004"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyuan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Fujian Medical University , , ,","place":["Fuzhou, China, 350004"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Libo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Fujian Medical University , , ,","place":["Fuzhou, China, 350004"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[{"name":"Fujian Medical University , , ,","place":["Fuzhou, China, 350004"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Fujian Medical University , , ,","place":["Fuzhou, China, 350004"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuibing","family":"Lin","sequence":"additional","affiliation":[{"name":"Fujian Medical University , , ,","place":["Fuzhou, China, 350004"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junxiong","family":"Lin","sequence":"additional","affiliation":[{"name":"Fujian Medical University , , ,","place":["Fuzhou, China, 350004"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaofa","family":"Lin","sequence":"additional","affiliation":[{"name":"Fujian Medical University , , ,","place":["Fuzhou, China, 350004"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyi","family":"Li","sequence":"additional","affiliation":[{"name":"Fujian Medical University , , ,","place":["Fuzhou, China, 350004"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanqin","family":"Wu","sequence":"additional","affiliation":[{"name":"Fujian Medical University , , ,","place":["Fuzhou, China, 350004"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisheng","family":"Li","sequence":"additional","affiliation":[{"name":"Fujian Medical University , , ,","place":["Fuzhou, China, 350004"]},{"name":"Fujian Medical University , , 1 Xueyuan Road , Minhou, ,","place":["Fuzhou, China, 350004"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2025,8,21]]},"reference":[{"issue":"2","key":"2026093015093303300_cit1","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/j.cell.2023.11.044","article-title":"Cell\ndeath","volume":"187","author":"Newton","year":"2024","journal-title":"Cell"},{"issue":"14","key":"2026093015093303300_cit2","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2020107341","article-title":"Too much death can kill you: inhibiting\nintrinsic apoptosis to treat disease","volume":"40","author":"Li","year":"2021","journal-title":"EMBO J"},{"issue":"1","key":"2026093015093303300_cit3","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1016\/j.molcel.2023.11.040","article-title":"The biochemical pathways\nof apoptotic, necroptotic, pyroptotic, and\nferroptotic cell death","volume":"84","author":"Ai","year":"2024","journal-title":"Mol. 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