Peptigrade

Metabolic & Body Composition

Fragment 176-191

Human growth hormone C-terminal fragment 176-191 (hGH 176-191) — sequence FLRIVQCRSVEGSCGF·Also known as: HGH Fragment 176-191, hGH 176-191, Lipolytic fragment, Somatotropin (176-191), Frag 176-191

FDARegulatory status

Not approved for human use in any indication. Fragment 176-191 is sold legally in the United States only as a research chemical for in-vitro and animal work. Its tyrosine-N-terminal analog AOD-9604 reached Phase 2b for obesity (Metabolic Pharmaceuticals, sponsor program wound down after the 2007 Phase 2b readout) and was later granted U.S. GRAS Self-Affirmed status in 2014 as a food-ingredient adjunct — neither pathway is an FDA drug approval, and neither applies to unmodified Fragment 176-191.

WADARegulatory status

Captured by the 2026 WADA Prohibited List under S2.2 (peptide hormones, growth factors, related substances, and mimetics) — growth hormone fragments and GH-releasing peptides are prohibited at all times, in and out of competition.

Regulatory note ·No registered clinical trial of unmodified Fragment 176-191 has been completed in humans. All published human data reside on the AOD-9604 analog (Tyr-hGH 177-191), principally the Metabolic Pharmaceuticals Phase 2a (Ng, 12-week, n~300) and Phase 2b (Stier-era, 24-week, n~534) obesity trials, neither of which showed a clinically meaningful placebo-adjusted weight-loss signal — the program did not advance to Phase 3. Fragment 176-191 itself has not been characterized in humans for PK, immunogenicity, or long-term safety. It is not a pharmaceutical product in any major jurisdiction.

§ The quick take

TL;DR · Editor’s summary

Fragment 176-191 is the unmodified parent peptide of AOD-9604 — the 16-residue C-terminal fragment of human growth hormone (FLRIVQCRSVEGSCGF) originally characterized at Monash University in the 1990s as the region that retains hGH's lipolytic effect without engaging the growth-hormone receptor. It is the same molecular family as AOD-9604 but has not itself been taken into human clinical trials in any registered program. Every piece of human efficacy and safety data attributed to it in the gray market is actually data from the AOD-9604 analog (Tyr-hGH 177-191), and the AOD-9604 program failed: the Metabolic Pharmaceuticals 24-week Phase 2b obesity trial did not produce a clinically meaningful placebo-adjusted weight loss, the obesity program was not advanced to Phase 3, and the molecule was later repositioned out of the prescription pipeline.

Preclinically, the mechanism is characterized in mice: Heffernan 2001 (Endocrinology, PMID 11713213) showed reduced body weight gain and increased fat oxidation in obese mice, no effect in lean mice, no response in β3-AR knockout mice, and no hyperglycemic or IGF-1-raising effects — consistent with an indirect mechanism that upregulates β3-adrenergic receptor expression on adipocytes and activates hormone-sensitive lipase via a DAG/PKC pathway. Under the Peptigrade rubric, the top grade is D: the mechanism is partially understood, there are no RCTs of the unmodified fragment in humans, the analog that was tested failed to beat placebo, and long-term human safety and PK data are absent. It is not FDA-approved and is WADA-prohibited at all times under S2.

If the lipolytic mechanism is the feature of interest, the AOD-9604 page is the correct reference for what the human evidence actually says — and it says less than marketers claim.

§ Grade matrix

The grade
per outcome.

One peptide can earn very different grades for different uses. Here is every outcome we’ve graded for Fragment 176-191, sorted by strength of evidence.

D

Fat loss & body-weight reduction

Weak

Parent compound for AOD-9604. Zero RCTs of unmodified Fragment 176-191 in humans. The AOD-9604 analog — the only form with human efficacy data — failed to beat placebo on clinically meaningful weight loss in the 24-week Phase 2b trial, and the program was not advanced. Animal evidence (Heffernan 2001, Ng 2001) shows weight loss in obese mice but not lean mice, and only via a β3-AR–dependent indirect mechanism.

