Protego Biopharma Inc. and Scripps Research Institute have identified serine/threonine kinase/endoribonuclease IRE1 (ERN1) activators reported to be useful for the treatment of diabetes, myocardial infarction, nonalcoholic fatty liver disease (NAFLD), Parkinson's disease, retinal degeneration, atherosclerosis, Gaucher disease and Alzheimer's disease, among others.