Quinolones Modulate Ghrelin Receptor Signaling: Potential for a Novel Small Molecule Scaffold in the Treatment of Cachexia

International Journal of Molecular Sciences
Cristina Torres-FuentesHarriët Schellekens

Abstract

Cachexia is a metabolic wasting disorder characterized by progressive weight loss, muscle atrophy, fatigue, weakness, and appetite loss. Cachexia is associated with almost all major chronic illnesses including cancer, heart failure, obstructive pulmonary disease, and kidney disease and significantly impedes treatment outcome and therapy tolerance, reducing physical function and increasing mortality. Current cachexia treatments are limited and new pharmacological strategies are needed. Agonists for the growth hormone secretagogue (GHS-R1a), or ghrelin receptor, prospectively regulate the central regulation of appetite and growth hormone secretion, and therefore have tremendous potential as cachexia therapeutics. Non-peptide GHS-R1a agonists are of particular interest, especially given the high gastrointestinal degradation of peptide-based structures, including that of the endogenous ligand, ghrelin, which has a half-life of only 30 min. However, few compounds have been reported in the literature as non-peptide GHS-R1a agonists. In this paper, we investigate the in vitro potential of quinolone compounds to modulate the GHS-R1a in both transfected human cells and mouse hypothalamic cells. These chemically synthesized compounds dem...Continue Reading

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Citations

Sep 24, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Cristina Torres-FuentesHarriet Schellekens
Sep 23, 2021·Science Translational Medicine·Mark L KovlerDavid J Hackam
Dec 22, 2021·Journal of Neuroendocrinology·Mitchell Ty RinguetSebastian George Barton Furness

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Methods Mentioned

BETA
acylation
Fluorescence

Software Mentioned

SPSS
GraphPad Prism
GraphPAD
INCell Analyzer Developer Toolbox

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