Discovery of a Benzamide Derivative That Protects Pancreatic β-Cells against Endoplasmic Reticulum Stress.

ABSTRACT: Endoplasmic reticulum (ER) stress-mediated pancreatic insulin-producing β-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 β-cell protective agents against ER stress-induced dysfunction and death. Through structure-activity relationship optimization, a 3-(N-piperidinyl)methylbenzamide derivative 13d markedly protects β-cells against ER stress-induced dysfunction and death with near 100% maximum rescue activity and an EC₅₀ of 0.032 μM. Compound 13d alleviates ER stress in β-cells by suppressing ER stress-mediated activation of all three branches of unfolded protein response (UPR) and apoptotic genes. Finally, w

SUBMITTER: Duan H 

PROVIDER: S-EPMC5605278 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature