Azoramide

Azoramide is a potent, orally active small-molecule modulator of the unfolded protein response (UPR). Azoramide improves ER protein folding and elevates ER chaperone capacity, which together protects cells against ER stress. Azoramide alleviates PLA2G6 mutant-induced ER stress through modulating unfolded protein response, and enhances the CERB signaling to rescue mitochondrial function, thereby preventing apoptosis of DA neurons. Azoramide has antidiabetic activity^[1][2]. In Vitro: Azoramide (0.01-100 µM; 0-24 h; Huh7 cells) regulates ER folding and secretion capacity without inducing ER stress^[1].
Azoramide (15 µM; 2-16 h; Huh7 cells) protects cells from induced ER stress. Azoramide counteracts Tunicamycin (Tm, HY-A0098)-induced ATF6LD-Cluc secretion and Tm-induced decrease of ASGR-Cluc secretion. Azoramide suppresses Tm-induced GRP78 and CHOP protein expression^[1].
Azoramide (15 µM; 2-16 h; Hepa 1-6 cells) alters ER calcium homeostasis and retains a greater fraction of Ca²⁺ in the ER^[1].
Azoramide (0-10 µM; 5 d) attenuates loss of PLA2G6^D331Y/D331Y iPSC-derived midbrain DA neurons^[2].
Azoramide (10 µM; 5 d) reduces the increase in ROS and ameliorates the decline in mitochondrial membrane potential in PLA2G6^D331Y/D331Y midbrain DA neurons^[2].
Azoramide (10 µM; 0-30 d) suppresses mitochondrial fragmentation in PLA2G6^D331Y/D331Y midbrain DA neurons^[2].
In Vivo: Azoramide (150 mg/kg; p.o.; daily, for 7 d; Huh7 cells; ob/ob mice) improves glucose homeostasis in mice with genetic obesity and preserves beta cell function and survival during metabolic ER stress^[1].