{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T15:28:31Z","timestamp":1793978911547,"version":"4.8.0"},"reference-count":33,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82404436"],"award-info":[{"award-number":["82404436"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004772","name":"Natural Science Foundation of Ningxia Province","doi-asserted-by":"publisher","award":["2024AAC03260"],"award-info":[{"award-number":["2024AAC03260"]}],"id":[{"id":"10.13039\/501100004772","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004772","name":"Natural Science Foundation of Ningxia Province","doi-asserted-by":"publisher","award":["2024AAC03261"],"award-info":[{"award-number":["2024AAC03261"]}],"id":[{"id":"10.13039\/501100004772","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004772","name":"Natural Science Foundation of Ningxia Province","doi-asserted-by":"publisher","award":["2025AAC020084"],"award-info":[{"award-number":["2025AAC020084"]}],"id":[{"id":"10.13039\/501100004772","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004772","name":"Natural Science Foundation of Ningxia Province","doi-asserted-by":"publisher","award":["2026AAC031217"],"award-info":[{"award-number":["2026AAC031217"]}],"id":[{"id":"10.13039\/501100004772","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004772","name":"Natural Science Foundation of Ningxia Province","doi-asserted-by":"publisher","award":["2021AAC03525"],"award-info":[{"award-number":["2021AAC03525"]}],"id":[{"id":"10.13039\/501100004772","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004772","name":"Natural Science Foundation of Ningxia Province","doi-asserted-by":"publisher","award":["2025BEH04074"],"award-info":[{"award-number":["2025BEH04074"]}],"id":[{"id":"10.13039\/501100004772","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Medicinal Chemistry"],"published-print":{"date-parts":[[2026,12]]},"DOI":"10.1016\/j.ejmech.2026.119228","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T23:25:20Z","timestamp":1786749920000},"page":"119228","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Drug repurposing-guided discovery of novel methyl quinoline-6-carboxylate RIPK3 inhibitors through structural optimization of Gefitinib"],"prefix":"10.1016","volume":"319","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9430-6152","authenticated-orcid":false,"given":"Ying","family":"Shi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guojing","family":"Tao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruixia","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"WenJun","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanran","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejmech.2026.119228_bib1","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/s41418-017-0012-4","article-title":"Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018","volume":"25","author":"Galluzzi","year":"2018","journal-title":"Cell Death Differ."},{"key":"10.1016\/j.ejmech.2026.119228_bib2","first-page":"771","article-title":"RIP1\/RIP3-regulated necroptosis as a target for multifaceted disease therapy","volume":"44","author":"Liu","year":"2019","journal-title":"Int. J. Mol. Med."},{"key":"10.1016\/j.ejmech.2026.119228_bib3","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/ncb2883","article-title":"Plasma membrane translocation of trimerized MLKL protein is required for TNF-induced necroptosis","volume":"16","author":"Cai","year":"2014","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.ejmech.2026.119228_bib4","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1093\/cvr\/cvu146","article-title":"A kinase promoting necroptotic cell death, mediates adverse remodelling after myocardial infarction","volume":"103","author":"Luedde","year":"2014","journal-title":"Cardiovasc. Res."},{"key":"10.1016\/j.ejmech.2026.119228_bib5","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1038\/s41418-021-00872-2","article-title":"The circRNA CNEACR regulates necroptosis of cardiomyocytes through Foxa2 suppression","volume":"29","author":"Gao","year":"2022","journal-title":"Cell Death Differ."},{"key":"10.1016\/j.ejmech.2026.119228_bib6","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.yjmcc.2022.05.006","article-title":"Necroptosis in heart disease: molecular mechanisms and therapeutic implications","volume":"169","author":"Guo","year":"2022","journal-title":"J. Mol. Cell. Cardiol."