New Oral Compound NN703 Potently Stimulates Growth Hormone Release

Growth hormone (GH) plays a crucial role in growth, metabolism, and body composition. Growth Hormone Deficiency (GHD) can lead to various health issues, including reduced muscle mass, increased fat, and impaired quality of life. Traditional GH replacement therapy often involves daily subcutaneous injections, which can be inconvenient and impact patient compliance. There is a significant need for effective, orally bioavailable compounds that can stimulate endogenous GH release, offering a more patient-friendly treatment option.

NN703 demonstrated high potency and selectivity for the GHS-R1a receptor in vitro, exhibiting a binding affinity (Ki) of 0.5 nM and an EC50 for calcium mobilization of 2.3 nM. In animal models, NN703 proved to be a highly effective oral GH secretagogue. Oral administration of NN703 at 1 mg/kg in rats resulted in a rapid and significant 5.2-fold increase in plasma GH levels compared to vehicle control, with peak levels observed at 60 minutes. > The most striking finding was that NN703 exhibited excellent oral bioavailability, estimated to be over 70% in both rat and dog models, a critical factor for an oral therapeutic. In beagle dogs, a lower dose of 0.3 mg/kg orally induced a robust 3.1-fold elevation in GH, maintaining elevated levels for up to 4 hours. Furthermore, NN703 showed a favorable pharmacokinetic profile with a half-life of approximately 2 hours in rats.