{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T22:28:54Z","timestamp":1793831334118,"version":"4.6.1"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T00:00:00Z","timestamp":1764288000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T00:00:00Z","timestamp":1764288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Death Discov."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    In the past two decades, various non-apoptotic pathways of regulated cell death have been identified; a small subset of these, including necroptosis and ferroptosis, manifests the phenotypic features of necrotic death. These two regulated necroses are being extensively studied because of their putative roles in severe acute and chronic pathologies. Moreover, as these regulated necrotic pathways are coactivated in a number of common pathologies, the development of multi-target directed ligands (that is, the use of a polypharmacological strategy) is a path-breaking avenue of research. In this study, we determined that the 7-azaindole derivative, sibiriline, inhibited both RIPK1-driven necroptosis (induced by Tumor Necrosis Factor-\u03b1) and ferroptosis (triggered by various classes of ferroptosis inducers), with EC\n                    <jats:sub>50<\/jats:sub>\n                    s against each in the \u00b5M range. We next performed a combined large-scale transcriptomic study in order to determine the molecular mechanisms of action of sibiriline. We identified the stress response protein heme oxygenase-1 (HMOX1) as the main biomarker of ferroptosis inhibition by sibiriline. We hypothesized that this compound reacts as an antioxidant to block ferroptosis; indeed, we found that sibiriline inhibits lipid peroxidation by trapping phospholipid-derived peroxyl radicals as a radical-trapping antioxidant (RTA). Taken together, these results show that sibiriline is a new dual inhibitor of necroptosis and ferroptosis cell death pathways; it works by inhibition of both RIPK1 kinase and (phospho)lipid peroxidation. We also demonstrate the in vitro efficacy of sibiriline to inhibit cell death in cell-based models of Parkinson\u2019s disease and cystic fibrosis. These findings shed light on the high therapeutic potency of RIPK1 inhibitors with RTA activity.\n                  <\/jats:p>","DOI":"10.1038\/s41420-025-02852-8","type":"journal-article","created":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T14:51:51Z","timestamp":1764341511000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Sibiriline, a novel dual inhibitor of necroptosis and ferroptosis, prevents RIPK1 kinase activity and (phospho)lipid peroxidation as a potential therapeutic strategy"],"prefix":"10.1038","volume":"11","author":[{"given":"Claire","family":"Delehouz\u00e9","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melodie","family":"Mallais","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud","family":"Comte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romain","family":"Lucas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blandine","family":"Baratte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"B\u00e9lal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axelle","family":"Autret","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Py","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u00e9my","family":"Steinschneider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucie","family":"Adoux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Saintpierre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9465-4774","authenticated-orcid":false,"given":"Franck","family":"Letourneur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Robert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Cougoule","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1998-9237","authenticated-orcid":false,"given":"Caio","family":"Bomfim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u00e9mi","family":"Plan\u00e8s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"P\u00e9ricat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeannette