Small Molecule Ghrelin Receptor Inverse Agonists and Antagonists

• Published in: Journal of medicinal chemistry Vol. 57; no. 21; pp. 8671 - 8691
• Main Authors: Cameron, Kimberly O, Bhattacharya, Samit K, Loomis, A. Katrina
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 13-11-2014
• Subjects: Acyltransferases - genetics; Animals; Drug Industry; Eating - drug effects; Ghrelin - genetics; Ghrelin - pharmacology; Glucose - metabolism; Homeostasis - drug effects; Humans; Obesity - drug therapy; Pancreas - drug effects; Pancreas - physiology; Rats; Receptors, Ghrelin - agonists; Receptors, Ghrelin - antagonists & inhibitors; Receptors, Ghrelin - genetics
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm5003183

Ghrelin is an endogenous peptide hormone secreted primarily by the stomach and is involved in a number of physiological processes including growth hormone secretion, food intake, as well as energy and glucose homeostasis. The physiological actions of ghrelin are mediated through the growth hormone secretagogue receptor 1a (ghrelin receptor), a peptidic G-protein-coupled receptor. This target has attracted much interest, as agents that block ghrelin’s actions on its receptor are anticipated to be pharmaceutical interventions for a number of diseases. This review provides an overview of ghrelin biology with a focus on metabolic diseases and summarizes recent medicinal chemistry programs aimed at delivering small molecule ghrelin receptor antagonists and inverse agonists to the clinic.