IGF-1 LR3

IGF-1 LR3 (Long-Arg3 IGF-1) is a synthetic 83-amino-acid analog of human insulin-like growth factor 1. It contains the native human IGF-1 sequence extended by 13 amino acids at the N-terminus and an arginine substitution at position 3 that dramatically reduces its affinity for IGF-binding proteins (IGFBPs). The result is a longer-acting, more bioavailable IGF-1 analog used as a research tool in cell-culture and animal-model studies of growth and tissue repair.

Peppudex card: see the mechanism + evidence-grade summary at [Peppudex / IGF-1 LR3](https://peppudex.com/peptides/igf-1-lr3).

Overview

Native IGF-1 is rapidly bound by IGFBPs in circulation, reducing its free fraction and biological half-life to roughly 10-12 minutes. IGF-1 LR3 was engineered to circumvent this binding · its arginine substitution at position 3 reduces IGFBP affinity by approximately 1000-fold, extending the functional half-life to approximately 20-30 hours in research models.

Mechanism

IGF-1 LR3 binds the IGF-1 receptor (IGF-1R) with similar affinity to native IGF-1, triggering the same PI3K/Akt and Ras/MAPK cascades that drive cell growth, proliferation, and inhibition of apoptosis. The N-terminal extension and Arg3 substitution do not alter receptor engagement; they only affect binding-protein interactions in circulation.

See: IGF-1, Growth_hormone_receptor.

Evidence

IGF-1 LR3 is widely used as a research reagent in cell-culture growth-factor studies. The compound is also a published doping agent for athletes seeking growth and recovery effects without the cost of full-length recombinant IGF-1.

Preclinical animal studies have used IGF-1 LR3 to model the effects of supra-physiological IGF-1 signaling on muscle hypertrophy, bone healing, and neuronal survival. No completed Phase 3 human clinical trials are registered for IGF-1 LR3 itself; native IGF-1 (mecasermin, Increlex) is FDA-approved for severe primary IGF-1 deficiency in children.

Dosing literature

Animal research has used subcutaneous doses of 20-50 µg/kg/day. The wiki does not recommend any human dose; IGF-1 LR3 is research-use only.

Pharmacokinetics

IGF-1 LR3 has a plasma half-life of approximately 20 to 30 hours, roughly 70 times longer than native IGF-1 (~10 to 12 minutes). The extension comes from a 13-amino-acid N-terminal addition plus an Arg3 substitution that reduces binding to all six IGFBPs (insulin-like growth factor binding proteins), leaving the molecule in free circulation. The free-IGF-1 state is the basis for both the prolonged activity and the elevated hypoglycemia risk vs native IGF-1.

Storage

Lyophilized IGF-1 LR3 is stable at –20 °C for at least 24 months. Once reconstituted with bacteriostatic water (or 0.6% acetic acid for some sources), store at 2-8 °C and use within 14-21 days. Reconstituted IGF-1 LR3 is less stable than typical peptides and benefits from short reconstitution cycles.

Regulatory status

• United States. Research-use only. Not FDA-approved.
• WADA. IGF-1 analogs are prohibited at all times under S2 (peptide hormones, growth factors, related substances) on the [WADA Prohibited List](https://www.wada-ama.org/en/prohibited-list).

Side effects (from animal + community-reported literature)

• Hypoglycemia (the dominant safety concern; free unbound IGF-1 activity drives glucose uptake)
• Class-based concern around tissue hypertrophy with chronic use, including cardiac hypertrophy
• Theoretical neoplasm-progression concern given IGF-1's role in cell proliferation pathways (no controlled human data)
• Reported headaches, joint stiffness, and water retention in community-reported user reports
• WADA-prohibited at all times under category S2 (peptide hormones, growth factors)

See also

• IGF-1 · native ligand
• Growth_hormone · upstream regulator
• Tesamorelin · upstream GHRH analog that increases endogenous IGF-1
• Reconstitution · vial-prep math
• [Peppudex card · IGF-1 LR3](https://peppudex.com/peptides/igf-1-lr3) · mechanism, evidence grades A-F, FAQs, peer-reviewed sources

References

• Francis GL, et al. "Insulin-like growth factor (IGF)-I and IGF-binding protein in tissue extracts and culture media." Endocrinology. 1992;130(4):2275-83. PMID 1372243.
• Tomas FM, et al. "Long-Arg3 IGF-I has higher anabolic potency than insulin or IGF-I in vivo in the rat." Endocrinology. 1993;132(4):1727-32. PMID 8462469.