Chlo\u00eb","family":"Bulinski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Th\u00e9r\u00e8se","family":"Dimanche-Boitrel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9457-2218","authenticated-orcid":false,"given":"Peter","family":"Goekjian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etienne","family":"Meunier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgane","family":"Rousselot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7305-745X","authenticated-orcid":false,"given":"Derek A.","family":"Pratt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7186-7483","authenticated-orcid":false,"given":"St\u00e9phane","family":"Bach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,28]]},"reference":[{"key":"2852_CR1","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1038\/s41418-017-0012-4","volume":"25","author":"L Galluzzi","year":"2018","unstructured":"Galluzzi L, Vitale I, Aaronson SA, Abrams JM, Adam D, Agostinis P, et al. Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death Differ. 2018;25:486\u2013541.","journal-title":"Cell Death Differ"},{"key":"2852_CR2","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1038\/nchembio.83","volume":"4","author":"A Degterev","year":"2008","unstructured":"Degterev A, Hitomi J, Germscheid M, Ch\u2019en IL, Korkina O, Teng X, et al. Identification of RIP1 kinase as a specific cellular target of necrostatins. Nat Chem Biol. 2008;4:313\u201321.","journal-title":"Nat Chem Biol"},{"key":"2852_CR3","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/j.tcb.2019.12.009","volume":"30","author":"T Delanghe","year":"2020","unstructured":"Delanghe T, Dondelinger Y, Bertrand MJM. RIPK1 Kinase-dependent death: a symphony of phosphorylation events. Trends cell Biol. 2020;30:189\u2013200.","journal-title":"Trends cell Biol"},{"key":"2852_CR4","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1038\/s41573-020-0071-y","volume":"19","author":"L Mifflin","year":"2020","unstructured":"Mifflin L, Ofengeim D, Yuan J. Receptor-interacting protein kinase 1 (RIPK1) as a therapeutic target. Nat Rev Drug Discov. 2020;19:553\u201371.","journal-title":"Nat Rev Drug Discov"},{"key":"2852_CR5","doi-asserted-by":"publisher","first-page":"9714","DOI":"10.1073\/pnas.1901179116","volume":"116","author":"A Degterev","year":"2019","unstructured":"Degterev A, Ofengeim D, Yuan J. Targeting RIPK1 for the treatment of human diseases. Proc Natl Acad Sci USA. 2019;116:9714\u201322.","journal-title":"Proc Natl Acad Sci USA"},{"key":"2852_CR6","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1093\/lifemedi\/lnac003","volume":"1","author":"Y Yang","year":"2020","unstructured":"Yang Y, Li X, Zhang T, Xu D. RIP kinases and necroptosis in aging and aging-related diseases. Life Med. 2020;1:2\u201320.","journal-title":"Life Med"},{"key":"2852_CR7","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.976435","volume":"13","author":"L Chen","year":"2022","unstructured":"Chen L, Zhang X, Ou Y, Liu M, Yu D, Song Z, et al. Advances in RIPK1 kinase inhibitors. Front Pharm. 2022;13:976435.","journal-title":"Front Pharm"},{"key":"2852_CR8","doi-asserted-by":"publisher","first-page":"3050","DOI":"10.1111\/febs.14176","volume":"284","author":"F Le Cann","year":"2017","unstructured":"Le Cann F, Delehouze C, Leverrier-Penna S, Filliol A, Comte A, Delalande O, et al. Sibiriline, a new small chemical inhibitor of receptor-interacting protein kinase 1, prevents immune-dependent hepatitis. FEBS J. 2017;284:3050\u201368.","journal-title":"FEBS J"},{"key":"2852_CR9","doi-asserted-by":"publisher","first-page":"2665","DOI":"10.3390\/pharmaceutics14122665","volume":"14","author":"R Pelletier","year":"2022","unstructured":"Pelletier R, Gicquel T, Simoes Eugenio M, Ferron PJ, Morel I, Delehouze C, et al. A Transversal approach combining in silico, in vitro and in vivo models to describe the metabolism of the receptor interacting protein 1 kinase inhibitor sibiriline. Pharmaceutics. 2022;14:2665.","journal-title":"Pharmaceutics"},{"key":"2852_CR10","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1016\/j.cell.2012.03.042","volume":"149","author":"SJ Dixon","year":"2012","unstructured":"Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell. 2012;149:1060\u201372.","journal-title":"Cell"},{"key":"2852_CR11","doi-asserted-by":"publisher","first-page":"1180","DOI":"10.1038\/ncb3064","volume":"16","author":"JP Friedmann Angeli","year":"2014","unstructured":"Friedmann Angeli JP, Schneider M, Proneth B, Tyurina YY, Tyurin VA, Hammond VJ, et al. Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice. Nat Cell Biol. 2014;16:1180\u201391.","journal-title":"Nat Cell Biol"},{"key":"2852_CR12","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1021\/acscentsci.7b00028","volume":"3","author":"O Zilka","year":"2017","unstructured":"Zilka O, Shah R, Li B, Friedmann Angeli JP, Griesser M, Conrad M, et al. On the mechanism of cytoprotection by ferrostatin-1 and liproxstatin-1 and the role of lipid peroxidation in ferroptotic cell death. ACS Cent Sci. 2017;3:232\u201343.","journal-title":"ACS Cent Sci"},{"key":"2852_CR13","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1038\/s41392-020-00428-9","volume":"6","author":"H-f Yan","year":"2021","unstructured":"Yan H-f, Zou T, Tuo Q-z, Xu S, Li H, Belaidi AA, et al. Ferroptosis: mechanisms and links with diseases. Signal Transduct Target Ther. 2021;6:49.","journal-title":"Signal Transduct Target Ther"},{"key":"2852_CR14","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202300325","volume":"10","author":"Y Wang","year":"2023","unstructured":"Wang Y, Wu S, Li Q, Sun H, Wang H. Pharmacological inhibition of ferroptosis as a therapeutic target for neurodegenerative diseases and strokes. Adv Sci (Weinh). 2023;10:e2300325.","journal-title":"Adv Sci (Weinh)"},{"key":"2852_CR15","doi-asserted-by":"publisher","first-page":"2271","DOI":"10.2174\/1389557522666220218123404","volume":"22","author":"Z Shaghaghi","year":"2022","unstructured":"Shaghaghi Z, Motieian S, Alvandi M, Yazdi A, Asadzadeh B, Farzipour S, et al. Ferroptosis inhibitors as potential new therapeutic targets for cardiovascular disease. Mini Rev Med Chem. 2022;22:2271\u201386.","journal-title":"Mini Rev Med Chem"},{"key":"2852_CR16","doi-asserted-by":"publisher","first-page":"902","DOI":"10.1016\/j.tips.2023.08.012","volume":"44","author":"C Scarpellini","year":"2023","unstructured":"Scarpellini C, Klejborowska G, Lanthier C, Hassannia B, Vanden Berghe T, Augustyns K. Beyond ferrostatin-1: a comprehensive review of ferroptosis inhibitors. Trends Pharmacol Sci. 2023;44:902\u201316.","journal-title":"Trends Pharmacol Sci"},{"key":"2852_CR17","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1016\/j.tips.2017.02.005","volume":"38","author":"JPF Angeli","year":"2017","unstructured":"Angeli JPF, Shah R, Pratt DA, Conrad M. Ferroptosis Inhibition: mechanisms and Opportunities. Trends Pharmacol Sci. 2017;38:489\u201398.","journal-title":"Trends Pharmacol Sci"},{"key":"2852_CR18","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1038\/nchembio.118","volume":"4","author":"AL Hopkins","year":"2008","unstructured":"Hopkins AL. Network pharmacology: the next paradigm in drug discovery. Nat Chem Biol. 2008;4:682\u201390.","journal-title":"Nat Chem Biol"},{"key":"2852_CR19","doi-asserted-by":"publisher","first-page":"2029","DOI":"10.1038\/s41418-021-00814-y","volume":"28","author":"D Moujalled","year":"2021","unstructured":"Moujalled D, Strasser A, Liddell JR. Molecular mechanisms of cell death in neurological diseases. Cell Death Differ. 2021;28:2029\u201344.","journal-title":"Cell Death Differ"},{"key":"2852_CR20","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2020106700","volume":"40","author":"M Kist","year":"2021","unstructured":"Kist M, Vucic D. Cell death pathways: intricate connections and disease implications. EMBO J. 2021;40:e106700.","journal-title":"EMBO J"},{"key":"2852_CR21","doi-asserted-by":"publisher","first-page":"3631","DOI":"10.1007\/s00018-017-2547-4","volume":"74","author":"T Muller","year":"2017","unstructured":"Muller T, Dewitz C, Schmitz J, Schroder AS, Brasen JH, Stockwell BR, et al. Necroptosis and ferroptosis are alternative cell death pathways that operate in acute kidney failure. Cell Mol Life Sci. 2017;74:3631\u201345.","journal-title":"Cell Mol Life Sci"},{"key":"2852_CR22","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/9991001","volume":"2021","author":"Y Zhou","year":"2021","unstructured":"Zhou Y, Liao J, Mei Z, Liu X, Ge J. Insight into crosstalk between ferroptosis and necroptosis: novel therapeutics in ischemic stroke. Oxid Med Cell Longev. 