Scientists Discover Novel Orally Active Growth Hormone Secretagogues
Background
Growth hormone secretagogues (GHSs) are compounds that stimulate the release of growth hormone, which has various therapeutic applications, including potential treatments for growth hormone deficiency or sarcopenia. However, many potent GHSs, like the lead compound ipamorelin, often lack sufficient oral bioavailability, limiting their practical use and requiring inconvenient injectable administration. This study aimed to develop novel GHSs with improved oral activity and reduced molecular size.
Results
The study successfully identified a novel class of growth hormone secretagogues (GHSs) with improved oral properties. Most of the tested compounds demonstrated an oral bioavailability (fpo) in dogs ranging from 10% to 55%, indicating significant absorption. The most potent compound exhibited an in vivo ED50 of 30 nmol/kg body weight in swine after intravenous dosing, demonstrating high efficacy. This potency was achieved while simultaneously reducing the molecular weight to between 500 and 650 Da compared to the lead compound ipamorelin, suggesting a successful optimization strategy. The rational design approach proved effective in maintaining or improving potency while enhancing drug-like properties.
Why It Matters
The discovery of these novel, orally active growth hormone secretagogues represents a significant advancement in the field of endocrinology and drug development. Oral administration offers a more convenient and patient-friendly alternative to injections, potentially expanding the therapeutic applications of growth hormone-releasing compounds. This research lays foundational work for developing new oral therapies for conditions benefiting from growth hormone modulation, such as growth hormone deficiency, muscle wasting, or age-related decline. Future steps would involve further preclinical optimization, safety profiling, and eventually human clinical trials.