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10.1158/1535-7163.MCT-15-0729-T http://scihub22266oqcxt.onion/10.1158/1535-7163.MCT-15-0729-T C4873341!4873341 !26823493     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=26823493 &cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215       Mol+Cancer+Ther 2016 ; 15 (5 ): 866-76 Nephropedia Template TP {{tp|p=26823493 |t=2016. Posaconazole, a Second-Generation Triazole Antifungal Drug, Inhibits the Hedgehog Signaling Pathway and Progression of Basal Cell Carcinoma |pdf=|usr=}}{{26823493 }} gab.com Text Posaconazole, a Second-Generation Triazole Antifungal Drug, Inhibits the Hedgehog Signaling Pathway and Progression of Basal Cell Carcinoma JO: Mol Cancer Ther http://www.kidney.de/pget.php?&tw=1&pmid=26823493 #FOAvip Deregulation of Hedgehog (Hh) pathway signaling has been associated with the pathogenesis of various malignancies, including basal cell carcinomas (BCC). Inhibitors of the Hh pathway currently available or under clinical investigation all bind and antagonize Smoothened (SMO), inducing a marked but transient clinical response. Tumor regrowth and therapy failure were attributed to mutations in the binding site of these small-molecule SMO antagonists. The antifungal itraconazole was demonstrated to be a potent SMO antagonist with a distinct mechanism of action from that of current SMO inhibitors. However, itraconazole represents a suboptimal therapeutic option due to its numerous drug-drug interactions. Here, we show that posaconazole, a second-generation triazole antifungal with minimal drug-drug interactions and a favorable side-effect profile, is also a potent inhibitor of the Hh pathway that functions at the level of SMO. We demonstrate that posaconazole inhibits the Hh pathway by a mechanism distinct from that of cyclopamine and other cyclopamine-competitive SMO antagonists but, similar to itraconazole, has robust activity against drug-resistant SMO mutants and inhibits the growth of Hh-dependent BCC in vivo Our results suggest that posaconazole, alone or in combination with other Hh pathway antagonists, may be readily tested in clinical studies for the treatment of Hh-dependent cancers. Mol Cancer Ther; 15(5); 866-76. ©2016 AACR. Twit Text FOAVip Posaconazole, a Second-Generation Triazole Antifungal Drug, Inhibits the Hedgehog Signaling Pathway and Progression of Basal Cell Carcinoma ????Mol Cancer Ther http://www.kidney.de/pget.php?&tw=1&pmid=26823493 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26823493 #FOAvip English Wikipedia <ref>{{Cite pmid|26823493 }}</ref> Posaconazole, a Second-Generation Triazole Antifungal Drug, Inhibits the Hedgehog Signaling Pathway and Progression of Basal Cell Carcinoma #MMPMID26823493 Chen B ; Trang V ; Lee A ; Williams NS ; Wilson AN ; Epstein EH Jr ; Tang JY ; Kim J Mol Cancer Ther 2016[May]; 15 (5 ): 866-76 PMID26823493 show ga Deregulation of Hedgehog (Hh) pathway signaling has been associated with the pathogenesis of various malignancies, including basal cell carcinomas (BCC). Inhibitors of the Hh pathway currently available or under clinical investigation all bind and antagonize Smoothened (SMO), inducing a marked but transient clinical response. Tumor regrowth and therapy failure were attributed to mutations in the binding site of these small-molecule SMO antagonists. The antifungal itraconazole was demonstrated to be a potent SMO antagonist with a distinct mechanism of action from that of current SMO inhibitors. However, itraconazole represents a suboptimal therapeutic option due to its numerous drug-drug interactions. Here, we show that posaconazole, a second-generation triazole antifungal with minimal drug-drug interactions and a favorable side-effect profile, is also a potent inhibitor of the Hh pathway that functions at the level of SMO. We demonstrate that posaconazole inhibits the Hh pathway by a mechanism distinct from that of cyclopamine and other cyclopamine-competitive SMO antagonists but, similar to itraconazole, has robust activity against drug-resistant SMO mutants and inhibits the growth of Hh-dependent BCC in vivo Our results suggest that posaconazole, alone or in combination with other Hh pathway antagonists, may be readily tested in clinical studies for the treatment of Hh-dependent cancers. Mol Cancer Ther; 15(5); 866-76. ©2016 AACR. |Animals [MESH] |Antifungal Agents/pharmacology [MESH] |Antineoplastic Agents/*pharmacology [MESH] |Carcinoma, Basal Cell/drug therapy/*metabolism/pathology [MESH] |Cell Line, Tumor [MESH] |Disease Models, Animal [MESH] |Gene Knockout Techniques [MESH] |Hedgehog Proteins/*metabolism [MESH] |Humans [MESH] |Mice [MESH] |Signal Transduction/*drug effects [MESH] |Skin Neoplasms/drug therapy/*metabolism/pathology [MESH] |Smoothened Receptor/genetics/metabolism [MESH] |Triazoles/*pharmacology [MESH]Posaconazole, a Second-Generation Triazole Antifungal Drug, Inhibits t(epmc).pdf DeepDyve Pubget Overpricing