2021;2021:9991001.","journal-title":"Oxid Med Cell Longev"},{"key":"2852_CR23","doi-asserted-by":"publisher","first-page":"2004","DOI":"10.1111\/j.1471-4159.2007.04884.x","volume":"103","author":"X Xu","year":"2007","unstructured":"Xu X, Chua CC, Kong J, Kostrzewa RM, Kumaraguru U, Hamdy RC, et al. Necrostatin-1 protects against glutamate-induced glutathione depletion and caspase-independent cell death in HT-22 cells. J Neurochem. 2007;103:2004\u201314.","journal-title":"J Neurochem"},{"key":"2852_CR24","doi-asserted-by":"publisher","first-page":"1347","DOI":"10.3390\/antiox10091347","volume":"10","author":"H Yuk","year":"2021","unstructured":"Yuk H, Abdullah M, Kim DH, Lee H, Lee SJ. Necrostatin-1 prevents ferroptosis in a RIPK1- and IDO-independent manner in hepatocellular carcinoma. Antioxid (Basel). 2021;10:1347.","journal-title":"Antioxid (Basel)"},{"key":"2852_CR25","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-09019-w","volume":"12","author":"C Delehouze","year":"2022","unstructured":"Delehouze C, Comte A, Leon-Icaza SA, Cougoule C, Hauteville M, Goekjian P, et al. Nigratine as dual inhibitor of necroptosis and ferroptosis regulated cell death. Sci Rep. 2022;12:5118.","journal-title":"Sci Rep"},{"key":"2852_CR26","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-24712-6","volume":"12","author":"W Tonnus","year":"2021","unstructured":"Tonnus W, Meyer C, Steinebach C, Belavgeni A, von Massenhausen A, Gonzalez NZ, et al. Dysfunction of the key ferroptosis-surveilling systems hypersensitizes mice to tubular necrosis during acute kidney injury. Nat Commun. 2021;12:4402.","journal-title":"Nat Commun"},{"key":"2852_CR27","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1038\/s41419-024-07157-9","volume":"15","author":"Y Zhao","year":"2024","unstructured":"Zhao Y, Wang Q, Zhu J, Cai J, Feng X, Song Q, et al. Identification of KW-2449 as a dual inhibitor of ferroptosis and necroptosis reveals that autophagy is a targetable pathway for necroptosis inhibitors to prevent ferroptosis. Cell death Dis. 2024;15:764.","journal-title":"Cell death Dis"},{"key":"2852_CR28","doi-asserted-by":"crossref","unstructured":"Lin Y, Feng J, Zhao M, Zhang L, Li Y, Chen X, et al. Dovitinib ameliorates inflammation-related diseases by inhibiting necroptosis and ferroptosis. ACS Chem Biol. 2025;20:2191\u2013203.","DOI":"10.1021\/acschembio.5c00327"},{"key":"2852_CR29","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-021-08559-0","volume":"21","author":"Y Hong","year":"2021","unstructured":"Hong Y, Lin M, Ou D, Huang Z, Shen P. A novel ferroptosis-related 12-gene signature predicts clinical prognosis and reveals immune relevancy in clear cell renal cell carcinoma. BMC Cancer. 2021;21:831.","journal-title":"BMC Cancer"},{"key":"2852_CR30","doi-asserted-by":"publisher","first-page":"9022","DOI":"10.1021\/cr500226n","volume":"114","author":"KU Ingold","year":"2014","unstructured":"Ingold KU, Pratt DA. Advances in radical-trapping antioxidant chemistry in the 21st century: a kinetics and mechanisms perspective. Chem Rev. 2014;114:9022\u201346.","journal-title":"Chem Rev"},{"key":"2852_CR31","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1021\/acscentsci.7b00589","volume":"4","author":"R Shah","year":"2018","unstructured":"Shah R, Shchepinov MS, Pratt DA. Resolving the Role of Lipoxygenases in the Initiation and Execution of Ferroptosis. ACS Cent Sci. 2018;4:387\u201396.","journal-title":"ACS Cent Sci"},{"key":"2852_CR32","doi-asserted-by":"publisher","first-page":"1594","DOI":"10.1016\/j.chembiol.2019.09.007","volume":"26","author":"R Shah","year":"2019","unstructured":"Shah R, Farmer LA, Zilka O, Van Kessel ATM, Pratt DA. Beyond DPPH: use of fluorescence-enabled inhibited autoxidation to predict oxidative cell death rescue. Cell Chem Biol. 2019;26:1594\u2013607.e1597.","journal-title":"Cell Chem Biol"},{"key":"2852_CR33","doi-asserted-by":"publisher","first-page":"966","DOI":"10.1021\/acs.accounts.5b00035","volume":"48","author":"L Valgimigli","year":"2015","unstructured":"Valgimigli L, Pratt DA. Maximizing the reactivity of phenolic