hexarelin and macimorelin

New growth hormone secretagogue (GHS) analogues were synthesized and evaluated for growth hormone releasing activity. This series derived from EP-51389 is based on a gem-diamino structure. Compounds that exhibited higher in vivo GH-releasing potency than hexarelin in rat (subcutaneous administration) were then tested per os in beagle dogs and for their binding affinity to human pituitary GHS receptors and to hGHS-R 1a. Compound 7 (JMV 1843, H-Aib-(d)-Trp-(d)-gTrp-formyl) showed high potency in these tests and was selected for clinical studies.(1)

Topics: Administration, Oral; Adult; Animals; Animals, Newborn; Binding, Competitive; Cell Line; Dogs; Female; Growth Hormone; Humans; In Vitro Techniques; Indoles; Injections, Subcutaneous; Male; Membranes; Middle Aged; Oligopeptides; Pituitary Gland; Radioligand Assay; Rats; Rats, Sprague-Dawley; Receptors, Cell Surface; Receptors, G-Protein-Coupled; Receptors, Ghrelin; Tryptophan

EP1572 UMV1843 [Aib-DTrp-DgTrp-CHO]) is a new peptido-mimetic GH secretagogue (GHS) showing binding potency to the GHS-receptor in animal and human tissues similar to that of ghrelin and peptidyl GHS. EP1572 induces marked GH increase after s.c. administration in neonatal rats. Preliminary data in 2 normal young men show that: 1) acute i.v. EP1572 administration (1.0 microg/kg) induces strong and selective increase of GH levels; 2) single oral EP1572 administration strongly and reproducibly increases GH levels even after a dose as low as 0.06 mg/kg. Thus, EP1572 is a new peptido-mimetic GHS with potent and selective GH-releasing activity.

Topics: Adult; Animals; Binding, Competitive; Dose-Response Relationship, Drug; Ghrelin; Growth Hormone; Human Growth Hormone; Humans; Indoles; Male; Oligopeptides; Peptide Hormones; Pituitary Gland; Rats; Tryptophan