DC Field | Value | Language |
---|---|---|
dc.contributor.author | S Martens | - |
dc.contributor.author | M Jeong | - |
dc.contributor.author | W Tonnus | - |
dc.contributor.author | F Feldmann | - |
dc.contributor.author | S Hofmans | - |
dc.contributor.author | V Goossens | - |
dc.contributor.author | N Takahashi | - |
dc.contributor.author | J H Brasen | - |
dc.contributor.author | Eun Woo Lee | - |
dc.contributor.author | P V Veken | - |
dc.contributor.author | J Joossens | - |
dc.contributor.author | K Augustyns | - |
dc.contributor.author | S Fulda | - |
dc.contributor.author | A Linkermann | - |
dc.contributor.author | J Song | - |
dc.contributor.author | P Vandenabeele | - |
dc.date.accessioned | 2017-08-29 | - |
dc.date.available | 2017-08-29 | - |
dc.date.issued | 2017 | - |
dc.identifier.issn | 2041-4889 | - |
dc.identifier.uri | https://oak.kribb.re.kr/handle/201005/17233 | - |
dc.description.abstract | Necroptosis contributes to the pathophysiology of several inflammatory, infectious and degenerative disorders. TNF-induced necroptosis involves activation of the receptor-interacting protein kinases 1 and 3 (RIPK1/3) in a necrosome complex, eventually leading to the phosphorylation and relocation of mixed lineage kinase domain like protein (MLKL). Using a high-content screening of small compounds and FDA-approved drug libraries, we identified the anti-cancer drug Sorafenib tosylate as a potent inhibitor of TNF-dependent necroptosis. Interestingly, Sorafenib has a dual activity spectrum depending on its concentration. In murine and human cell lines it induces cell death, while at lower concentrations it inhibits necroptosis, without affecting NF-κB activation. Pull down experiments with biotinylated Sorafenib show that it binds independently RIPK1, RIPK3 and MLKL. Moreover, it inhibits RIPK1 and RIPK3 kinase activity. In vivo Sorafenib protects against TNF-induced systemic inflammatory response syndrome (SIRS) and renal ischemia-reperfusion injury (IRI). Altogether, we show that Sorafenib can, next to the reported Braf/Mek/Erk and VEGFR pathways, also target the necroptotic pathway and that it can protect in an acute inflammatory RIPK1/3-mediated pathology. | - |
dc.publisher | Springer-Nature Pub Group | - |
dc.title | Sorafenib tosylate inhibits directly necrosome complex formation and protects in mouse models of inflammation and tissue injury | - |
dc.title.alternative | Sorafenib tosylate inhibits directly necrosome complex formation and protects in mouse models of inflammation and tissue injury | - |
dc.type | Article | - |
dc.citation.title | Cell Death & Disease | - |
dc.citation.number | 6 | - |
dc.citation.endPage | e2904 | - |
dc.citation.startPage | e2904 | - |
dc.citation.volume | 8 | - |
dc.contributor.affiliatedAuthor | Eun Woo Lee | - |
dc.contributor.alternativeName | Martens | - |
dc.contributor.alternativeName | 정만형 | - |
dc.contributor.alternativeName | Tonnus | - |
dc.contributor.alternativeName | Feldmann | - |
dc.contributor.alternativeName | Hofmans | - |
dc.contributor.alternativeName | Goossens | - |
dc.contributor.alternativeName | Takahashi | - |
dc.contributor.alternativeName | Brasen | - |
dc.contributor.alternativeName | 이은우 | - |
dc.contributor.alternativeName | Veken | - |
dc.contributor.alternativeName | Joossens | - |
dc.contributor.alternativeName | Augustyns | - |
dc.contributor.alternativeName | Fulda | - |
dc.contributor.alternativeName | Linkermann | - |
dc.contributor.alternativeName | 송재환 | - |
dc.contributor.alternativeName | Vandenabeele | - |
dc.identifier.bibliographicCitation | Cell Death & Disease, vol. 8, no. 6, pp. e2904-e2904 | - |
dc.identifier.doi | 10.1038/cddis.2017.298 | - |
dc.description.journalClass | Y | - |
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