Grant: Project Grant

Diabetes represents a significant threat to the health of Canadians and an untenable burden to the Canadian economy and health-care system. It is estimated that by 2020 one in three Canadians will suffer from diabetes and that the associated costs to the health care system will rise to $16 billion annually. Glucocorticoids are potent anti-inflammatory and immunosuppressive drugs used to treat rheumatoid arthritis, inflammatory bowel disease, and cancer among other conditions. Unfortunately, a common side effect of prolonged glucocorticoid use is the development of diabetes. In previous studies using mouse models we have shown that this deleterious side effect can be dissociated from the beneficial anti-inflammatory effects of glucocorticoid drugs by modulating the function of LXRb, a regulatory protein, and also developed a small molecule, LO-520, that selectively interacts with LXRb. We believe this finding represents a potential therapy for the prevention of diabetes and are now poised to develop a new generation of anti-diabetic drugs. In this proposal we will optimize the drug-like properties of molecules related to LO-520 and identify a pre-clinical candidate for the preventative treatment of glucocorticoid-induced diabetes.