and aminic radical-trapping antioxidants: just add nitrogen!. Acc Chem Res. 2015;48:966\u201375.","journal-title":"Acc Chem Res"},{"key":"2852_CR34","doi-asserted-by":"publisher","first-page":"2106","DOI":"10.1039\/b901838g","volume":"39","author":"M Lucarini","year":"2010","unstructured":"Lucarini M, Pedulli GF. Free radical intermediates in the inhibition of the autoxidation reaction. Chem Soc Rev. 2010;39:2106\u201319.","journal-title":"Chem Soc Rev"},{"key":"2852_CR35","doi-asserted-by":"publisher","first-page":"e20230104","DOI":"10.1084\/jem.20230104","volume":"220","author":"M Pinilla","year":"2023","unstructured":"Pinilla M, Mazars R, Verge R, Gorse L, Paradis M, Suire B, et al. EEF2-inactivating toxins engage the NLRP1 inflammasome and promote epithelial barrier disruption. J Exp Med. 2023;220:e20230104.","journal-title":"J Exp Med"},{"key":"2852_CR36","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-42760-4","volume":"13","author":"Y Chen","year":"2023","unstructured":"Chen Y, Guo X, Zeng Y, Mo X, Hong S, He H, et al. Oxidative stress induces mitochondrial iron overload and ferroptotic cell death. Sci Rep. 2023;13:15515.","journal-title":"Sci Rep"},{"key":"2852_CR37","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1111\/ejn.16136","volume":"59","author":"M Regoni","year":"2024","unstructured":"Regoni M, Valtorta F, Sassone J. Dopaminergic neuronal death via necroptosis in Parkinson\u2019s disease: a review of the literature. Eur J Neurosci. 2024;59:1079\u201398.","journal-title":"Eur J Neurosci"},{"key":"2852_CR38","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1016\/j.freeradbiomed.2022.08.011","volume":"190","author":"J Xi","year":"2022","unstructured":"Xi J, Zhang Z, Wang Z, Wu Q, He Y, Xu Y, et al. Hinokitiol functions as a ferroptosis inhibitor to confer neuroprotection. Free Radic Biol Med. 2022;190:202\u201315.","journal-title":"Free Radic Biol Med"},{"key":"2852_CR39","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1007\/s12640-020-00272-3","volume":"38","author":"ZB Tong","year":"2020","unstructured":"Tong ZB, Braisted J, Chu PH, Gerhold D. The MT1G gene in LUHMES neurons is a sensitive biomarker of neurotoxicity. Neurotox Res. 2020;38:967\u201378.","journal-title":"Neurotox Res"},{"key":"2852_CR40","doi-asserted-by":"crossref","unstructured":"Mishima E, Nakamura T, Doll S, Proneth B, Fedorova M, Pratt DA, et al. Recommendations for robust and reproducible research on ferroptosis. Nat Rev Mol Cell Biol. 2025;26:615\u201330.","DOI":"10.1038\/s41580-025-00843-2"},{"key":"2852_CR41","doi-asserted-by":"publisher","first-page":"1723","DOI":"10.1089\/ars.2013.5675","volume":"20","author":"LL Dunn","year":"2014","unstructured":"Dunn LL, Midwinter RG, Ni J, Hamid HA, Parish CR, Stocker R. New insights into intracellular locations and functions of heme oxygenase-1. Antioxid Redox Signal. 2014;20:1723\u201342.","journal-title":"Antioxid Redox Signal"},{"key":"2852_CR42","doi-asserted-by":"publisher","first-page":"1888","DOI":"10.3390\/antiox11101888","volume":"11","author":"G Ghajar-Rahimi","year":"2022","unstructured":"Ghajar-Rahimi G, Traylor AM, Mathew B, Bostwick JR, Nebane NM, Zmijewska AA, et al. Identification of cytoprotective small-molecule inducers of heme-oxygenase-1. Antioxid (Basel). 2022;11:1888.","journal-title":"Antioxid (Basel)"},{"key":"2852_CR43","doi-asserted-by":"crossref","unstructured":"Klejborowska G, Scarpellini C, Lanthier C, Augustyns K. Recent advances in the development of synthetic ferroptosis inhibitors. 2024 Medicinal Chemistry Reviews, Vol. 59. MEDI, Inc. Published by American Chemical Society; 2024, p 305\u201328. (2024)","DOI":"10.1021\/mc-2024-vol59.ch14"},{"key":"2852_CR44","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1021\/acschembio.2c00897","volume":"18","author":"M Mallais","year":"2023","unstructured":"Mallais M, Hanson CS, Giray M, Pratt DA. General approach to identify, assess, and characterize inhibitors of lipid peroxidation and associated cell death. ACS Chem Biol. 2023;18:561\u201371.","journal-title":"ACS Chem Biol"},{"key":"2852_CR45","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1016\/j.ejmech.2013.09.020","volume":"74","author":"A Bali","year":"2014","unstructured":"Bali A, Sen U, Peshin T. Synthesis, docking and pharmacological evaluation of novel indole based potential atypical antipsychotics. Eur J Med Chem. 2014;74:477\u201390.","journal-title":"Eur J Med Chem"},{"key":"2852_CR46","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1016\/j.cmet.2008.07.005","volume":"8","author":"A Seiler","year":"2008","unstructured":"Seiler A, Schneider M, Forster H, Roth S, Wirth EK, Culmsee C, et al. Glutathione peroxidase 4 senses and translates oxidative stress into 12\/15-lipoxygenase dependent- and AIF-mediated cell death. Cell Metab. 