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AOD-9604 vs IGF-1 LR3

AOD-9604 and IGF-1 LR3 are studied in overlapping research areas, which is why they are frequently compared. This is a neutral side-by-side reference drawn from published preclinical literature and laboratory handling data.

Shared research areas:Metabolic
Class16-residue hGH C-terminal fragment analogue with one intramolecular disulfideRecombinant 83-residue protein analogue of IGF-1
Molecular weight1815.1 g/molNot specified
CAS number221231-10-3Not assigned / not specified
Purity spec≥99%≥99%
Research areasMetabolicHormonal & Endocrine, Metabolic, Musculoskeletal
Primary diluentBacteriostatic water (0.9% benzyl alcohol)Dilute acetic acid (0.1 M) or 10 mM HCl — required for initial dissolution
Working windowCommonly worked with for 2-3 weeks at 2-8 °C in bacteriostatic water.Short: commonly worked with within 1–2 weeks at 2–8 °C, or frozen in single-use aliquots.
Lead degradation routeDisulfide exchange (scrambling) and formation of disulfide-linked dimers, accelerated above about pH 8.Denaturation and aggregation — the dominant failure mode, and one that has no equivalent in short unstructured peptides.
Freeze–thawAliquot on first reconstitution and freeze aliquots once; repeated cycles concentrate peptide at the ice interface and favour intermolecular disulfide pairing.Single-use aliquots are the standard practice, and here it genuinely matters. IGF-1 LR3 has tertiary structure to lose — unlike the unstructured short peptides in this catalogue, it can denature, and denaturation is not reversible on rewarming.
Light sensitivityNo specific light requirement beyond normal practice.No specific light requirement beyond normal practice.

How they actually differ

Comparing the two: AOD-9604 is 16-residue hgh c-terminal fragment analogue with one intramolecular disulfide, while IGF-1 LR3 is recombinant 83-residue protein analogue of igf-1 — different molecular classes with different handling consequences; they call for different primary diluents (bacteriostatic water (0.9% benzyl alcohol) versus dilute acetic acid (0.1 m) or 10 mm hcl — required for initial dissolution); their leading degradation routes differ (disulfide exchange (scrambling) and formation of disulfide-linked dimers, accelerated above about ph 8. for AOD-9604, denaturation and aggregation for IGF-1 LR3), so the storage precautions that matter are not the same; their practical working windows differ once reconstituted. The sections below set out each in full.

AOD-9604 — origin

AOD-9604 is residues 177-191 of human growth hormone with an extra tyrosine added at the N-terminus (Tyr-Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser-Cys-Gly-Phe), closed by a disulfide between the two cysteines. It came out of Frank Ng's group at Monash University in Australia and was developed by Metabolic Pharmaceuticals in Melbourne as an obesity candidate. That programme was discontinued in 2007 after a 24-week phase 2b trial did not show a clinically meaningful outcome, and the compound never reached approval as a medicine.

IGF-1 LR3 — origin

IGF-1 LR3 is an engineered analogue carrying two changes to native IGF-1: an arginine substitution at position 3 and a 13-residue N-terminal extension. The Arg3 substitution is the functional one — it drastically reduces binding to IGF binding proteins, which normally sequester the great majority of circulating IGF-1. The result is a molecule that stays free rather than bound.

AOD-9604 research themes

Lipid metabolism in obese and β3-AR knockout mice

Heffernan et al. (Endocrinology 2001) compared hGH and AOD9604 over 14 days in obese mice and in β3-adrenergic-receptor knockout mice. Both raised the repressed β3-AR expression in obese mice, but neither changed body weight or lipolysis in the knockout mice over the long-term protocol, leading the authors to conclude the lipolytic actions were not mediated directly through β3-AR.

Insulin sensitivity in obese Zucker rats

Ng et al. (Horm Res 2000) studied oral administration of AOD9604 in obese Zucker rats, reporting reduced body-weight gain and increased adipose lipolytic activity, and — unlike intact hGH — no impairment of insulin sensitivity on euglycaemic clamp.

Human safety and tolerability data

Stier et al. (J Endocrinol Metab 2013) pooled six randomised, double-blind, placebo-controlled trials and reported no change in serum IGF-1, no adverse effect on carbohydrate metabolism, and no anti-AOD9604 antibodies in tested participants. The same development programme did not show a clinically meaningful weight outcome.

Cartilage in a rabbit osteoarthritis model

Kwon and Park (Ann Clin Lab Sci 2015) gave intra-articular AOD9604, with or without hyaluronic acid, in a collagenase-induced knee osteoarthritis model in rabbits and scored cartilage morphology, histology and lameness.

IGF-1 LR3 research themes

IGFBP evasion

The Arg3 substitution reduces binding-protein affinity, which is the entire design rationale.

Cell proliferation

Widely used in cell-culture research as a growth-factor supplement.

Satellite cell activation

Studied in muscle-biology research models.

PI3K/Akt signalling

The canonical downstream pathway examined in IGF-1 receptor research.

AOD-9604 handling

  • Let the vial reach room temperature before opening.
  • Add diluent gently down the vial wall and swirl; do not vortex.
  • Keep reducing agents (DTT, TCEP, β-mercaptoethanol) and alkaline buffers away from the stock.
  • Label aliquots with reconstitution date and diluent.

IGF-1 LR3 handling

  • Dissolve in dilute acetic acid or dilute HCl FIRST; do not attempt direct dissolution in water or PBS.
  • Add carrier protein (e.g. 0.1% BSA) for storage of dilute solutions to prevent adsorptive loss.
  • Prepare single-use aliquots — freeze–thaw denaturation is irreversible.
  • Do not vortex; agitation denatures folded proteins at the air–liquid interface.

Both third-party tested

Every Popular Peptides batch of AOD-9604 and IGF-1 LR3 is independently tested by HPLC and LC-MS with a published Certificate of Analysis. Enter a lot number to pull the COA for a specific vial.

AOD-9604 reference

IGF-1 LR3 reference

Related comparisons

AOD-9604 and IGF-1 LR3 are supplied strictly as research chemicals for in-vitro laboratory and research use only. They are not intended for human or animal consumption, diagnostic, or therapeutic use. This comparison summarizes published preclinical literature and laboratory handling data; it is not medical advice, not a claim of efficacy, and not usage guidance.