AOD9604

AOD9604 (Advanced Obesity Drug 9604), also designated Tyr-hGH177-191, is a synthetic peptide fragment corresponding to the C-terminal lipolytic domain of human growth hormone (residues 177-191) with an additional N-terminal tyrosine residue. It was developed specifically to isolate and study the fat metabolism-promoting activities of growth hormone independently of the anabolic, IGF-1-elevating, and diabetogenic effects mediated through the classical GH receptor/JAK2/STAT5b signalling pathway that requires the N-terminal GH receptor-binding domain.

Human growth hormone (191 amino acids) produces multiple biological effects through two mechanistically separable domains. The N-terminal region (approximately residues 1-176) contains the primary GH receptor binding sites responsible for hepatic IGF-1 production, anabolic effects in muscle and bone, and anti-insulin metabolic actions. The C-terminal lipolytic domain (approximately residues 177-191) drives adipose tissue lipolysis through a mechanism that has been proposed to involve beta-3 adrenergic receptor (ADRB3) stimulation on adipocytes, independently of GHR signalling. AOD9604 consists of this isolated lipolytic domain, enabling research into adipose biology without confounding GHR-mediated anabolic and metabolic effects.

Published Phase 2 clinical research confirmed AOD9604's mechanistic specificity: administered to obese human volunteers, AOD9604 did not elevate serum IGF-1, did not affect fasting blood glucose or insulin sensitivity, and did not produce changes in blood pressure or heart rate attributable to beta-adrenergic stimulation — distinguishing it pharmacologically from both full-length GH and direct beta-adrenergic agonists. This clinical specificity provides a strong translational framework for interpreting laboratory research using AOD9604 in adipocyte models.

The primary in vitro research systems for AOD9604 are differentiated 3T3-L1 adipocytes (the standard murine adipocyte model) and primary adipocytes isolated from rodent epididymal, inguinal, or mesenteric fat depots. Key research endpoints include: glycerol release into conditioned medium (enzymatic colorimetric glycerol assay — each triglyceride hydrolysis event releases one glycerol, making it a stoichiometric measure of complete lipolytic events); non-esterified fatty acid (NEFA) release (colorimetric NEFA assay kits using acyl-CoA synthetase-based reactions); lipid droplet content and morphology (Oil Red O staining with optical density quantification or confocal imaging); and lipolytic enzyme activity including hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) phosphorylation by phospho-specific antibodies.

The comparative research toolkit for AOD9604 lipolysis research positions it against: isoproterenol (non-selective beta-1/2/3-adrenergic agonist — maximal lipolysis positive control); CL316,243 (selective ADRB3 agonist — pathway-specific positive control); full-length recombinant hGH (GHR agonist — complete GH biology positive control); and vehicle (negative control). Using selective ADRB3 antagonist SR59230A as a pre-treatment before AOD9604 allows determination of the ADRB3 dependence of any observed lipolytic activity.

Adipogenesis research using AOD9604 examines its effects on the differentiation programme: adding AOD9604 during the standard 3T3-L1 differentiation protocol (dexamethasone/IBMX/insulin induction) and measuring lipogenic gene expression (PPAR-gamma, C/EBPalpha, FABP4, SCD1), lipid accumulation by Oil Red O, and adiponectin secretion as markers of adipogenic differentiation extent.

MW: 1815.10 g/mol. CAS: 221231-10-3. Molecular formula: C78H123N23O23S2. Contains methionine — susceptible to oxidation under prolonged air exposure; prepare fresh solutions and store aliquots at -80°C. Reconstitute in bacteriostatic water at 1mg/mL. For laboratory and analytical research purposes only.

Comparative research toolkit: isoproterenol (non-selective beta-adrenergic agonist, maximal lipolysis positive control), CL316,243 (selective ADRB3 agonist), and full-length recombinant hGH (GHR agonist, complete GH biology control) provide the reference points for contextualising AOD9604's lipolytic specificity. Using selective ADRB3 antagonist SR59230A as pre-treatment before AOD9604 determines ADRB3 dependence of observed lipolytic activity. MW: 1815.10 g/mol. CAS: 221231-10-3. Contains methionine — prepare fresh solutions and store at -80°C to minimise oxidation. Reconstitute in bacteriostatic water at 1mg/mL. For laboratory and analytical research purposes only.