2008;8:237\u201348.","journal-title":"Cell Metab"},{"key":"2852_CR47","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8","volume":"15","author":"MI Love","year":"2014","unstructured":"Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15:550.","journal-title":"Genome Biol"},{"key":"2852_CR48","doi-asserted-by":"publisher","first-page":"2088","DOI":"10.1021\/acschemneuro.0c00751","volume":"12","author":"EG Lavigne","year":"2021","unstructured":"Lavigne EG, Buttigieg D, Steinschneider R, Burstein ES. Pimavanserin promotes trophic factor release and protects cultured primary dopaminergic neurons exposed to MPP+ in a GDNF-dependent manner. ACS Chem Neurosci. 2021;12:2088\u201398.","journal-title":"ACS Chem Neurosci"},{"key":"2852_CR49","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2020.112355","volume":"199","author":"N Ibrahim","year":"2020","unstructured":"Ibrahim N, Bonnet P, Brion JD, Peyrat JF, Bignon J, Levaique H, et al. Identification of a new series of flavopiridol-like structures as kinase inhibitors with high cytotoxic potency. Eur J Med Chem. 2020;199:112355.","journal-title":"Eur J Med Chem"},{"key":"2852_CR50","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1038\/nchembio711","volume":"1","author":"A Degterev","year":"2005","unstructured":"Degterev A, Huang Z, Boyce M, Li Y, Jagtap P, Mizushima N, et al. Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury. Nat Chem Biol. 2005;1:112\u20139.","journal-title":"Nat Chem Biol"}],"container-title":["Cell Death Discovery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41420-025-02852-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41420-025-02852-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41420-025-02852-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T16:02:56Z","timestamp":1764345776000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41420-025-02852-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,28]]},"references-count":50,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["2852"],"URL":"https:\/\/doi.org\/10.1038\/s41420-025-02852-8","relation":{},"ISSN":["2058-7716"],"issn-type":[{"value":"2058-7716","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,28]]},"assertion":[{"value":"18 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 September 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 October 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 November 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Claire Delehouz\u00e9, Marie-Th\u00e9r\u00e8se Dimanche-Boitrel, Morgane Rousselot and St\u00e9phane Bach are the cofounders, shareholders and members of the scientific advisory board of SeaBeLife Biotech, which is developing novel therapies for treating liver acute disorders and retinal diseases. Peter Goekjian is member of the scientific advisory board of SeaBeLife Biotech. The other authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Patient data and tissue collection were performed under the agreement with the European Network of Research Ethics Committees and French ethic law. The ethical committee, according to the Medical Research Involving Human Subjects Act, reviewed and approved the study. Informed voluntary consent was obtained from every participant of the study: agreements CHU 19 244\u2009C and CNRS 205782. Regarding consent, all patients are INFORMED about the use of their cells for research purposes. Patients could withdraw their consent at any time, leading to the prompt disposal of their tissue and any derived material.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}}],"article-number":"552"}}