Azoramide

Azoramide (CAS No.: 932986-18-0) is a potent, orally active small-molecule modulator of the unfolded protein response (UPR) that is widely utilized in studies of endoplasmic reticulum (ER) stress and proteostasis. Functionally, Azoramide enhances ER protein-folding capacity and upregulates molecular chaperone expression, thereby restoring ER homeostasis and protecting cells from stress-induced dysfunction. Mechanistically, it activates UPR-associated transcriptional programs and promotes phosphorylation of eukaryotic initiation factor 2α, leading to attenuation of global protein synthesis while facilitating adaptive stress responses; it has also been shown to modulate CREB-related signaling pathways to support mitochondrial integrity and prevent apoptosis, particularly in dopaminergic neurons under pathological stress conditions such as those induced by PLA2G6 mutations. In vitro, Azoramide exhibits activity in the low micromolar range, where it dose-dependently induces UPR-responsive reporter genes and increases ER chaperone levels. In vivo, it has demonstrated antidiabetic effects in metabolic disease models, improving insulin sensitivity, glucose homeostasis, and pancreatic β-cell survival under ER stress conditions. As such, Azoramide serves as a valuable chemical probe for investigating ER stress-related signaling networks and is commonly applied in cell-based assays and animal models of neurodegeneration, metabolic disorders, and protein misfolding diseases, with experimental concentrations or dosing regimens tailored to specific study designs.