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10.18632/oncotarget.11814 http://scihub22266oqcxt.onion/10.18632/oncotarget.11814 C5342060!5342060!27602582     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       Oncotarget 2016 ; 7 (45): 74380-92 Nephropedia Template TP {{tp|p=27602582|t=2016. Discovery and clinical introduction of first-in-class imipridone ONC201 |pdf=|usr=}}{{27602582}} gab.com Text Discovery and clinical introduction of first-in-class imipridone ONC201 JO: Oncotarget http://www.kidney.de/pget.php?&tw=1&pmid=27602582 #FOAvip ONC201 is the founding member of a novel class of anti-cancer compounds called imipridones that is currently in Phase II clinical trials in multiple advanced cancers. Since the discovery of ONC201 as a p53-independent inducer of TRAIL gene transcription, preclinical studies have determined that ONC201 has anti-proliferative and pro-apoptotic effects against a broad range of tumor cells but not normal cells. The mechanism of action of ONC201 involves engagement of PERK-independent activation of the integrated stress response, leading to tumor upregulation of DR5 and dual Akt/ERK inactivation, and consequent Foxo3a activation leading to upregulation of the death ligand TRAIL. ONC201 is orally active with infrequent dosing in animals models, causes sustained pharmacodynamic effects, and is not genotoxic. The first-in-human clinical trial of ONC201 in advanced aggressive refractory solid tumors confirmed that ONC201 is exceptionally well-tolerated and established the recommended phase II dose of 625 mg administered orally every three weeks defined by drug exposure comparable to efficacious levels in preclinical models. Clinical trials are evaluating the single agent efficacy of ONC201 in multiple solid tumors and hematological malignancies and exploring alternative dosing regimens. In addition, chemical analogs that have shown promise in other oncology indications are in pre-clinical development. In summary, the imipridone family that comprises ONC201 and its chemical analogs represent a new class of anti-cancer therapy with a unique mechanism of action being translated in ongoing clinical trials. Twit Text FOAVip Discovery and clinical introduction of first-in-class imipridone ONC201 ????Oncotarget http://www.kidney.de/pget.php?&tw=1&pmid=27602582 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=27602582 #FOAvip English Wikipedia <ref>{{Cite pmid|27602582}}</ref> Discovery and clinical introduction of first-in-class imipridone ONC201 #MMPMID27602582 Allen JE; Kline CLB; Prabhu VV; Wagner J; Ishizawa J; Madhukar N; Lev A; Baumeister M; Zhou L; Lulla A; Stogniew M; Schalop L; Benes C; Kaufman HL; Pottorf RS; Nallaganchu BR; Olson GL; Al-Mulla F; Duvic M; Wu GS; Dicker DT; Talekar MK; Lim B; Elemento O; Oster W; Bertino J; Flaherty K; Wang ML; Borthakur G; Andreeff M; Stein M; El-Deiry WS Oncotarget 2016[Nov]; 7 (45): 74380-92 PMID27602582show ga ONC201 is the founding member of a novel class of anti-cancer compounds called imipridones that is currently in Phase II clinical trials in multiple advanced cancers. Since the discovery of ONC201 as a p53-independent inducer of TRAIL gene transcription, preclinical studies have determined that ONC201 has anti-proliferative and pro-apoptotic effects against a broad range of tumor cells but not normal cells. The mechanism of action of ONC201 involves engagement of PERK-independent activation of the integrated stress response, leading to tumor upregulation of DR5 and dual Akt/ERK inactivation, and consequent Foxo3a activation leading to upregulation of the death ligand TRAIL. ONC201 is orally active with infrequent dosing in animals models, causes sustained pharmacodynamic effects, and is not genotoxic. The first-in-human clinical trial of ONC201 in advanced aggressive refractory solid tumors confirmed that ONC201 is exceptionally well-tolerated and established the recommended phase II dose of 625 mg administered orally every three weeks defined by drug exposure comparable to efficacious levels in preclinical models. Clinical trials are evaluating the single agent efficacy of ONC201 in multiple solid tumors and hematological malignancies and exploring alternative dosing regimens. In addition, chemical analogs that have shown promise in other oncology indications are in pre-clinical development. In summary, the imipridone family that comprises ONC201 and its chemical analogs represent a new class of anti-cancer therapy with a unique mechanism of action being translated in ongoing clinical trials. äDiscovery and clinical introduction of first-in-class imipridone ONC20(epmc).pdf DeepDyve Pubget Overpricing