IGF-1 LR3 1mg

Compound Name: IGF1-LR3

Synonyms: LR3 IGF-1; Long Arg3 IGF-1; IGF-I [Nle3, Arg3, Long]

CAS Number: 946870-92-4

Molecular Formula: C₄₀₀H₆₂₅N₁₁₁O₁₁₅S₉

Molecular Weight: 9.1 kDa

Structure: Linear polypeptide

Peptide Sequence: Not available

Chemical Structure: No chemical structure available (per PubChem)

Mechanism of Action: IGF1-LR3 acts as a potent agonist of the IGF-1 receptor due to its structural similarity to endogenous IGF-1. The critical modifications—a 13-amino acid N-terminal extension and Arg substitution at the third residue—drastically lower its binding affinity for circulating IGFBPs, thereby increasing the proportion of free, receptor-accessible peptide. Upon binding to the IGF-1 receptor, IGF1-LR3 activates downstream PI3K/Akt and MAPK pathways, promoting protein synthesis, cell survival, proliferation, and differentiation. These effects underlie the compound’s pronounced anabolic and anti-catabolic properties seen in a range of experimental models, especially where IGF-1’s activity is otherwise neutralized by IGFBPs^1-4.

Biological Activity: IGF1-LR3 has robust in vivo and in vitro anabolic effects, including the reversal of dexamethasone-induced catabolic states, increased nitrogen retention, attenuation of muscle protein breakdown, and stimulation of cell survival and extracellular matrix production in vascular smooth muscle and other tissues. Its resistance to IGFBPs leads to 2-3 fold greater potency than native IGF-1 in stimulating weight gain, protein accrual, and tissue regeneration in experimental models. IGF1-LR3 also exhibits protective, anti-apoptotic, and matrix-stabilizing effects in models of vascular disease and tissue repair^1-4.

Storage: Store at -20°C or lower; protect from repeated freeze-thaw cycles.

Drug Categories: Experimental growth factor analog; IGF-1R agonist

Additional Notes:

• Not approved for clinical use in humans; for research purposes only.
• Designed for maximized selectivity to white adipose vasculature.

Summary Table:

Disclaimer: For Research Use Only. Not intended for human or veterinary use. This compound is supplied solely for laboratory and R&D purposes.

Detailed Product Description

IGF1-LR3 (Long R3 IGF-1) is a next-generation recombinant analog of human IGF-1, engineered to enhance biological activity through a 13-amino acid N-terminal extension and a specific residue substitution (arginine at position 3). These structural changes decrease the peptide’s affinity for IGF-binding proteins, increasing its half-life and functional bioavailability in the extracellular environment. As a result, IGF1-LR3 demonstrates superior potency over native IGF-1 in promoting protein synthesis, inhibiting muscle protein breakdown, and accelerating recovery from catabolic insults such as glucocorticoid exposure or tissue injury^1-3. Research shows that IGF1-LR3 effectively reverses dexamethasone-induced catabolism, restores nitrogen balance, and stimulates the synthesis and deposition of extracellular matrix proteins. Preclinical vascular models also reveal a pronounced stabilizing effect on smooth muscle cell survival and phenotype, even under highly inflammatory conditions. Due to these properties, IGF1-LR3 is a vital tool in metabolic, regenerative, and cardiovascular disease research, providing a unique means to dissect the physiological and pathological roles of IGF signaling independent of IGFBP-mediated sequestration^2-4.

Research Highlights

• Two to 3 fold increased efficacy over IGF-1 in reversing glucocorticoid-induced catabolism and muscle atrophy^1-2.
• Lower affinity for IGFBPs enables more IGF1-LR3 to be freely available for receptor binding and activation^1,3.
• Potently reduces muscle protein breakdown and increases nitrogen retention in catabolic models².
• Enhances smooth muscle cell survival, ECM production, and migration, protecting against apoptosis⁴.
• Demonstrates plaque-stabilizing and anti-inflammatory actions in vascular disease models².

Mechanism of Action

IGF-1 Receptor (IGF-1R) Agonism

• IGF1-LR3 binds to and activates IGF-1 receptors with high affinity, initiating key anabolic and anti-apoptotic signaling cascades, including PI3K/Akt and MAPK pathways¹.
• Stimulation of IGF-1R leads to increased protein synthesis, cell growth, and survival, as well as glucose uptake and metabolic regulation².
• The 13-amino acid N-terminal extension and Arg3 substitution sharply lower IGFBP binding, ensuring a greater proportion of IGF1-LR3 is available to bind and activate IGF-1R compared to native IGF-11^3,4.

IGFBP Insensitivity

• Reduced affinity for IGFBPs allows IGF1-LR3 to remain active in tissues with high IGFBP concentrations (e.g., during catabolic states), bypassing a major regulatory checkpoint that often limits the effects of native IGF-1^2-4.
• This increased bioavailability is associated with markedly greater anabolic and tissue restorative effects in vivo and in vitro¹.

Pharmacokinetic Profile

• Route of Administration: Subcutaneous injection (in animal models)
• Dosing Frequency: Effective as infusion or daily injection; continuous infusion is most potent
• Half-Life: Extended functional half-life in vivo due to resistance to IGFBPs

Formulation & Handling

• Lyophilized powder, reconstitute with sterile buffer (preferred Acetic Acid 0.6%)
• Protect from light, store at –20°C

Selected Clinical Trial Activity

IGF1-LR3 is a research-grade compound that has been studied in laboratory settings but has not undergone full clinical development. It is not approved for therapeutic use in humans, and no large-scale clinical trials have been conducted to evaluate its safety or efficacy as a medication. IGF1-LR3 is supplied strictly for laboratory research and investigational purposes only.

References

¹Tomas, F. M. et al. Insulin-like growth factor-I (IGF-I) and especially IGF-I variants are anabolic in dexamethasone-treated rats. Biochem. J. 282, 91–97 (1992).

²Von der Thüsen, J. H. et al. IGF-1 has plaque-stabilizing effects in atherosclerosis by altering vascular smooth muscle cell phenotype. Am. J. Pathol. 178, 924–934 (2011).

³Tomas, F. M. et al. Superior potency of infused IGF-I analogues which bind poorly to IGF-binding proteins is maintained when administered by injection. J. Endocrinol. 150, 77–84 (1996).

⁴Mohan, S. & Baylink, D. J. IGF-binding proteins are multifunctional and act via IGF-dependent and -independent mechanisms. J. Endocrinol. 175, 19–31 (2002).