Progress in small molecule and biologic therapeutics targeting ghrelin signaling

Kayleigh R. McGovern, Joseph E. Darling, James L Hougland

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)465-480
Number of pages16
JournalMini-Reviews in Medicinal Chemistry
Volume16
Issue number6
StatePublished - Apr 1 2016

Fingerprint

Ghrelin
Therapeutics
Ghrelin Receptor
Physiological Phenomena
Prader-Willi Syndrome
Appetite Regulation
Acyltransferases
Peptide Hormones
Adiposity
Appetite
Type 2 Diabetes Mellitus
Homeostasis
Obesity
Body Weight

Keywords

  • Diabetes
  • Ghrelin
  • Ghrelin O-acyltransferase
  • GHS-R1a receptor
  • Membrane-bound O-acyltransferase
  • Obesity
  • Prader-Willi syndrome
  • Spiegelmer

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

Cite this

Progress in small molecule and biologic therapeutics targeting ghrelin signaling. / McGovern, Kayleigh R.; Darling, Joseph E.; Hougland, James L.

In: Mini-Reviews in Medicinal Chemistry, Vol. 16, No. 6, 01.04.2016, p. 465-480.

Research output: Contribution to journalArticle

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