6 studiesUpdated 2026-04-20
D

Adipocyte lipolysis (free fatty acid release)

Weak

In-vitro evidence in isolated rat adipocytes (Heffernan 2001 companion work) shows stimulation of glycerol release via DAG → PKC → HSL phosphorylation. No confirmed human adipose-tissue lipolysis measurements for the unmodified fragment. Mechanism is indirect (β3-AR upregulation) rather than direct receptor agonism.

4 studiesUpdated 2026-04-20
D

β3-adrenergic receptor upregulation

Weak

Heffernan 2001 showed increased β3-AR mRNA in obese-mouse adipose tissue after chronic AOD-9604 treatment, and β3-AR knockout mice lost responsiveness — a mechanistic finding, not a clinical outcome. No human tissue data.

3 studiesUpdated 2026-04-20
C

Metabolic selectivity (no IGF-1 / glucose effect)

Mixed

Consistent preclinical and AOD-9604 human trial evidence that the C-terminal fragment does not raise IGF-1, does not impair glucose tolerance, and does not reproduce the hyperglycemic side-effect profile of full-length hGH. This is a negative/selectivity finding, not an efficacy claim — graded higher only because the absence of those effects is well-replicated.

5 studiesUpdated 2026-04-20
D

Cartilage / osteoarthritis (articular cartilage regeneration)

Weak

An exploratory AOD-9604 arm in Phase 2 osteoarthritis work (Phosphagenics/Lateral Pharma era) did not produce a positive regulatory package. No Fragment 176-191-specific human cartilage data exists. Mechanism is not obviously lipolytic and is not well-characterized.

2 studiesUpdated 2026-04-20
Ins.

Long-term body-composition maintenance

Insufficient

No published human data on unmodified Fragment 176-191 extending beyond a single dose. AOD-9604 was studied out to 24 weeks in Phase 2b without a sustained placebo-adjusted effect. No maintenance-phase data in humans.

0 studiesUpdated 2026-04-20

§ Why this grade

Sub-scores for this outcome.

Fat loss & body-weight reduction

Every grade rolls up six weighted sub-scores, each rated 1 to 5 with a written justification. Here is how the top-outcome grade was constructed.

Mechanism understood

3 / 5

β3-AR indirect mechanism is the best-characterized pathway (Heffernan 2001, knockout validation). Downstream DAG → PKC → HSL is plausible but the specific upstream receptor engagement remains unidentified. No human PK. Graded above the animal-only floor because the negative findings (no GHR binding, no IGF-1 effect, no hyperglycemia) are also mechanistically coherent.

Human studies (count + quality)

1 / 5

Zero RCTs of unmodified Fragment 176-191 in humans. Cross-applying the AOD-9604 Phase 2a (Ng, 12-week) and Phase 2b (24-week, n~534) data to the unmodified fragment is not the same as having the fragment tested — and even that cross-applied dataset did not beat placebo on clinically meaningful weight loss.

Effect vs placebo

1 / 5

For the unmodified fragment there is no placebo-controlled human measurement. For the AOD-9604 analog, the Phase 2b readout did not produce a clinically meaningful placebo-adjusted weight-loss signal — the obesity program was not advanced. Animal-vs-sham in obese mice does not clear the placebo bar.

Long-term safety data

1 / 5

No published human exposure of unmodified Fragment 176-191 beyond single doses. The 24-week AOD-9604 Phase 2b is the longest human exposure in the family and is not directly the same molecule.

Side effect profile

3 / 5

Preclinical toxicology and the AOD-9604 Phase 2 program did not surface serious adverse events, hyperglycemia, or IGF-1 elevation. This is a clean preclinical and small-human safety record — but a clean pilot-scale record is not a safety database, and immunogenicity / repeat-dose tolerability for the unmodified fragment is uncharacterized.

Regulatory status

1 / 5

Not FDA-approved in any indication. WADA-prohibited at all times under S2.2 (peptide hormones, growth factors, related substances, and mimetics) on the 2026 Prohibited List. Sold in the U.S. only as a research chemical. The AOD-9604 analog's 2014 Self-Affirmed GRAS status is a food-ingredient classification, not an FDA drug approval, and does not extend to the unmodified fragment.

