Editors' ChoicePharmacology

Improving ER function

Sci. Signal.  23 Jun 2015:
Vol. 8, Issue 382, pp. ec171
DOI: 10.1126/scisignal.aac8281

Disruption in ER function and chronic ER stress are associated with pathologies that range from diabetes and neurodegenerative diseases to cancer and inflammation. Here, Fu et al. designed two high-throughput assays that test distinct endoplasmic reticulum (ER) functions, ER protein folding and ER chaperone capacity. With these assays, they identified a candidate compound, azoramide, that exhibits antidiabetic activity in mouse models of obesity and exhibited improved ER protein folding and increased ER chaperone capacity in their assays.

S. Fu, A. Yalcin, G. Y. Lee, P. Li, J. Fan, A. P. Arruda, B. M. Pers, M. Yilmaz, K. Eguchi, G. S. Hotamisligil, Phenotypic assays identify azoramide as a small-molecule modulator of the unfolded protein response with antidiabetic activity. Sci. Transl. Med. 7, 292ra98 (2015). [Abstract]