},{"key":"10.1016\/j.ejmech.2026.119228_bib7","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1146\/annurev-pathol-052016-100247","article-title":"Necroptosis: mechanisms and relevance to disease","volume":"12","author":"Galluzzi","year":"2017","journal-title":"Annu. Rev. Pathol."},{"key":"10.1016\/j.ejmech.2026.119228_bib8","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1016\/j.immuni.2011.09.020","article-title":"RIP kinase-dependent necrosis drives lethal systemic inflammatory response syndrome","volume":"35","author":"Duprez","year":"2011","journal-title":"Immunity"},{"key":"10.1016\/j.ejmech.2026.119228_bib9","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1165\/rcmb.2020-0312OC","article-title":"RIPK3 activates MLKL-mediated necroptosis and inflammasome signaling during streptococcus infection","volume":"64","author":"Huang","year":"2021","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"10.1016\/j.ejmech.2026.119228_bib10","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1165\/rcmb.2018-0219OC","article-title":"TREM-1 attenuates RIPK3-mediated necroptosis in hyperoxia-induced lung injury in neonatal mice","volume":"60","author":"Syed","year":"2019","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"10.1016\/j.ejmech.2026.119228_bib11","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.nefro.2022.12.009","article-title":"RIPK3 and kidney disease","volume":"44","author":"Guerrero-Mauvecin","year":"2024","journal-title":"Nefrologia"},{"key":"10.1016\/j.ejmech.2026.119228_bib12","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1681\/ASN.2021030383","article-title":"Bone marrow-derived RIPK3 mediates kidney inflammation in acute kidney injury","volume":"33","author":"Martin-Sanchez","year":"2022","journal-title":"J. Am. Soc. Nephrol."},{"key":"10.1016\/j.ejmech.2026.119228_bib13","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.tips.2016.12.005","article-title":"Complex pathologic roles of RIPK1 and RIPK3: moving beyond necroptosis","volume":"38","author":"Wegner","year":"2017","journal-title":"Trends Pharmacol. Sci."},{"key":"10.1016\/j.ejmech.2026.119228_bib14","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/s41583-018-0093-1","article-title":"Necroptosis and RIPK1-mediated neuroinflammation in CNS diseases","volume":"20","author":"Yuan","year":"2019","journal-title":"Nat. Rev. Neurosci."},{"key":"10.1016\/j.ejmech.2026.119228_bib15","doi-asserted-by":"crossref","DOI":"10.3390\/ijms232112714","article-title":"Necroptosis: a pathogenic negotiator in human diseases","volume":"23","author":"Chaouhan","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.ejmech.2026.119228_bib16","doi-asserted-by":"crossref","first-page":"658","DOI":"10.7150\/ijbs.77994","article-title":"Targeting necroptosis: a novel therapeutic option for retinal degenerative diseases","volume":"19","author":"Zhang","year":"2023","journal-title":"Int. J. Biol. Sci."},{"key":"10.1016\/j.ejmech.2026.119228_bib17","doi-asserted-by":"crossref","first-page":"21695","DOI":"10.1073\/pnas.1009179107","article-title":"Receptor interacting protein kinases mediate retinal detachment-induced photoreceptor necrosis and compensate for inhibition of apoptosis","volume":"107","author":"Trichonas","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ejmech.2026.119228_bib18","doi-asserted-by":"crossref","DOI":"10.1038\/cddis.2015.385","article-title":"Necrotic cone photoreceptor cell death in retinitis pigmentosa","volume":"6","author":"Murakami","year":"2015","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.ejmech.2026.119228_bib19","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1186\/s12943-019-1029-8","article-title":"The role of necroptosis in cancer biology and therapy","volume":"18","author":"Gong","year":"2019","journal-title":"Mol. Cancer"},{"key":"10.1016\/j.ejmech.2026.119228_bib20","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1038\/s41422-018-0058-y","article-title":"Necroptosis of tumor cells leads to tumor necrosis and promotes tumor metastasis","volume":"28","author":"Jiao","year":"2018","journal-title":"Cell Res."},{"key":"10.1016\/j.ejmech.2026.119228_bib21","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.2005756","article-title":"BRAF and AXL oncogenes drive RIPK3 expression loss in cancer","volume":"16","author":"Najafov","year":"2018","journal-title":"PLoS Biol."