IGF-1 LR3 (Long R3) Growth Factor - 1mg

IGF-1 LR3 Peptide

IGF-1 LR3 (Insulin-like Growth Factor-1 Long R3) is a synthetic peptide analog of human IGF-1 engineered for enhanced stability and activity in research settings. This lengthened variant differs from native IGF-1 by an arginine substitution at the third amino acid and a 13-amino-acid extension on its N-terminus. These modifications greatly increase IGF-1 LR3’s half-life and reduce its affinity for IGF binding proteins, resulting in higher bioavailability and potency than regular IGF-1. In experimental models, IGF-1 LR3 exhibits powerful anabolic effects—it stimulates cell growth and proliferation—making it a valuable tool for investigating muscle development, metabolic pathways, and neuroregeneration in in vitro and in vivo studies.

Overview

Mechanism of Action: IGF-1 LR3 is an agonist of the IGF-1 receptor (IGF1R), mimicking the action of endogenous IGF-1 with amplified efficacy. Upon binding to IGF1R on cell surfaces, it activates intracellular signaling cascades such as the PI3K/Akt/mTOR and MAPK pathways. Activation of these pathways drives protein synthesis and cell-survival programs, while promoting cell-cycle progression. In skeletal muscle tissue, IGF-1 signaling through Akt increases muscle protein synthesis and inhibits protein degradation, yielding net anabolic effects. Notably, IGF-1 LR3’s poor binding to IGF-binding proteins means more of the peptide remains free to interact with receptors, enhancing its potency. Studies in animal models have shown IGF-1 LR3 to be significantly more potent than IGF-1; for example, in catabolic rat models IGF-1 LR3 produced 2–3× greater anabolic response than IGF-1 in terms of weight gain and nitrogen retention. This superior activity is attributed to its sustained receptor activation and improved metabolic stability.

Muscle Growth and Regeneration

A primary research interest for IGF-1 LR3 is skeletal muscle hypertrophy and repair. IGF-1 is well-established as a key growth factor in muscle development—it stimulates proliferation of muscle satellite cells (muscle stem cells) and their differentiation into myoblasts. In injured or atrophying muscle, IGF-1 levels rise to activate satellite cells and promote regeneration of muscle fibers. By activating IGF1R, IGF-1 LR3 potently amplifies these processes: it has been shown to induce greater protein synthesis and myotube formation in muscle cell cultures. In vivo, IGF-1 analogs like LR3 enhance muscle fiber size and number by increasing muscle protein synthesis and reducing proteolysis, even under catabolic conditions. Research suggests IGF-1 LR3 can counteract muscle wasting in models of glucocorticoid-induced atrophy and muscular dystrophy by preserving muscle mass. Its activation of satellite cells and anabolic signaling pathways contributes to accelerated muscle repair following injury. Unlike growth hormone that works indirectly, IGF-1 LR3 directly targets muscle tissue; for example, experiments have shown IGF-1’s direct action via PI3K/Akt to induce myotube hypertrophy without needing cell proliferation. These findings underscore IGF-1 LR3’s utility in studying muscle growth mechanisms and potential therapeutic approaches for sarcopenia or cachexia.

Insulin-Like Metabolic Pathways

As a close analog of IGF-1 (which shares ~50% structural homology with insulin), IGF-1 LR3 engages metabolic pathways similar to insulin’s. It can bind insulin receptors at high concentrations and especially acts through hybrid insulin/IGF-1 receptors. Consequently, IGF-1 LR3 enhances glucose uptake and nutrient transport into cells, supporting tissue growth and recovery. IGF-1 in general has been shown to improve insulin sensitivity and reduce blood glucose levels in both animals and humans. Clinical research demonstrated that administering IGF-1 to diabetic patients lowered blood sugar and reduced required insulin doses; however, IGF-1’s insulin-like hypoglycemic effect is much milder than insulin’s. In research use, IGF-1 LR3’s metabolic effects are of interest for studying diabetes, muscle metabolism, and fat reduction. By facilitating uptake of glucose, amino acids, and fatty acids into muscle, IGF-1 LR3 creates a pro-anabolic, nutrient-rich environment that favors lean tissue growth over fat accumulation. Notably, its prolonged half-life allows these metabolic and anabolic effects to persist over a day, unlike native IGF-1 which is cleared from circulation within minutes to hours. Researchers leverage this property to examine sustained IGF-1 signaling on metabolic tissues and its interactions with insulin and growth hormone in energy homeostasis.

