Targeting the ghrelin receptor: orally active GHS and cortistatin analogs.
Ghrelin has been discovered as a natural ligand of the receptor specific for synthetic GH secretagogues (GHS). Ghrelin as well as synthetic GHS not only possess a remarkable GH-releasing activity but are also endowed with other endocrine and nonendocrine activities including orexigenic action, influence on gastro-enteropancreatic functions, and cardiovascular and anti-proliferative effects. Based on these data, particular effort has been focused on the isolation of new putative natural ligands of the GHS-receptors (GHS-R) and on the identification of synthetic compounds endowed with agonistic or antagonistic activity. For instance, ghrelin analogs acting as agonists or antagonists would be able to enhance or reduce appetite and food intake; these molecules would receive obvious interest for treatment of eating disorders and obesity, respectively. Ghrelin and its orally active, agonistic analogs could have prespectives for diagnosis and treatment of GH insufficiency. In this context, EP1572, a selective, orally active, peptidomimetic GHS as well as cortistatin, another putative, natural ligand of the GHS-R, and its analogs, are currently under investigation.
Deghenghi
Romano
R
Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Italy. hexarelin@bluewin.ch
Broglio
Fabio
F
Papotti
Mauro
M
Muccioli
Giampiero
G
Ghigo
Ezio
E
D000818:Animals; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D013006:Growth Hormone / Q000378:metabolism; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D007211:Indoles; D008024:Ligands; D009479:Neuropeptides / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D054440:Receptors, Ghrelin; D014364:Tryptophan / Q000031:analogs & derivatives
D007211:Indoles; D008024:Ligands; D009479:Neuropeptides; D009842:Oligopeptides; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; C099323:cortistatin; D019382:Human Growth Hormone; C582727:macimorelin; D014364:Tryptophan; D013006:Growth Hormone