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dc.contributor.authorMoerke, Cen_US
dc.contributor.authorJaco, Ien_US
dc.contributor.authorDewitz, Cen_US
dc.contributor.authorMüller, Ten_US
dc.contributor.authorJacobsen, AVen_US
dc.contributor.authorGautheron, Jen_US
dc.contributor.authorFritsch, Jen_US
dc.contributor.authorSchmitz, Jen_US
dc.contributor.authorBräsen, JHen_US
dc.contributor.authorGünther, Cen_US
dc.contributor.authorMurphy, JMen_US
dc.contributor.authorKunzendorf, Uen_US
dc.contributor.authorMeier, Pen_US
dc.contributor.authorKrautwald, Sen_US
dc.coverage.spatialEnglanden_US
dc.date.accessioned2019-02-20T07:49:32Z
dc.date.issued2019-09en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/30442947en_US
dc.identifier10.1038/s41418-018-0232-2en_US
dc.identifier.citationCell Death Differ, 2019, 26 (9), pp. 1631 - 1645en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3064
dc.identifier.eissn1476-5403en_US
dc.identifier.doi10.1038/s41418-018-0232-2en_US
dc.description.abstractDifferent forms of regulated cell death-like apoptosis and necroptosis contribute to the pathophysiology of clinical conditions including ischemia-reperfusion injury, myocardial infarction, sepsis, and multiple sclerosis. In particular, the kinase activity of the receptor-interacting serine/threonine protein kinase 1 (RIPK1) is crucial for cell fate in inflammation and cell death. However, despite its involvement in pathological conditions, no pharmacologic inhibitor of RIPK1-mediated cell death is currently in clinical use. Herein, we screened a collection of clinical compounds to assess their ability to modulate RIPK1-mediated cell death. Our small-scale screen identified the anti-epilepsy drug Phenhydan® as a potent inhibitor of death receptor-induced necroptosis and apoptosis. Accordingly, Phenhydan® blocked activation of necrosome formation/activation as well as death receptor-induced NF-κB signaling by influencing the membrane function of cells, such as lipid raft formation, thus exerting an inhibitory effect on pathophysiologic cell death processes. By targeting death receptor signaling, the already FDA-approved Phenhydan® may provide new therapeutic strategies for inflammation-driven diseases caused by aberrant cell death.en_US
dc.format.extent1631 - 1645en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.titleThe anticonvulsive Phenhydan® suppresses extrinsic cell death.en_US
dc.typeJournal Article
dcterms.dateAccepted2018-10-30en_US
rioxxterms.versionofrecord10.1038/s41418-018-0232-2en_US
rioxxterms.licenseref.startdate2019-09en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfCell Death Differen_US
pubs.issue9en_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Cell Death and Immunity
pubs.publication-statusPublisheden_US
pubs.volume26en_US
pubs.embargo.termsNot knownen_US
icr.researchteamCell Death and Immunityen_US
dc.contributor.icrauthorMeier, Pascalen_US


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Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/