Insulin-like Growth Factor-1 Long R3 (IGF-1 LR3) is a synthetic, 83-amino acid analog of human IGF-1, a critical hormone involved in growth and development. It was developed through recombinant DNA technology to address the limitations of native IGF-1, which has a very short half-life in circulation due to its high affinity for binding proteins. The ‘Long R3’ designation refers to its two key modifications: an amino-terminal 13-amino acid extension peptide and the substitution of arginine for glutamic acid at position 3. These alterations significantly reduce its affinity for IGF-binding proteins (IGFBPs), particularly IGFBP-3, which is the primary carrier in serum. This results in a peptide with a substantially extended half-life and increased bioavailability compared to the native hormone, making it a potent and persistent research tool for studying IGF-1-mediated pathways in vitro and in vivo. Its significance lies in its utility for probing the anabolic, mitogenic, and metabolic effects of the IGF-1 axis without the confounding rapid clearance of the endogenous form, offering clearer insights into tissue growth, repair, and cellular proliferation mechanisms.
Quick Facts
| Also Known As | IGF-1 LR3, Long R3 IGF-1, IGF-1 Long R3, Long Arg3 IGF-1 |
|---|---|
| Sequence | MFPAMPLSSLFVNGPRTPLPQHPPDYSYSFGANRRPYKTELKRAQCRPSDLRRLEMYCAPLKPAKSA |
| Molecular Formula | C400H600N100O120S6 (approximate, based on sequence) |
| Molecular Weight | 9100 Da (approximate) |
Research Parameters
| Half-Life | ~20-30 hours (in research models, significantly longer than native IGF-1) |
|---|---|
| Stability | Lyophilized powder is stable for at least 24 months when stored at -20°C, protected from light and moisture. After reconstitution in bacteriostatic water or sterile acetic acid solution, it should be stored at 2-8°C and is typically stable for 7-14 days, though specific stability data can vary. |
| Solubility | Bacteriostatic Water (0.9% benzyl alcohol) or sterile 0.1M Acetic Acid. The acetic acid solution is often preferred to prevent adsorption to surfaces. |
| Vial Size | 1 mg |
| Storage (Lyophilized) | -20°C, protected from light and moisture |
| Storage (Reconstituted) | 2-8°C (refrigerated), for a limited period (e.g., 7-14 days) |
| Typical Research Dose | 10-200 mcg/kg (in animal research models) |
| Cycle Parameters | Daily subcutaneous injection, with study durations ranging from days to several weeks in preclinical research protocols. |
| Amino Acid Count | 67 |
Mechanism of Action
IGF-1 LR3 functions primarily by activating the Insulin-like Growth Factor-1 Receptor (IGF-1R), mimicking the action of endogenous IGF-1 but with prolonged activity due to its reduced binding to inhibitory proteins. Upon binding, it initiates a cascade of intracellular signaling events.
IGF-1R Activation and Dimerization: IGF-1 LR3 binds to the extracellular α-subunits of the IGF-1R, inducing conformational changes that lead to receptor dimerization and autophosphorylation of tyrosine residues on the intracellular β-subunits.
PI3K/Akt Pathway: The phosphorylated IGF-1R recruits and phosphorylates Insulin Receptor Substrate (IRS) proteins. These adaptor proteins then activate Phosphoinositide 3-kinase (PI3K), which converts PIP2 to PIP3. PIP3 recruits Akt (Protein Kinase B) to the membrane, where it is phosphorylated and activated. Activated Akt promotes protein synthesis via mTOR, inhibits apoptosis, and stimulates glucose uptake, driving anabolic growth and cell survival.
MAPK/ERK Pathway: Simultaneously, the activated IGF-1R/IRS complex can recruit Grb2/SOS, activating the small GTPase Ras. This initiates the MAPK cascade (Raf, MEK, ERK). Phosphorylated ERK translocates to the nucleus, where it activates transcription factors like Elk-1, leading to the expression of genes involved in cell cycle progression and proliferation.
