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10.1038/cddis.2017.298 http://scihub22266oqcxt.onion/10.1038/cddis.2017.298 C5520944!5520944 !28661484     free     free     free Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\28661484 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Cell+Death+Dis 2017 ; 8 (6 ): e2904 Nephropedia Template TP {{tp|p=28661484 |t=2017. Sorafenib tosylate inhibits directly necrosome complex formation and protects in mouse models of inflammation and tissue injury |pdf=|usr=}}{{28661484 }} gab.com Text Sorafenib tosylate inhibits directly necrosome complex formation and protects in mouse models of inflammation and tissue injury JO: Cell Death Dis http://www.kidney.de/pget.php?&tw=1&pmid=28661484 #FOAvip 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-?B 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. Twit Text FOAVip Sorafenib tosylate inhibits directly necrosome complex formation and protects in mouse models of inflammation and tissue injury ????Cell Death Dis http://www.kidney.de/pget.php?&tw=1&pmid=28661484 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28661484 #FOAvip English Wikipedia <ref>{{Cite pmid|28661484 }}</ref> Sorafenib tosylate inhibits directly necrosome complex formation and protects in mouse models of inflammation and tissue injury #MMPMID28661484 Martens S ; Jeong M ; Tonnus W ; Feldmann F ; Hofmans S ; Goossens V ; Takahashi N ; Bräsen JH ; Lee EW ; Van der Veken P ; Joossens J ; Augustyns K ; Fulda S ; Linkermann A ; Song J ; Vandenabeele P Cell Death Dis 2017[Jun]; 8 (6 ): e2904 PMID28661484 show ga 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-?B 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. |Animals [MESH] |Apoptosis/drug effects/genetics [MESH] |Cell Death/drug effects [MESH] |Disease Models, Animal [MESH] |Humans [MESH] |Inflammation/*drug therapy/genetics/pathology [MESH] |Mice [MESH] |Necrosis/*genetics/pathology [MESH] |Niacinamide/administration & dosage/analogs & derivatives [MESH] |Phenylurea Compounds/administration & dosage [MESH] |Phosphorylation/genetics [MESH] |Protein Kinases/*genetics [MESH] |Receptor-Interacting Protein Serine-Threonine Kinases/*genetics [MESH] |Reperfusion Injury/chemically induced/genetics/pathology [MESH] |Sorafenib [MESH]Sorafenib tosylate inhibits directly necrosome complex formation and p(epmc).pdf DeepDyve Pubget Overpricing