§ What the science says

How Fragment 176-191
works.

Plain-English explanation of the molecule and its proposed mechanism, written at an 8th-grade reading level so anyone can engage with it. Every claim is linked to a primary source below.

What it is

Fragment 176-191 is a synthetic 16-amino-acid peptide (sequence FLRIVQCRSVEGSCGF, MW 1,799.1 Da, CAS 66004-57-7, PubChem CID 16131230) corresponding to residues 176–191 of the 191-amino-acid human growth hormone molecule. The two cysteines at positions 182 and 189 form an intramolecular disulfide bond that gives the fragment a cyclic C-terminal structure. It was originally identified by Ng, Heffernan, and colleagues at Monash University as the minimal C-terminal region of hGH that retains fat-mobilizing activity while losing the GH-receptor binding that drives IGF-1 production, hyperglycemia, and anabolism. Its closely related tyrosine-N-terminal analog, AOD-9604 (Tyr-hGH 177-191), is the form that advanced into human obesity trials; unmodified Fragment 176-191 has not been run through a registered clinical program.

How it works

  1. 01

    What it is not — no growth hormone receptor engagement

    The primary GH-receptor-binding epitopes of full-length hGH sit in the N-terminal and middle regions of the molecule (approximately residues 1–134). Fragment 176-191 lacks those domains, so it does not measurably bind the GH receptor and does not stimulate hepatic IGF-1 production, does not drive GHR-dependent protein synthesis, and does not reproduce the hyperglycemic / insulin-resistance signature of exogenous hGH (Heffernan 2001, Endocrinology). This receptor-independence is the peptide's defining feature and the reason it is studied at all.

  2. 02

    β3-adrenergic receptor upregulation in adipose tissue

    The best-characterized mechanism is indirect. Heffernan 2001 (PMID 11713213) demonstrated that chronic treatment of obese mice with AOD-9604 (the tyrosine analog of Fragment 176-191) increased β3-adrenergic receptor (ADRB3) mRNA expression in adipose tissue, restoring receptor density toward lean-mouse levels. In the same study, β3-AR knockout mice showed no weight-loss or lipolytic response to either hGH or AOD-9604, establishing that β3-AR is necessary for the effect. The fragment itself does not appear to directly bind or activate β3-AR; it increases the pool of available receptors so endogenous catecholamines produce a larger lipolytic signal.

  3. 03

    DAG → PKC → hormone-sensitive lipase in isolated adipocytes

    In vitro work in isolated rat adipocytes (Heffernan 2001 and the companion 177-191 adipocyte study from the same group) traced the downstream signal: the peptide triggers a biphasic release of diacylglycerol (DAG), DAG activates protein kinase C (PKC), and PKC phosphorylates hormone-sensitive lipase (HSL) — the rate-limiting enzyme of triglyceride hydrolysis. The fragment also modestly inhibits lipoprotein lipase (LPL), limiting new triglyceride uptake. The specific upstream receptor coupling to DAG has not been identified in peer-reviewed literature.

  4. 04

    Obesity-dependent responsiveness

    Heffernan 2001 and Ng 2001 (Int J Obesity) both reported that only obese mice, not lean mice, showed body-weight reduction and increased fat oxidation in response to the fragment. The working explanation is that obesity downregulates adipose β3-AR expression, and the fragment's mechanism corrects that suppression rather than driving lipolysis in an already-normal system. Whether this obesity-dependence translates to humans has not been tested because there are no human Fragment 176-191 trials.

  5. 05

    What is NOT known about the mechanism

    No specific high-affinity receptor for Fragment 176-191 has been identified. The plasma half-life is reported as roughly 30 minutes based on animal work, but human PK data for the unmodified fragment are absent from peer-reviewed literature. Whether repeated dosing triggers anti-drug antibodies, whether route of administration changes tissue distribution, and whether the in-vitro adipocyte signaling reproduces in human adipose tissue in vivo are all open questions. The McGuire-style theoretical cancer-biology concerns that attach to growth-factor-family peptides have not been systematically evaluated for Fragment 176-191.

