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10.1021/acs.jmedchem.7b00435 http://scihub22266oqcxt.onion/10.1021/acs.jmedchem.7b00435 C5605278!5605278 !28696115     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=28696115 &cmd=llinks): Failed to open stream: HTTP request failed! 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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)methylbenzamide derivative 13d markedly protects ?-cells against ER stress-induced dysfunction and death with near 100% maximum rescue activity and an EC(50) of 0.032 ?M. 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 ?-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 ): 6191-6204 PMID28696115 show 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)methylbenzamide derivative 13d markedly protects ?-cells against ER stress-induced dysfunction and death with near 100% maximum rescue activity and an EC(50) of 0.032 ?M. 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 ?-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. |Animals [MESH] |Apoptosis/drug effects [MESH] |Benzamides/chemical synthesis/*chemistry/pharmacology [MESH] |Blood Glucose/metabolism [MESH] |Cell Line [MESH] |Cell Survival/drug effects [MESH] |Diabetes Mellitus, Experimental/blood/drug therapy/pathology [MESH] |Endoplasmic Reticulum Stress/*drug effects [MESH] |High-Throughput Screening Assays [MESH] |Humans [MESH] |Hypoglycemic Agents/chemical synthesis/*chemistry/pharmacology [MESH] |Insulin-Secreting Cells/cytology/*drug effects/metabolism [MESH] |Mice, Inbred C57BL [MESH] |Piperidines/chemical synthesis/*chemistry/pharmacology [MESH] |Structure-Activity Relationship [MESH]Discovery of a Benzamide Derivative That Protects Pancreatic ?-Cells a(epmc).pdf DeepDyve Pubget Overpricing