Open AccessAdvances in the Development of Nonpeptide Small Molecules Targeting Ghrelin Receptor
Author(s) -
Gianfabio Giorgioni,
Fabio Del Bello,
Wilma Quaglia,
Luca Botticelli,
Carlo Cifani,
Emanuela Micioni Di Bonaventura,
Maria Vittoria Micioni Di Bonaventura,
Alessandro Piergentili
Publication year - 2022
Publication title -
journal of medicinal chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.01
H-Index - 261
eISSN - 1520-4804
pISSN - 0022-2623
DOI - 10.1021/acs.jmedchem.1c02191
Subject(s) - ghrelin , growth hormone secretagogue receptor , chemistry , receptor , inverse agonist , secretagogue , energy homeostasis , glucose homeostasis , pharmacology , endocrinology , medicine , antagonist , biochemistry , insulin , insulin resistance , biology
Ghrelin is an octanoylated peptide acting by the activation of the growth hormone secretagogue receptor, namely, GHS-R1a. The involvement of ghrelin in several physiological processes, including stimulation of food intake, gastric emptying, body energy balance, glucose homeostasis, reduction of insulin secretion, and lipogenesis validates the considerable interest in GHS-R1a as a promising target for the treatment of numerous disorders. Over the years, several GHS-R1a ligands have been identified and some of them have been extensively studied in clinical trials. The recently resolved structures of GHS-R1a bound to ghrelin or potent ligands have provided useful information for the design of new GHS-R1a drugs. This perspective is focused on the development of recent nonpeptide small molecules acting as GHS-R1a agonists, antagonists, and inverse agonists, bearing classical or new molecular scaffolds, as well as on radiolabeled GHS-R1a ligands developed for imaging. Moreover, the pharmacological effects of the most studied ligands have been discussed.