Study wrapper · #224
Pharmacological characterisation of a new oral GH secretagogue, NN703.
Editor's note
This is a preclinical characterisation of NN703, an orally active GH secretagogue derived from ipamorelin, with ipamorelin and GHRP-6 as comparators. Across rat pituitary cells, receptor-binding assays, swine, and dogs, NN703 stimulated GH release with potency similar to GHRP-6, worked through the GHS (not GHRH) receptor, showed about 30% oral bioavailability and a ~4-hour half-life in dogs, and increased 14-day body-weight gain in rats. An interesting wrinkle: its receptor-binding and signalling potencies were lower than its GH-releasing potency predicted, hinting the pharmacology is not fully explained by simple GHS-R1a occupancy. For Ipamorelin, the relevance is contextual, since NN703 was the orally bioavailable follow-on to the injectable parent. This is entirely animal and in-vitro work on a related compound; it speaks to druggability, not to any human effect. Human data would be needed before clinical conclusions.
Plain-language abstract
This report describes NN703, a new growth-hormone-releasing compound designed to be taken by mouth and derived from the peptide ipamorelin. In lab dishes of rat pituitary cells, NN703 triggered growth-hormone release about as strongly as the known peptide GHRP-6, and this action was blocked by drugs that block the growth-hormone-secretagogue receptor, but not by a blocker of the separate GHRH pathway, showing it works through the same receptor family as ipamorelin and GHRP-6. In pigs it raised growth hormone specifically, with only a modest cortisol rise. In dogs, giving it by mouth raised growth hormone in a dose-dependent way, with about 30% of an oral dose reaching the bloodstream and a blood half-life of about 4 hours. In rats, 14 days of daily oral dosing significantly increased body-weight gain versus untreated animals. The researchers concluded NN703 is an orally active, growth-hormone-specific secretagogue. All of this is laboratory and animal work; it does not show effects in people.