Pastor-Cavada, E; Pardo, LM; Kandil, D; Torres-Fuentes, C; Clarke, SL; Shaban, H;McGlacken, GP; Schellekens, H

2016

November

Scientific Reports

A novel non-peptidic agonist of the ghrelin receptor with orexigenic activity in vivo

Validated

Altmetric: 3 ()

Growth hormone secretagogue Food intake Medicinal chemistry Anorexia cachexia Older adults Mechanisms Secretion Fluorine Peptide Healthy

6

1

13

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.

LONDON

2045-2322

10.1038/srep36456