A Novel Non-Peptidic Agonist of the Ghrelin Receptor with Orexigenic Activity in vivo

Identifier:  imarina:6388902

Handle: https://hdl.handle.net/20.500.11797/imarina6388902

Authors:  Pastor-Cavada, Elena; Pardo, Leticia M; Kandil, Dalia; Torres-Fuentes, Cristina; Clarke, Sarah L; Shaban, Hamdy; McGlacken, Gerard P; Schellekens, Harriet

Abstract:
© The Author(s) 2016. Loss of appetite in the medically ill and ageing populations is a major health problem and a significant symptom in cachexia syndromes, which is the loss of muscle and fat mass. Ghrelin is a gut-derived hormone which can stimulate appetite. Herein we describe a novel, simple, non-peptidic, 2-pyridone which acts as a selective agonist for the ghrelin receptor (GHS-R1a). The small 2-pyridone demonstrated clear agonistic activity in both transfected human cells and mouse hypothalamic cells with endogenous GHS-R1a receptor expression. In vivo tests with the hit compound showed significant increased food intake following peripheral administration, which highlights the potent orexigenic effect of this novel GHS-R1a receptor ligand.