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

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Pastor-Cavada, Elena
Pardo, Leticia M.
Kandil, Dalia
Torres-Fuentes, Cristina
Clarke, Sarah L.
Shaban, Hamdy
McGlacken, Gerard P.
Schellekens, Harriët
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Nature Publishing Group
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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.
Growth hormone secretagogue , Food intake , Medicinal chemistry , Older adults , Mechanisms , Secretion , Fluorine , Peptide , Healthy , Anorexia-cachexia
Pastor-Cavada, E., Pardo, L. M., Kandil, D., Torres-Fuentes, C., Clarke, S. L., Shaban, H., McGlacken, G. P. and Schellekens, H. (2016) 'A novel non-peptidic agonist of the ghrelin receptor with orexigenic activity in vivo', Scientific Reports, 6, 36456 (13pp). doi:10.1038/srep36456
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