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10.1021/acs.jmedchem.7b00435 http://scihub22266oqcxt.onion/10.1021/acs.jmedchem.7b00435 C5605278!5605278!28696115     free     free     free Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 253.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       J+Med+Chem 2017 ; 60 (14): 6191-204 Nephropedia Template TP {{tp|p=28696115|t=2017. Discovery of a benzamide derivative that protects pancreatic ?-cells against endoplasmic reticulum stress |pdf=|usr=}}{{28696115}} gab.com Text Discovery of a benzamide derivative that protects pancreatic -cells against endoplasmic reticulum stress JO: J Med Chem http://www.kidney.de/pget.php?&tw=1&pmid=28696115 #FOAvip Endoplasmic reticulum (ER) stress-mediated pancreatic insulin-producing ?-cell dysfunction and death are critical elements in the onset and progression of both type 1 and type 2 diabetes. Here, through cell-based high throughput screening we identified benzamide derivatives as a novel class of ?-cell protective agents against ER stress-induced dysfunction and death. Through structure-activity relationship optimization, a 3-(N-piperidinyl)methyl benzamide derivative 13d markedly protects ?-cells against ER stress-induced dysfunction and death with near 100% maximum rescue activity and an EC50 value of 0.032 µM. Compound 13d alleviates ER stress in ?-cells by suppressing ER stress-mediated activation of all three branches of unfolded protein response (UPR) and apoptotic genes. Finally, we show that 13d significantly lowers blood glucose levels and increases concomitant b-cell survival and number in a streptozotocin-induced diabetic mouse model. Identification of ?-cell-protective small molecules against ER stress provides a new promising modality for the treatment of diabetes. Twit Text FOAVip Discovery of a benzamide derivative that protects pancreatic -cells against endoplasmic reticulum stress ????J Med Chem http://www.kidney.de/pget.php?&tw=1&pmid=28696115 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28696115 #FOAvip English Wikipedia <ref>{{Cite pmid|28696115}}</ref> Discovery of a benzamide derivative that protects pancreatic ?-cells against endoplasmic reticulum stress #MMPMID28696115 Duan H; Li Y; Arora D; Xu D; Lim HY; Wang W J Med Chem 2017[Jul]; 60 (14): 6191-204 PMID28696115show ga Endoplasmic reticulum (ER) stress-mediated pancreatic insulin-producing ?-cell dysfunction and death are critical elements in the onset and progression of both type 1 and type 2 diabetes. Here, through cell-based high throughput screening we identified benzamide derivatives as a novel class of ?-cell protective agents against ER stress-induced dysfunction and death. Through structure-activity relationship optimization, a 3-(N-piperidinyl)methyl benzamide derivative 13d markedly protects ?-cells against ER stress-induced dysfunction and death with near 100% maximum rescue activity and an EC50 value of 0.032 µM. Compound 13d alleviates ER stress in ?-cells by suppressing ER stress-mediated activation of all three branches of unfolded protein response (UPR) and apoptotic genes. Finally, we show that 13d significantly lowers blood glucose levels and increases concomitant b-cell survival and number in a streptozotocin-induced diabetic mouse model. Identification of ?-cell-protective small molecules against ER stress provides a new promising modality for the treatment of diabetes. äDiscovery of a benzamide derivative that protects pancreatic ?-cells a(epmc).pdf DeepDyve Pubget Overpricing