Unregulated growth signaling at full strength
A long-acting IGF-1 analog with an N-terminal extension and Arg3 substitution.
Educational content. This page describes IGF-1 LR3 for informational purposes only and is not medical advice, diagnosis, or treatment. Consult a licensed provider before starting, stopping, or modifying any therapy.
Reduced plaque size and lumen stenosis while increasing smooth muscle cell content in an atherosclerotic mouse model, suggesting a potential vascular stabilizing effect.[8]
IGF-1 LR3 (Long R3 Insulin-Like Growth Factor-1) is an 83-amino-acid synthetic analog of human IGF-1, which is natively 70 amino acids. It incorporates two structural modifications: a 13-amino-acid extension at the N-terminus and a substitution of arginine for glutamic acid at position 3. These changes were engineered at the Cooperative Research Centre for Tissue Growth and Repair in Adelaide, Australia, primarily to create a more potent cell culture supplement for serum-free media, not as a human therapeutic.
The combined modifications reduce affinity for IGF binding proteins (IGFBPs) by over 1,000-fold. Since more than 99% of circulating native IGF-1 is normally sequestered by IGFBPs, this modification fundamentally changes the pharmacology: nearly all administered LR3 remains free and bioactive. The result is approximately 3-fold greater in vivo potency compared to native IGF-1. IGF-1 LR3 has never been studied in human clinical trials and is not approved for any medical use. It is banned by the World Anti-Doping Agency.
IGF-1 LR3 binds and activates the Type I IGF Receptor (IGF-1R), a transmembrane receptor tyrosine kinase. Upon binding, receptor autophosphorylation recruits IRS-1 (insulin receptor substrate-1), which activates two major downstream cascades.
The PI3K/Akt/mTOR pathway drives muscle protein synthesis through p70S6K and 4E-BP1 phosphorylation, inhibits muscle protein breakdown by suppressing atrogenes MuRF1 and atrogin-1 through FOXO transcription factor inactivation, enhances glucose uptake via GLUT4 translocation, and promotes cell survival by upregulating Bcl-2 and inhibiting BAD and caspase-9.
The MAPK/ERK pathway drives cellular proliferation through Ras-Raf-MEK-ERK1/2 signaling, promotes satellite cell activation and differentiation, and stimulates cell cycle progression through cyclin D1 expression. The critical difference from native IGF-1 is that LR3 bypasses the IGFBP regulatory system entirely, removing the body's natural brake on IGF-1 signaling intensity and duration.
Unregulated growth signaling at full strength
IGF-1 LR3 activates the IGF-1 receptor to drive PI3K/Akt/mTOR signaling (protein synthesis, anti-apoptosis, glucose uptake) and MAPK/ERK signaling (cell proliferation, satellite cell activation). Its over 1,000-fold reduction in IGFBP binding removes the natural regulatory brake on IGF-1 activity, producing approximately 3-fold greater potency and 20 to 30 hour bioavailability versus minutes for native IGF-1.
Key studies supporting the therapeutic use of this peptide.
LR3-IGF-1 and des(1-3) IGF-1 were 2.5 to 3 times more potent than native IGF-1 at restoring growth. However, neither fully replaced insulin-dependent metabolic processes in liver, muscle, and other tissues.
Tomas FM, Knowles SE, Owens PC, et al. — Biochem J, 294(Pt 3):725-729 (1993) · PubMed
LR3-IGF-1 increased tumor growth more than native IGF-1, even though it did not promote tumor growth in cell culture. It decreased carcass fat by 30% but failed to promote muscle protein accretion. Insulin co-administration had synergistic effects on host weight.
Tomas FM, Knowles SE, Owens PC, et al. — Biochem J, 291(Pt 3):781-787 (1993) · PubMed
Increased fractional weights of adrenals, gut, kidneys, and spleen but did not stimulate overall body growth, weight gain, or feed efficiency. Plasma IGF-1, IGF-2, and IGFBPs were all suppressed, indicating negative feedback on the endogenous GH/IGF axis.
Conlon MA, Tomas FM, Owens PC, et al. — J Endocrinol, 146(2):247-253 (1995) · PubMed
Decreased average daily gain, food intake, plasma IGFBP-3, IGF-1, insulin, and GH (23% mean reduction, 60% peak area reduction). Exogenous LR3-IGF-1 triggered negative feedback suppression that reduced overall growth rather than enhancing it.
Tomas FM, et al. — J Endocrinol, 155(2):377-385 (1997) · PubMed
Typical protocols used in clinical practice. Always consult a licensed provider for personalized dosing.
Subcutaneous/Intramuscular Infusion (Preclinical)
Subcutaneous/Intramuscular Infusion (Preclinical): All dosing data comes from animal studies. No human clinical trials exist.
There are zero human clinical trials of IGF-1 LR3. All dosing information comes exclusively from animal research, primarily in rats, guinea pigs, and pigs.
