IGF-1 LR3 1mg

IGF-1 LR3 (Long Arg3 Insulin-like Growth Factor 1) is an 83-amino-acid recombinant analog of human insulin-like growth factor 1 (IGF-1) with two structural modifications: an arginine substitution at position 3 of the native IGF-1 sequence, and a 13-amino-acid N-terminal extension. These modifications were specifically engineered to dramatically reduce binding to IGF-binding proteins (IGFBPs) — the carrier proteins that normally bind and inactivate the majority of circulating IGF-1 in human plasma. The result is a more potent and longer-acting IGF-1 analog widely used in cell culture research, where IGFBP interference is a known confounder, and in animal model research examining IGF-1 axis biology. Native IGF-1 is FDA-approved as mecasermin (Increlex) for severe primary IGF-1 deficiency in pediatric patients.

It is sold for laboratory and analytical research only and is not approved by the U.S. Food and Drug Administration as a therapeutic drug for any indication.

Molecular Structure and Stability

IGF-1 LR3 is an 83-amino-acid single-chain polypeptide with three intramolecular disulfide bonds maintaining its tertiary structure. Its molecular weight is approximately 9,117 Daltons. The two key structural modifications relative to native human IGF-1 are: (1) substitution of glutamic acid with arginine at position 3, which dramatically reduces IGFBP binding affinity, and (2) an N-terminal extension of 13 amino acids derived from methionyl porcine growth hormone, which further reduces IGFBP binding and extends biological activity in research applications.

The combined effect of these modifications is a research compound with substantially reduced IGFBP binding compared to native IGF-1 — published research has documented IGFBP affinity reductions of 10-fold or greater. In cell culture systems where IGFBPs in serum or media compete with cell-surface IGF-1 receptors for binding, this reduced IGFBP binding makes IGF-1 LR3 substantially more potent than native IGF-1 at activating IGF-1 receptor signaling. The extended half-life in biological systems (approximately 20–30 hours in some research models versus 12–15 minutes for native IGF-1) makes it the preferred research tool for sustained IGF-1 receptor activation studies.

The lyophilized (freeze-dried) form supplied for research is stable at -20°C for up to 24 months when sealed and protected from moisture. Following reconstitution with bacteriostatic water, the compound retains research-grade integrity for approximately 30 days when refrigerated at 2–8°C and protected from light. Repeated freeze-thaw cycles should be avoided.

Mechanism of Action — IGF-1 Receptor Signaling in Human Biology

IGF-1 LR3 activates the IGF-1 receptor (IGF-1R), the same receptor activated by native human IGF-1. The IGF-1R is a transmembrane receptor tyrosine kinase expressed across virtually all human tissues, where it mediates anabolic, growth-promoting, and survival signaling.

IGF-1R activation and downstream signaling. Receptor activation triggers two principal intracellular signaling cascades — the PI3K/Akt pathway (driving cell growth, protein synthesis, and survival) and the Ras/MAPK pathway (driving cell proliferation and differentiation). Both pathways are central to human cellular biology and dysregulated in multiple disease contexts.

Muscle protein synthesis. Research has documented IGF-1's role in skeletal muscle protein synthesis through PI3K/Akt/mTOR pathway activation. This pathway is foundational to skeletal muscle hypertrophy in human physiology and is the same axis activated by leucine, mechanical loading, and insulin in muscle research contexts.

Cell proliferation and survival. IGF-1 signaling drives cell cycle progression and inhibits apoptosis across multiple human cell types. This anti-apoptotic function is particularly relevant to research in tissue repair, neuronal survival, and developmental biology — and is a recognized factor in oncology research, where IGF-1R signaling is dysregulated in multiple cancer types.

Glucose metabolism. Despite the receptor name, IGF-1R has structural and functional overlap with the insulin receptor. IGF-1 LR3 has been studied for its effects on glucose uptake and insulin sensitivity in human and animal research models, with relevance to metabolic and diabetes research.

Bone and cartilage biology. IGF-1 is the principal mediator of growth hormone's effects on bone and cartilage growth in human development. IGF-1 axis dysfunction is implicated in growth disorders, and research using IGF-1 LR3 in cell culture has examined chondrocyte and osteoblast biology.