§ Investigated uses

What it’s
been studied for.

Investigated does not mean proven. This list shows every use that appears in the published literature, regardless of evidence strength. See the grade matrix above for which ones have actually held up.

  • Body-weight reduction in diet-induced and genetic obesity (mouse)

    Heffernan 2001 (AOD-9604 analog) and Ng 2001; consistent effect in obese mice, no effect in lean mice

  • Fat oxidation / energy expenditure (mouse)

    Ng 2001 (Int J Obesity) documented increased fat oxidation with chronic fragment treatment

  • β3-AR pathway characterization

    Heffernan 2001 β3-AR knockout study established mechanism-dependence on β3-AR

  • Isolated adipocyte lipolysis (rat)

    In vitro evidence of HSL activation via DAG/PKC in the Heffernan 2001 companion adipocyte work

  • Obesity in humans

    No registered trial of unmodified Fragment 176-191. The AOD-9604 analog ran Phase 2a (Ng, 12-week) and Phase 2b (24-week, n~534) and did not produce a clinically meaningful placebo-adjusted weight-loss signal; program did not advance to Phase 3

  • Osteoarthritis / articular cartilage (preliminary)

    Exploratory AOD-9604 arms explored in the mid-2010s (Phosphagenics / Lateral Pharma era); no positive regulatory package

  • Historical hGH C-terminal fragment structure-activity

    1978 PubMed report (PMID 645904) on hyperglycemic and other activities of synthetic C-terminal hGH fragments — foundational SAR work identifying 176-191 as the active core

§ The honest gaps

What we don’t
know yet.

Every peptide page on this site is required to include this section. Absence of evidence is information. If we don’t flag the gaps, we’re lying by omission.

  • !

    No randomized controlled trial of unmodified Fragment 176-191 has been conducted in humans for any indication. Every human efficacy or safety claim in the gray market is cross-applied from AOD-9604 — and that cross-application assumes equivalence that has never been formally demonstrated.

  • !

    Human pharmacokinetics are undocumented in peer-reviewed literature for the unmodified fragment. The ~30-minute plasma half-life reported by marketers is from rodent work. Bioavailability by subcutaneous and (reported) oral routes has not been characterized in humans.

  • !

    The identity of the upstream receptor coupling Fragment 176-191 to DAG/PKC signaling is not established. Mechanism is inferred from downstream pathway activation.

  • !

    The AOD-9604 Phase 2b failure to beat placebo on clinically meaningful weight loss has never been explained at a mechanism level. Whether this reflects species translation failure, dose, route, patient-selection, or a true ceiling on the β3-AR-indirect mechanism in humans is unknown — and applies directly to the unmodified fragment too.

  • !

    Long-term (>6 month) human safety data does not exist for the unmodified fragment. The 24-week AOD-9604 exposure is the longest human dataset in the family.

  • !

    Immunogenicity and anti-drug antibody formation have not been characterized for repeated Fragment 176-191 dosing in humans.

  • !

    The obesity-specificity observed in mice (only obese animals respond) has not been tested in humans.

  • !

    Interaction with other GH-axis peptides (sermorelin, CJC-1295, ipamorelin, MK-677) is unstudied despite being a common stacking pattern in the gray market.

§ On YouTube

What experts and
influencers say.

We index YouTube content discussing Fragment 176-191and tag every speaker by credential and trust level. The goal is not to summarize the internet — it’s to tell you which voices to weight.

  • Fragment 176-191 vs AOD-9604 — what the human trials actually show

    Dr. Kyle Gillett·MD, Family Medicine

    Makes the correct distinction between the unmodified fragment (no human trials) and AOD-9604 (Phase 2b that missed on weight loss). Cautions against cross-applying AOD-9604 claims to the unmodified research-chemical fragment.

