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Human-limitedFat-targeting hGH fragment for metabolic support

AOD9604

Also indexed as Advanced Obesity Drug 9604, hGH Fragment 176-191, AOD-9604

AOD9604 is a synthetic peptide fragment derived from the C-terminal region of human growth hormone (amino acids 176–191), developed originally by Monash University as an anti-obesity drug. It mimics the lipolytic (fat-burning) effects of growth hormone without stimulating IGF-1 production or promoting cell proliferation. Research suggests it stimulates fat breakdown and inhibits fat formation, with a favorable safety profile compared to full-length hGH.

Overview

Following subcutaneous administration, AOD9604 reaches peak plasma concentration within approximately 15–30 minutes, with rapid clearance (half-life <1 hour) due to its small size and lack of PEGylation or albumin-binding modifications. Despite the short half-life, downstream activation of HSL and suppression of lipogenesis persist beyond plasma clearance through second-messenger amplification. Bioavailability via subcutaneous injection is estimated at 60–80% based on analogy with similarly-sized peptide fragments; oral bioavailability in trials was investigated but found insufficient due to proteolytic degradation.

Proposed mechanism

AOD9604 binds to beta-adrenergic receptors and activates lipolysis by stimulating the breakdown of triglycerides in adipocytes, while simultaneously inhibiting lipogenesis (the conversion of non-fat foods into fat). Unlike full-length growth hormone, it does not activate the GH receptor in a way that drives IGF-1 secretion or anabolic tissue growth, making it metabolically selective. Preclinical data also suggest it may support cartilage and bone repair through mechanisms involving TGF-beta signaling.

What the evidence supports

Human data exists but the trials are small, short-term, or not yet replicated.

Graded Human-limited

Human data that exists but is thin: open-label work, single-arm studies, small cohorts, or observational follow-up without randomisation.

Key citations

Representative primary sources, including results that did not favour the compound.

  1. [1]

    Metabolic effects of the C-terminal fragment of human growth hormone in obese mice and humans

    · Journal of Endocrinology 168(3): 535–543 · 2001

  2. [2]

    AOD9604: A lipolytic fragment of human growth hormone with a 12-week phase II clinical trial

    · Regulatory Toxicology and Pharmacology 46(2): 142–150, Elsevier · 2006

  3. [3]

    Chondroprotective and chondrogenic effects of AOD9604 in a murine model of osteoarthritis

    · Osteoarthritis and Cartilage (Centenon/Metabolic Pharmaceuticals preclinical data) · 2012

Citation records in this build are illustrative placeholders for the design.

Reference information for research purposes. Not medical advice, and not a recommendation to use any compound. Many entries describe substances that are not approved for human use.

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