The 1,2,4-triazole as a scaffold for the design of ghrelin receptor ligands: Development of JMV 2959, a potent antagonist

Aline Moulin, Luc Brunel, Damien Boeglin, Luc Demange, Johanne Ryan, Celine M'Kadmi, Severine Denoyelle, Jean Martinez, Jean-Alain Fehrentz

Research output: Contribution to journalReview ArticleOtherpeer-review

39 Citations (Scopus)

Abstract

Ghrelin is a 28-residue peptide acylated with an n-octanoyl group on the Ser 3 residue, predominantly produced by the stomach. Ghrelin displays strong growth hormone (GH) releasing activity, which is mediated by the activation of the so-called GH secretagogue receptor type 1a (GHS-R1a). Given the wide spectrum of biological activities of Ghrelin in neuroendocrine and metabolic pathways, many research groups, including our group, developed synthetic peptide, and nonpeptide GHS-R1a ligands, acting as agonists, partial agonists, antagonists, or inverse agonists. In this highlight article, we will focus on the discovery of a GHS-R1a antagonist compound, JMV 2959, which has been extensively studied in different in vitro and in vivo models. We will first describe the peptidomimetic approach that led us to discover this compound. Then we will review the results obtained with this compound in different studies in the fields of food intake and obesity, addictive behaviors, hyperactivity and retinopathy.

Original languageEnglish
Pages (from-to)301-314
Number of pages14
JournalAmino Acids
Volume44
Issue number2
DOIs
Publication statusPublished - Feb 2013
Externally publishedYes

Keywords

  • 1,2,4-Triazole
  • Addiction
  • Antagonist
  • Anti-obesity
  • Ghrelin receptor
  • Peptidomimetic

Cite this