    Verified credentials

  • The Fat-Loss Peptide Market — Why Fragment 176-191 and AOD-9604 Underperformed

    Peter Attia Drive (guest)·MD, internal medicine / longevity

    Discusses the GH-axis rationale and why the AOD-9604 Phase 2b obesity readout did not advance to Phase 3 — relevant context for anyone evaluating the parent fragment.

    Verified credentials

  • I Tried Fragment 176-191 for 8 Weeks — Fat Loss Results

    Anonymous fitness influencer·Unverified

    Anecdotal claim with no objective measurement, no control, and no acknowledgment that the compound has no human RCT. Representative of the overstated-benefit pattern common to this category. Do not weight against published evidence.

    Caution — anecdotal

§ Citations

Every claim,
linked to source.

All 9 sources informing this page, with DOI or PubMed identifiers. Click through to the primary literature.

  1. [01]

    The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and beta(3)-AR knock-out mice

    Heffernan M, Summers RJ, Thorburn A, Ogru E, Gianello R, Jiang WJ, Ng FM · Endocrinology · 2001

    AnimalPMID 11713213
  2. [02]

    Hyperglycemic action of synthetic C-terminal fragments of human growth hormone

    Ng FM, Bornstein J · Am J Physiol · 1978

    AnimalPMID 645904
  3. [03]

    Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment

    Ng FM, Sun J, Sharma L, Libinaki R, Jiang WJ, Gianello R · Int J Obesity · 2000

    AnimalDOI
  4. [04]

    Somatotropin (176-191) — PubChem CID 16131230 (structure, formula, CAS 66004-57-7)

    U.S. National Library of Medicine · PubChem · 2026

    RegulatoryLink
  5. [05]

    WADA 2026 Prohibited List (in force January 1, 2026) — Section S2 Peptide Hormones, Growth Factors, Related Substances and Mimetics

    World Anti-Doping Agency · WADA · 2026

    RegulatoryLink
  6. [06]

    FDA 503A Bulk Drug Substances Categories — April 15, 2026 Update (growth hormone fragments not on the approved Category 1 list)

    U.S. Food and Drug Administration · FDA · 2026

    RegulatoryLink
  7. [07]

    Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone — Monash University research archive

    Heffernan M (dissertation) / Monash University · Monash University · 2001

    AnimalLink
  8. [08]

    The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and beta(3)-AR knock-out mice — Semantic Scholar record

    Heffernan M, Summers RJ, Thorburn A, et al. · Semantic Scholar · 2001

    AnimalLink
  9. [09]

    AOD-9604 Self-Affirmed GRAS determination (2014) — food-ingredient classification for the tyrosine analog (not a drug approval, does not apply to unmodified Fragment 176-191)

    Calzada International / Phosphagenics · Industry regulatory filing · 2014

    RegulatoryLink

§ Adjacent peptides

Worth reading
alongside this.

Compare

AOD-9604

The tyrosine-N-terminal analog of Fragment 176-191 and the only form of this peptide with published human clinical trial data. Anyone researching Fragment 176-191 should read the AOD-9604 page — the Phase 2a and Phase 2b obesity data there are what the gray market misapplies to the unmodified fragment.

Read its grades

Compare

IGF-1

The hepatic growth factor that full-length hGH drives through the GH receptor. Fragment 176-191's defining selectivity feature is that it does NOT raise IGF-1 — the IGF-1 page is the reference for what the peptide is deliberately leaving on the table.

Read its grades

Compare

Sermorelin

GHRH analog that raises endogenous hGH (and therefore IGF-1 and lipolytic activity together). Sits at the opposite end of the GH-axis design space from Fragment 176-191 — Sermorelin recruits the full hormone, Fragment 176-191 isolates one subfunction.

Read its grades

Where to research further

Looking for Fragment 176-191
for laboratory research?

Peptigrade does not sell peptides. RiboCore is one supplier we track that publishes batch-level certificates of analysis (mass spec, HPLC purity) for research-grade material. We have no commercial relationship with them — listing here is editorial.

For research use only · Not for human consumption · Verify legality in your jurisdiction

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