title: Progress in Small Molecule and Biologic Therapeutics Targeting Ghrelin Signaling.
abstract: Ghrelin is a circulating peptide hormone involved in regulation of a wide array of physiological processes. As an endogenous ligand for growth hormone secretagogue receptor (GHSR1a), ghrelin is responsible for signaling involved in energy homeostasis, including appetite stimulation, glucose metabolism, insulin signaling, and adiposity. Ghrelin has also been implicated in modulation of several neurological processes. Dysregulation of ghrelin signaling is implicated in diseases related to these pathways, including obesity, type II diabetes, and regulation of appetite and body weight in patients with Prader-Willi syndrome. Multiple steps in the ghrelin signaling pathway are available for targeting in the development of therapeutics for these diseases. Agonists and antagonists of GHS-R1a have been widely studied and have shown varying levels of effectiveness within ghrelin-related physiological pathways. Agents targeting ghrelin directly, either through depletion of ghrelin levels in circulation or inhibitors of ghrelin O-acyltransferase whose action is required for ghrelin to become biologically active, are receiving increasing attention as potential therapeutic options. We discuss the approaches utilized to target ghrelin signaling and highlight the current challenges toward developing small-molecule agents as potential therapeutics for ghrelin-related diseases.
authors.forename: Kayleigh R
authors.initials: KR
authors.lastname: McGovern
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Darling
authors.affiliation: Department of Chemistry, Syracuse University, Syracuse, NY, USA. hougland@syr.edu.
authors.forename: James L
authors.initials: JL
authors.lastname: Hougland
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001069:Appetite Regulation / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D055808:Drug Discovery; D054439:Ghrelin / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D058990:Molecular Targeted Therapy; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism; D011218:Prader-Willi Syndrome / Q000188:drug therapy* / Q000378:metabolism; D054440:Receptors, Ghrelin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D054439:Ghrelin; D054440:Receptors, Ghrelin; D054852:Small Molecule Libraries