Neuronal biology. IGF-1R is widely expressed in human nervous tissue, where it mediates neuronal survival, neurogenesis, and synaptic plasticity. Research has examined IGF-1 axis biology in the context of neurodegenerative diseases including Alzheimer's and ALS.

Human Clinical Context — Native IGF-1 and Mecasermin

Native human IGF-1 has been pharmaceutically developed as mecasermin (Increlex), an FDA-approved recombinant human IGF-1 indicated for severe primary IGF-1 deficiency in pediatric patients. Mecasermin's clinical use provides validated human pharmacological data on IGF-1 receptor activation effects, including documented effects on linear growth, body composition, glucose metabolism, and other endpoints. Mecasermin and IGF-1 LR3 are distinct compounds — mecasermin is the native IGF-1 sequence used clinically; IGF-1 LR3 is the modified research analog with reduced IGFBP binding.

Research informed by the mecasermin clinical experience and broader IGF-1 axis research includes:

Growth disorder research. Severe primary IGF-1 deficiency, Laron syndrome, and IGF-1 receptor disorders provide human disease contexts validating IGF-1's central role in growth biology. Research using IGF-1 LR3 in cell culture and animal models extends mechanistic understanding of these conditions.

Sarcopenia and muscle research. Age-related skeletal muscle loss (sarcopenia) is associated with declining IGF-1 axis activity in elderly humans. Research in muscle cell biology has used IGF-1 LR3 extensively as a tool to study IGF-1R-mediated anabolic signaling.

Tendon and connective tissue research. Tendon fibroblasts and chondrocytes express IGF-1R. Research into tendon repair biology has examined IGF-1 axis activation as a mechanism for accelerating the slow tendon healing observed in aging and diabetic populations.

Neurodegenerative disease research. IGF-1 and IGF-1R have been studied in Alzheimer's, ALS, and other neurodegenerative conditions where neuronal survival pathways are dysregulated. Research has examined whether IGF-1 axis activation could provide neuroprotective effects in human disease contexts.

Cancer research context. IGF-1R signaling is dysregulated in many cancer types and is itself a therapeutic target. Research has examined IGF-1 signaling in tumor biology — generally with a goal of inhibiting rather than activating the pathway in cancer contexts. This represents an important counterpoint in IGF-1 axis research and a reason researchers exercise particular care with IGF-1 compounds in protocols that could intersect with oncology questions.

Quality Verification — What Our COA Documents

Every batch of IGF-1 LR3 supplied by Elara is independently analyzed by a third-party laboratory before release. Our Certificate of Analysis documents two distinct verification measures:

HPLC purity (≥99%). High-performance liquid chromatography separates the recombinant peptide from synthesis-related impurities, truncation products, and misfolded variants. Our specification requires a minimum 99% purity at the main peak. IGF-1 LR3 contains three disulfide bonds that must form correctly during folding, making purity verification particularly important — misfolded variants with incorrect disulfide connectivity have substantially different biological activity.

Mass spectrometry identity confirmation. MS analysis confirms that the molecular weight of the peak compound matches the theoretical molecular weight of IGF-1 LR3 (~9,117 Da), verifying both structural identity and the presence of the N-terminal extension and Arg3 modification distinguishing it from native IGF-1.

The COA accompanies every shipment and is also available for download on this product page.

Reconstitution and Handling for Research

For laboratory research applications, IGF-1 LR3 is typically reconstituted using bacteriostatic water (0.9% benzyl alcohol). For some cell culture applications, researchers may use other diluents (such as 0.1% BSA in dilute acetic acid) consistent with their experimental protocols. Standard practice involves slow addition of solvent along the inside wall of the vial — never directly onto the lyophilized powder, which can cause aggregation. The vial is then gently swirled (not shaken or vortexed) until the peptide is fully dissolved.