},{"key":"10.1016\/j.ejmech.2026.119228_bib22","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1186\/s13045-020-00946-7","article-title":"Ferroptosis, necroptosis, and pyroptosis in anticancer immunity","volume":"13","author":"Tang","year":"2020","journal-title":"J. Hematol. Oncol."},{"key":"10.1016\/j.ejmech.2026.119228_bib23","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1111\/imr.12583","article-title":"Necroptotic cell death in anti-cancer therapy","volume":"280","author":"Krysko","year":"2017","journal-title":"Immunol. Rev."},{"key":"10.1016\/j.ejmech.2026.119228_bib24","doi-asserted-by":"crossref","first-page":"31268","DOI":"10.1074\/jbc.M113.462341","article-title":"Toll-like receptor 3-mediated necrosis via TRIF, RIP3, and MLKL","volume":"288","author":"Kaiser","year":"2013","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ejmech.2026.119228_bib25","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1186\/s12967-018-1606-4","article-title":"RIP3 dependent NLRP3 inflammasome activation is implicated in acute lung injury in mice","volume":"16","author":"Chen","year":"2018","journal-title":"J. Transl. Med."},{"key":"10.1016\/j.ejmech.2026.119228_bib26","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/s41419-023-05660-z","article-title":"RIP3-mediated microglial necroptosis promotes neuroinflammation and neurodegeneration in the early stages of diabetic retinopathy","volume":"14","author":"Huang","year":"2023","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.ejmech.2026.119228_bib27","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1038\/s41586-020-2127-x","article-title":"Gut stem cell necroptosis by genome instability triggers bowel inflammation","volume":"580","author":"Wang","year":"2020","journal-title":"Nature"},{"key":"10.1016\/j.ejmech.2026.119228_bib28","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/j.molcel.2014.10.021","article-title":"RIP3 induces apoptosis independent of pronecrotic kinase activity","volume":"56","author":"Mandal","year":"2014","journal-title":"Mol. Cell"},{"key":"10.1016\/j.ejmech.2026.119228_bib29","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1126\/science.1249361","article-title":"Activity of protein kinase RIPK3 determines whether cells die by necroptosis or apoptosis","volume":"343","author":"Newton","year":"2014","journal-title":"Science"},{"key":"10.1016\/j.ejmech.2026.119228_bib30","doi-asserted-by":"crossref","first-page":"4288","DOI":"10.1038\/s41467-025-59432-8","article-title":"Structure-based design of potent and selective inhibitors targeting RIPK3 for eliminating on-target toxicity in vitro","volume":"16","author":"Su","year":"2025","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ejmech.2026.119228_bib31","doi-asserted-by":"crossref","DOI":"10.1038\/cddis.2014.241","article-title":"The B-Raf(V600E) inhibitor dabrafenib selectively inhibits RIP3 and alleviates acetaminophen-induced liver injury","volume":"5","author":"Li","year":"2014","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.ejmech.2026.119228_bib32","doi-asserted-by":"crossref","DOI":"10.1038\/cddis.2017.298","article-title":"Sorafenib tosylate inhibits directly necrosome complex formation and protects in mouse models of inflammation and tissue injury","volume":"8","author":"Martens","year":"2017","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.ejmech.2026.119228_bib33","doi-asserted-by":"crossref","first-page":"6665","DOI":"10.1021\/acs.jmedchem.9b00611","volume":"62","author":"Zhang","year":"2019","journal-title":"J. Med. Chem."}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523426006732?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523426006732?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T15:06:22Z","timestamp":1793977582000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523426006732"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,12]]},"references-count":33,"alternative-id":["S0223523426006732"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2026.119228","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2026,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Drug repurposing-guided discovery of novel methyl quinoline-6-carboxylate RIPK3 inhibitors through structural optimization of Gefitinib","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2026.119228","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier Masson SAS. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"119228"}}