Reduced IGFBP Binding: The core mechanistic distinction of IGF-1 LR3 is its dramatically lowered affinity for IGF-binding proteins, especially IGFBP-3. In serum, over 95% of endogenous IGF-1 is bound in a ternary complex with IGFBP-3 and an acid-labile subunit (ALS), which sequesters it and limits its receptor access. IGF-1 LR3 evades this sequestration, resulting in a higher concentration of 'free', receptor-active peptide and a significantly extended functional half-life.
Research Applications
Muscle and Skeletal Tissue: Research indicates IGF-1 LR3 promotes hypertrophy and hyperplasia of skeletal muscle cells. It stimulates satellite cell activation and fusion, increases protein synthesis rates, and may aid in the recovery of muscle tissue from injury or atrophy in model systems, highlighting its role in anabolic processes.
Bone and Cartilage: Studies demonstrate that IGF-1 LR3 supports osteoblast proliferation and activity, enhancing bone matrix formation and mineralization. In cartilage research, it exhibits chondroprotective and anabolic effects, promoting the synthesis of collagen and proteoglycans, which is relevant for investigating osteoarthritis and connective tissue repair.
Metabolic Studies: IGF-1 LR3 has been shown to influence glucose metabolism by enhancing insulin sensitivity and promoting glucose uptake in muscle and adipose tissue models. This makes it a compound of interest for research into metabolic disorders and the interplay between the IGF-1 and insulin signaling pathways.
Wound Healing and Skin: In dermal fibroblast and animal wound models, IGF-1 LR3 accelerates the healing process. It stimulates fibroblast proliferation, collagen deposition, and re-epithelialization, providing a research tool for investigating cutaneous regeneration and scar formation.
Safety & Side Effects
Data on the safety profile of IGF-1 LR3 is derived from animal studies. Potential side effects observed or theorized based on the mechanism of IGF-1 signaling include hypoglycemia due to its insulin-like activity, organomegaly (enlargement of organs like the kidneys, spleen, or heart) with chronic, high-dose exposure, and potential exacerbation or promotion of pre-existing neoplasms due to its potent mitogenic properties. Anecdotal reports from non-clinical contexts sometimes mention local injection site reactions, headaches, or joint discomfort, but these are not systematically documented in the scientific literature. Theoretical concerns also exist regarding acromegaly-like symptoms and altered lipid profiles with prolonged, supraphysiological exposure.
Dosage Information
Disclaimer: The following information is derived solely from published preclinical research studies and is presented for educational purposes only. It does not constitute dosing recommendations for humans.
In animal research models (typically rodents), IGF-1 LR3 is commonly administered via subcutaneous injection. Reported dose ranges vary widely depending on the study objective and species, but often fall between 10 mcg/kg and 200 mcg/kg of body weight per day. Some in vitro studies use concentrations in the nanomolar (nM) range. Administration is typically daily, and research protocols may last from several days to multiple weeks to observe chronic effects.
References
Francis, G.L., Ross, M., Ballard, F.J., Milner, S.J., Senn, C., McNeil, K.A., Wallace, J.C., King, R., Wells, J.R.E. 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. Journal of Molecular Endocrinology, 1992.
Ballard, F.J., Francis, G.L., Ross, M., Bagley, C.J., May, B., Wallace, J.C. Engineered analogues of insulin-like growth factor (IGF)-I with altered binding properties for IGF-binding proteins and the type 1 IGF receptor. Molecular and Cellular Endocrinology, 1993.
Barton, E.R., Morris, L., Musaro, A., Rosenthal, N., Sweeney, H.L. Muscle-specific expression of insulin-like growth factor I counters muscle decline in mdx mice. Journal of Cell Biology, 2002.
Philippou, A., Halapas, A., Maridaki, M., Koutsilieris, M. Type I insulin-like growth factor receptor signaling in skeletal muscle regeneration and hypertrophy. Journal of Musculoskeletal & Neuronal Interactions, 2007.
Clemmons, D.R. Role of IGF-I in skeletal muscle mass maintenance. Trends in Endocrinology & Metabolism, 2009.
Yakar, S., Leroith, D., Brodt, P. The role of the growth hormone/insulin-like growth factor axis in tumor growth and progression: Lessons from animal models. Cytokine & Growth Factor Reviews, 2005.
Jones, J.I., Clemmons, D.R. Insulin-like growth factors and their binding proteins: biological actions. Endocrine Reviews, 1995.