Design and Evaluation of Peptide Dual-Agonists of GLP-1 and NPY2 Receptors for Glucoregulation and Weight Loss with Mitigated Nausea and Emesis
Brandon T. Milliken, Clinton Elfers, Oleg G. Chepurny, Kylie S. Chichura, Ian R. Sweet, Tito Borner, Matthew R. Hayes, Bart C. De Jonghe, George G. Holz, Christian L. Roth, Robert P. Doyle
Abstract
rat and shrew studies of glucoregulation, weight loss, nausea, and emesis. GEP44 in lean and diet-induced obese rats produced greater reduction in body weight compared to Ex-4 without triggering nausea associated behavior. Studies in the shrew demonstrated a near absence of emesis for GEP44 in contrast to Ex-4. Collectively, these data demonstrate that targeting GLP-1R and Y2-R with chimeric single peptides offers a route to new glucoregulatory treatments that are well-tolerated and have improved weight loss when compared directly to Ex-4.
Topics & Concepts
ChemistryWeight lossEndocrinologyAppetiteNauseaReceptorGlucagon-like peptide-1Internal medicinePeptide YYPharmacologyNeuropeptide Y receptorNeuropeptideDiabetes mellitusMedicineType 2 diabetesObesityBiochemistryRegulation of Appetite and ObesityDiabetes Treatment and ManagementPharmacology and Obesity Treatment