IGF-1 LR3

Overview

IGF-1 LR3 is an 83-amino-acid modified IGF-1 analog with a 13-residue N-terminal extension (MFPAMPLSSLFVN) and an Arg-3 substitution. These modifications reduce binding to IGF binding proteins (IGFBPs), extending effective half-life and increasing tissue bioavailability relative to native IGF-1. It is a research/cell-culture reagent and is NOT FDA-approved for any human use. Do not confuse with mecasermin (Increlex), which is recombinant human IGF-1 and IS FDA-approved for severe primary IGF-1 deficiency.

Mechanism of Action

IGF-1 LR3 binds the IGF-1 receptor (IGF-1R) with high affinity and drives PI3K/Akt and MAPK signaling, producing anabolic and mitogenic effects including muscle protein synthesis, satellite-cell activation, and broad cell proliferation. The Arg-3 substitution and N-terminal extension lower IGFBP affinity, so more free peptide reaches tissue receptors and the effective half-life is extended relative to native IGF-1 (which clears in minutes).

Research Summary

Francis et al. (J Mol Endocrinol, 1992) characterized the LR3 analog and showed its enhanced biological potency is driven by reduced IGFBP interaction, with lower activity in IGFBP-free systems. Tomas (Growth Horm IGF Res, 2001) infused LR(3)IGF-I in food-restricted rats and found it preserved body weight and nitrogen retention but did NOT conserve skeletal muscle protein, tempering simplistic 'potent muscle builder' claims from preclinical work alone. There are no controlled human trials supporting bodybuilding use. The IGF-1 axis is strongly implicated in breast, prostate, colorectal, and other cancers (Grimberg, Cancer Biol Ther, 2003), so chronic systemic exposure raises a genuine — not merely theoretical — tumorigenesis concern. IGF-1 and its analogs are prohibited at all times under the WADA Code (S2: Peptide Hormones, Growth Factors and Related Substances).

Dosing Information

Reported Side Effects

• Hypoglycemia (real risk — IGF-1 has insulin-like activity)
• Joint pain and arthralgia
• Acromegaly-like soft-tissue changes with prolonged high-dose use (jaw, hands, feet)
• Gut/visceral overgrowth reported with chronic supraphysiologic exposure
• Injection site irritation
• Unknown long-term tumorigenesis risk (IGF-1 pathway drives multiple cancers)

Research References

• Novel recombinant fusion protein analogues of insulin-like growth factor (IGF)-I indicate the relative importance of IGF-binding protein and receptor binding for enhanced biological potency (Francis et al., J Mol Endocrinol) (1992)
• Insulin-like growth factor-I (IGF-I) analogue, LR(3)IGF-I, ameliorates the loss of body weight but not of skeletal muscle during food restriction (Tomas, Growth Horm IGF Res) (2001)
• Mechanisms by which IGF-I May Promote Cancer (Grimberg, Cancer Biol Ther) — review of IGF-1 axis and tumorigenesis (2003)