Characterization of a Lead Compound Targeting LXRβ for the Treatment of Glucocorticoid-induced Diabetes

A known cause of diabetes is the long-term use of glucocorticoid (GC) drugs which are commonly used to treat chronic inflammation. Our lab has found that co-treatment of GC drugs with an LXRβ antagonist can decrease GC-induced diabetes. Herein, we characterize the pharmacokinetics of a pre-clinical lead candidate drug (LO520) targeting LXRβ that could be used along with GC therapy to prevent the diabetogenic side effects of GC drugs. LO520 demonstrated receptor specificity towards LXRβ in both murine and human LXR plasmid-based expression systems and significantly reduced plasma glucose levels when dosed in the presence of GC drug (dexamethasone, Dex) without altering the desired immunosuppressive effect. Future studies will need to investigate the molecular mechanisms of LO520 in regulating gluconeogenesis and whether the use of LO520 will impact reverse cholesterol transport and the development of atherosclerosis.M.Sc