Once reconstituted, the solution should be stored at 2–8°C, protected from light, and used within 30 days for optimal molecular integrity. For longer-term storage of reconstituted aliquots, researchers commonly aliquot and freeze at -80°C to avoid repeated freeze-thaw cycles. Sterile technique is essential during all handling steps. Researchers performing in vitro work or animal model studies should refer to their institution's IACUC protocols and cell culture handling guidelines specific to their experimental design.

Frequently Asked Questions

What is IGF-1 LR3?
IGF-1 LR3 is an 83-amino-acid recombinant analog of human insulin-like growth factor 1 with two structural modifications: an arginine substitution at position 3 (the "R3" in the name) and a 13-amino-acid N-terminal extension (the "Long" in the name). These modifications dramatically reduce IGFBP binding, making the compound substantially more potent than native IGF-1 in research systems where IGFBPs would otherwise sequester active compound.

How is IGF-1 LR3 different from mecasermin (Increlex)?
Mecasermin is recombinant native human IGF-1, FDA-approved for severe primary IGF-1 deficiency in pediatric patients. IGF-1 LR3 is a modified research analog with reduced IGFBP binding and extended biological activity. The two compounds are pharmacologically distinct — mecasermin is used in clinical pediatric endocrinology; IGF-1 LR3 is used in research applications, particularly cell culture work where IGFBP interference would otherwise complicate experimental interpretation.

How is IGF-1 LR3 different from IGF-1 DES?
IGF-1 DES (also called des(1-3)IGF-1) is another modified IGF-1 analog with the first three amino acids removed, also reducing IGFBP binding but through a different mechanism. IGF-1 LR3 has the N-terminal extension plus Arg3 substitution, while IGF-1 DES has N-terminal truncation. Both compounds are used in research; LR3 is more commonly cited in published literature.

Why does IGF-1 LR3 have reduced IGFBP binding?
The arginine at position 3 disrupts the IGFBP binding interface, and the N-terminal extension provides additional steric interference with IGFBP binding. The combined effect is approximately 10-fold or greater reduction in IGFBP affinity compared to native IGF-1. In cell culture systems, this means more of the compound is available to bind IGF-1 receptors rather than being sequestered by IGFBPs in serum or media.

Has IGF-1 LR3 been studied in humans?
IGF-1 LR3 itself has limited direct human clinical research — most of its use has been in cell culture and animal model research. The pharmacology of IGF-1 receptor activation has been extensively studied in humans through native IGF-1 (mecasermin) clinical experience. The pharmacological understanding from native IGF-1 clinical use informs interpretation of IGF-1 LR3 research findings, while acknowledging that the modified compound has different IGFBP interactions.

What does HPLC ≥99% purity actually mean for IGF-1 LR3?
High-performance liquid chromatography is the analytical standard for assessing protein purity. A specification of ≥99% indicates that, of all UV-detectable species in the analyzed sample, at least 99% of the integrated peak area corresponds to the target compound. For IGF-1 LR3 specifically, the three disulfide bonds must form correctly — misfolded variants with incorrect disulfide connectivity would register as separate species and reduce the purity specification.

How long is IGF-1 LR3 stable after reconstitution?
Reconstituted IGF-1 LR3 retains research-grade integrity for approximately 30 days when stored refrigerated at 2–8°C and protected from light. For longer-term storage, researchers commonly aliquot and freeze at -80°C. Lyophilized (unreconstituted) IGF-1 LR3 is stable at -20°C for up to 24 months when properly sealed.

What human pathways does IGF-1 LR3 research target?
The most-studied pathways with direct human clinical relevance include IGF-1 receptor signaling (PI3K/Akt and Ras/MAPK cascades), skeletal muscle protein synthesis (mTOR pathway), bone and cartilage biology, neuronal survival and neurogenesis, glucose metabolism, and IGF-1 axis dysregulation in cancer biology (typically as a target for inhibition rather than activation in oncology contexts).

Does Elara test every batch?
Yes. Every production batch of IGF-1 LR3 receives independent third-party HPLC and mass spectrometry analysis before release. Batches that do not meet our 99% purity specification — including verification of correct molecular weight indicating proper disulfide formation — are rejected. The COA documenting analytical results for the specific batch you receive is included with every shipment and available for download above.