HGH Fragment 191-203

HGH Fragment 191-203 (Tyr-Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser; molecular weight 1495.78) is a 13-residue C-terminal fragment of human growth hormone (residues 191 through 203 of the mature 191-residue hGH polypeptide) developed as a research tool for separating the lipolytic activity of growth hormone from the somatogenic (growth-promoting) and insulinotropic activities. The full-length 191-residue hGH produces both lipolytic effects (acute fatty acid mobilization, chronic reduction of fat mass with a delay) and somatogenic and insulin-like effects (longitudinal bone growth in pediatric populations, insulin resistance in chronic exposure). Carboxypeptidase digestion of hGH produces fragments that retain selective subsets of these activities; the 191-203 fragment was characterized in the 1990s as a lipolytic-selective fragment in rodent adipocyte models and at the obese rodent in vivo level. The shorter fragment AOD9604 (KDC-MN; aod-9604), a tyrosine-conjugated 16-residue C-terminal fragment, was developed by Metabolic Pharmaceuticals (now Lateral) as a clinical agent in the same activity class and reached Phase 2 in obesity before discontinuation owing to insufficient effect size. Fragment 191-203 is the simpler underlying research tool from which AOD9604 was derived. The principal pharmacological signature is direct activation of beta-3 adrenergic receptor or downstream lipolytic signaling at the adipocyte level (the precise mechanism remains debated), increased fatty acid oxidation, and reduced de novo lipogenesis, without engagement of the GH receptor and without IGF-1 elevation. Plasma half-life is short (minutes) and the compound is administered subcutaneously. The compound is not approved by any regulatory authority and is sold only as a research-grade peptide; the principal published evidence base is from the 1990s and early 2000s and the clinical translation through AOD9604 did not produce a marketed agent.