Study wrapper · #229
A new series of highly potent growth hormone-releasing peptides derived from ipamorelin.
Editor's note
Another medicinal-chemistry paper using ipamorelin as the template for a new series of GH secretagogues, again chasing oral bioavailability by trimming size and hydrogen-bonding sites. Several analogues released GH potently in rat pituitary cells and in anaesthetised rats; the tetrapeptide NNC 26-0235 matched ipamorelin, GHRP-2, and GHRP-6 for injectable potency (ED50 ~2 nmol/kg in swine) and, like ipamorelin, raised basal GH more than 10-fold after oral dosing, though its oral bioavailability in dogs was modest (~10%). This is structure-activity research aimed at druggability, not an efficacy study of ipamorelin itself. For Ipamorelin, it is useful context on how the parent molecule seeded a family of derivatives. The endpoints are potency and bioavailability in animals and cells; these are preclinical findings, and human data would be needed before any clinical conclusion.
Plain-language abstract
Building on the peptide ipamorelin, this study created and tested a new series of related growth-hormone-releasing compounds, again with the goal of making versions that could be taken by mouth. The researchers made the molecules smaller and reduced certain chemical features that hinder gut absorption. Several of the new compounds triggered growth-hormone release strongly in rat pituitary-cell tests and in rats. One four-amino-acid compound, NNC 26-0235, matched ipamorelin and the peptides GHRP-2 and GHRP-6 for potency when injected into pigs, and, like ipamorelin, raised baseline growth hormone more than tenfold when given by mouth. However, only about 10% of an oral dose reached the bloodstream in dogs. A smaller three-part compound was better absorbed (about 20% in rats) but was not active in the body. The researchers concluded they had produced potent new growth-hormone-releasing compounds derived from ipamorelin. This is laboratory and animal research, not a study in humans.