Animal studies produced mixed results: growth restoration in diabetic rats but growth inhibition in healthy pigs, likely from suppression of the endogenous GH/IGF axis through negative feedback.
The only FDA-approved IGF-1 product is mecasermin (Increlex), which uses unmodified recombinant human IGF-1 at carefully titrated doses of 40 to 120 mcg/kg twice daily for a narrow pediatric indication. LR3's bypass of IGFBP regulation makes it fundamentally different from this approved therapy.
IGF-1 LR3 was engineered as a cell culture reagent, not as a therapeutic. Its fundamental design principle of bypassing IGFBP regulation removes the body's natural controls on IGF-1 signaling, which is both its pharmacological advantage and its primary safety concern.
Direct evidence of tumor growth promotion exists: in rats bearing mammary tumors, LR3 increased tumor growth more than native IGF-1. Large epidemiological studies consistently associate elevated circulating IGF-1 with increased risk of breast, prostate, colorectal, thyroid, and kidney cancer.
Animal studies showed that exogenous LR3 can suppress the endogenous GH/IGF axis through negative feedback, paradoxically reducing rather than enhancing growth in healthy pigs. This suggests that the common assumption of dose-dependent benefit is incorrect.
See how IGF-1 LR3 compares to peptides with overlapping benefits.
| Peptide | Primary Use | Administration | Cycle Length | Key Differentiator |
|---|---|---|---|---|
| IGF-1 LR3 | Muscle Growth & Recovery | Injection | 4 to 7 days (animal studies only) | Over 1,000-fold reduction in IGFBP binding removes the natural regulatory brake on IGF-1 signaling, producing extended bioavailability but also eliminating safety controls |
| Tesamorelin | Body Composition & GHRH | Subcutaneous Injection | Ongoing daily | The only FDA-approved GHRH analog with Phase III data in over 800 patients, proven hepatoprotective effects, and physiologic pulsatile GH release |
| GHK-Cu | Anti-Aging & Recovery | Topical, Injection | 8–12 weeks | Only peptide demonstrated to modulate ~31% of human genes, epigenetically resetting cellular function toward a younger phenotype |
| Sermorelin | Anti-Aging & GH Restoration | Injection (daily) | 3–6 months | Only GHRH analog with FDA approval history and multi-decade safety record, uniquely preserving natural GH feedback |
| BPC-157 | Recovery & Healing | Injection, Oral | 4–8 weeks | Uniquely stable in gastric acid; broad multi-system healing with human IBD trial data |
Current FDA classification and compounding eligibility.
This substance does not appear on any FDA bulk drug substances list. It is classified as research-use only and cannot be legally compounded for human use.
IGF-1 LR3 does not appear on any FDA 503A or 503B bulk drug substances list. It is not FDA-approved for any human indication. While the FDA Substance Registration System has a UNII (M9L22Y19H9), this indicates only that the substance has been identified, not that it is approved or eligible for compounding. Significant risks include severe hypoglycemia and potential tumor growth acceleration. Available only as a research chemical.
Last verified April 12, 2026. PepHookup tracks public FDA actions. This is not legal or medical advice.
Francis GL, Ross M, Ballard FJ, et al. “Insulin-like growth factor (IGF)-II binding to IGF-binding proteins and IGF receptors is modified by deletion of the N-terminal hexapeptide or substitution of arginine for glutamate-3 in IGF-II.” J Mol Endocrinol, 8(1):R1-6 (1992)
Bryant KJ, Read LC, Forsberg G, Wallace JC “Design and characterisation of long-R3-insulin-like growth factor-I muteins which show resistance to pepsin digestion.” Growth Factors, 13(3-4):261-272 (1996)
Tomas FM, Knowles SE, Owens PC, et al. “Insulin-like growth factor-I and more potent variants restore growth of diabetic rats without inducing all characteristic insulin effects.” Biochem J, 294(Pt 3):725-729 (1993)
Tomas FM, Knowles SE, Owens PC, et al. “Effects of insulin and insulin-like growth factors on protein and energy metabolism in tumour-bearing rats.” Biochem J, 291(Pt 3):781-787 (1993)
Conlon MA, Tomas FM, Owens PC, et al. “Long R3 insulin-like growth factor-I (IGF-I) infusion stimulates organ growth but reduces plasma IGF-I, IGF-II and IGF binding protein concentrations in the guinea pig.” J Endocrinol, 146(2):247-253 (1995)
Tomas FM, et al. “Short-term infusion of Long R3 IGF-I in finisher pigs.” J Endocrinol, 155(2):377-385 (1997)
Voorhamme D, Yandell CA “LONG R3IGF-I as a more potent alternative to insulin in serum-free culture of HEK293 cells.” Mol Biotechnol, 34(2):201-204 (2006)
von der Thusen JH, et al. “IGF-1 has plaque-stabilizing effects in atherosclerosis by altering vascular smooth muscle cell phenotype.” Am J Pathol, 178(2):924-934 (2011)
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