Neuroprotective Effects

Beyond muscle and metabolism, IGF-1 LR3 is being explored for its neurotrophic and neuroprotective properties. IGF-1 is produced in the central nervous system and plays vital roles in brain development, neuronal growth, and synaptic plasticity. It can influence brain function and has been reported to promote neurite outgrowth, support myelination, and inhibit neuronal apoptosis. These actions are largely attributed to IGF-1’s activation of PI3K/Akt signaling in neurons and glia, which turns on anti-apoptotic and anti-inflammatory pathways. Research indicates that IGF-1 can protect neurons against excitotoxic injury and oxidative stress, and low IGF-1 activity is associated with neurodegenerative conditions. In experimental settings, IGF-1 LR3 has shown promise in models of nerve damage by improving motor-neuron survival and functional recovery, presumably by reducing cell death and fostering regeneration. Ongoing studies are examining IGF-1 LR3 in contexts like Alzheimer’s disease, stroke, and peripheral nerve repair, where IGF-1’s ability to activate pro-survival signaling in neurons could slow degeneration or enhance regeneration. Its prolonged action offers a potential advantage in maintaining neurotrophic support.

Chemical Makeup

Molecular Formula: C₄₀₀H₆₂₅N₁₁₁O₁₁₅S₉

Molecular Weight: 9,117.5 g/mol

Other Names: Long R3 IGF-1; Long Arg³ Insulin-like Growth Factor-1; LR3IGF-I; IGF-I Long R3

CAS Number: 143045-27-6

Research and Clinical Studies

IGF-1 LR3 and IGF-binding proteins

IGF-1 analogs designed to bind poorly to IGF-binding proteins have shown greater potency than native IGF-1 when administered by injection in experimental models.

Receptor signaling

Canonical IGF-1 receptor activation engages PI3K/Akt and MAPK cascades that regulate cell growth, protein synthesis, and survival.

Skeletal muscle

IGF-1 has been studied for roles in myogenesis, where it supports satellite-cell activation, proliferation, and differentiation, and contributes to muscle maintenance and repair.

Neuroprotection

IGF-1 has been reported to protect neurons via PI3K/Akt–dependent mechanisms in a variety of injury and stress models.

Metabolic effects

IGF-1 exhibits insulin-like activity on carbohydrate and protein metabolism and has been investigated, including as an IGF-1/IGFBP-3 complex, for effects on insulin requirements and glucose handling in research settings.

IGF-1 LR3 peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering.

References

1. Tomas FM, Lemmey AB, Read LC, Ballard FJ. Superior potency of infused IGF-I analogues which bind poorly to IGF-binding proteins is maintained when administered by injection. J Endocrinol. 1996;150(1):77–84. https://pubmed.ncbi.nlm.nih.gov/8708565/
   
2. MilliporeSigma. LONG R3 IGF-I, human (I1271) Product Information Sheet. Describes Arg³ substitution and 13-aa N-terminal extension used to reduce IGFBP binding. https://www.sigmaaldrich.com/deepweb/assets/sigmaaldrich/product/documents/159/144/i1271pis.pdf
   
3. The signaling landscape of insulin-like growth factor 1. J Biol Chem. Review of IGF-1 receptor pathways including PI3K-AKT and MAPK. https://www.jbc.org/article/S0021-9258%2824%2902549-3/fulltext
   
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   Role of IGF-1 in skeletal muscle mass maintenance. Trends Endocrinol Metab. Review on myogenesis and satellite-cell biology. https://www.cell.com/trends/endocrinology-metabolism/fulltext/S1043-2760%2809%2900090-3
   
5. Implications of Insulin-Like Growth Factor-1 in Skeletal Muscle and Various Diseases. Cells. Overview of IGF-1 in muscle proliferation and repair. https://www.mdpi.com/2073-4409/9/8/1773
   
6. IGF-1 via PI3K/AKT/S6K signaling pathway protects dorsal-root-ganglion neurons under high glucose. Open Life Sciences. https://www.degruyterbrill.com/document/doi/10.1515/biol-2019-0056/html
   
7. IGF-1 signaling via PI3K/AKT confers neuroprotection in retinal models. J Mol Neurosci. https://link.springer.com/article/10.1007/s12031-014-0448-7
   
8. Insulin-Like Growth Factor I Has a Direct Effect on Glucose and Protein Metabolism in Type 1 Diabetes. J Clin Endocrinol Metab. https://academic.oup.com/jcem/article/89/1/425/2840653
   
9. Effects of recombinant human IGF-I/IGFBP-3 complex on glucose and lipid metabolism in type 1 diabetes. Diabetes. https://diabetesjournals.org/diabetes/article/55/8/2365/12356/Effects-of-Recombinant-Human-IGF-I-IGF-Binding
   
10. Combination of IGF-I and IGFBP-3 in adolescents and adults with type 1 diabetes. J Clin Endocrinol Metab. https://academic.oup.com/jcem/article/85/4/1518/2852802
    
11. Insulin-like growth factor-1 deficiency and metabolic syndrome. J Transl Med. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-015-0762-z
    
12. PI3K-AKT-mTOR pathway overview. My Cancer Genome knowledgebase. https://www.mycancergenome.org/content/pathways/PI3K-AKT1-MTOR/