IGF-1 LR3

Research Overview

IGF-1 LR3 serves as a valuable research tool for investigating insulin-like growth factor-I receptor signaling and direct anabolic effects independent of growth hormone in laboratory settings. This engineered IGF-I analog incorporates structural modifications that dramatically alter its binding protein interactions while preserving high-affinity IGF-I receptor activation. Research applications have expanded to encompass investigations of muscle protein synthesis pathways, cellular proliferation mechanisms, metabolic regulation, neuroprotection, and tissue regeneration processes downstream of IGF-I receptor activation.

The peptide’s development addressed significant limitations of native IGF-I for research applications. Endogenous IGF-I circulates almost entirely bound to IGF binding proteins (IGFBPs), particularly IGFBP-3, which regulates its bioavailability and half-life. Native IGF-I exhibits a plasma half-life of only 10-20 minutes as free peptide. IGF-1 LR3’s modifications dramatically reduce IGFBP binding affinity, allowing the peptide to remain bioavailable for extended periods and reach tissues more effectively. Laboratory studies investigate IGF-1 LR3’s effects on anabolic signaling, cell survival pathways, metabolic regulation, and tissue-specific growth responses.

IGF-1 LR3 research demonstrates the peptide’s exceptional utility for investigating IGF-I receptor biology independent of the complex regulatory mechanisms governing native IGF-I. The extended half-life and reduced IGFBP binding enable cleaner experimental interpretations of IGF-I receptor-mediated effects. Studies examine the peptide’s actions in cell culture systems, tissue explants, and preclinical animal models assessing anabolic, metabolic, and protective outcomes.

Molecular Characteristics

Complete Specifications:

• CAS Registry Number: 946870-92-4
• Molecular Weight: 9,117.5 Da
• Molecular Formula: C₄₀₀H₆₂₅N₁₁₁O₁₁₅S₉
• Sequence Length: 83 amino acids (native IGF-I is 70 amino acids)
• Modifications: 13-amino acid N-terminal extension + Arg3→Glu substitution
• Peptide Classification: Synthetic IGF-I analog, Long R3 variant
• Appearance: White to off-white lyophilized powder
• Solubility: Dilute acid (0.1M acetic acid), reconstituted with appropriate buffer to neutral pH

The peptide’s structure consists of native IGF-I’s 70-amino acid sequence with two critical modifications. The 13-amino acid N-terminal extension (MFPAMPLSSLFV V) increases molecular size and alters conformational properties affecting IGFBP binding. The Arg→Glu substitution at position 3 further reduces IGFBP affinity, particularly for IGFBP-3 and IGFBP-5. These modifications result in ~100-fold reduced binding to IGFBPs compared to native IGF-I while maintaining full IGF-I receptor activation capability. The peptide retains the three disulfide bonds (A6-A11, A18-A61, A47-A52) essential for structural integrity and receptor binding.

Pharmacokinetic Profile in Research Models

IGF-1 LR3 pharmacokinetic characterization in preclinical research reveals important properties for experimental design:

Extended Half-Life:

• Plasma half-life: Approximately 20-30 hours (versus 10-20 minutes for native IGF-I)
• Dramatically extended due to reduced IGFBP binding
• Enables less frequent dosing in research protocols
• Sustained receptor activation over extended periods

Binding Protein Interactions:

• ~100-fold reduced affinity for IGFBP-3 (primary IGF-I carrier protein)
• Minimal binding to IGFBP-1, -2, -4, -5, -6
• Circulates primarily as free (unbound) peptide
• Enhanced tissue penetration due to reduced sequestration by binding proteins

Tissue Distribution and Activity:

• Enhanced distribution to peripheral tissues
• Sustained IGF-I receptor activation
• Increased biological potency (2-3 fold versus native IGF-I)
• Prolonged downstream signaling pathway engagement

These pharmacokinetic characteristics inform research protocol design, enabling investigation of sustained IGF-I receptor activation effects with convenient dosing schedules while minimizing confounding effects of binding protein regulation.

Research Applications

Anabolic Signaling Pathway Investigation

IGF-1 LR3 serves as a research tool for investigating fundamental anabolic mechanisms. Laboratory studies examine the peptide’s effects on:

• Protein Synthesis Pathways: Investigation of mTOR, PI3K/Akt, and MAPK pathway activation downstream of IGF-I receptor
• Muscle Hypertrophy Research: Studies on myofibrillar protein accretion, muscle fiber size, and satellite cell activation
• Anabolic Gene Expression: Research on myogenic regulatory factors, structural protein genes, and growth-related transcription
• Ribosomal Protein Synthesis: Investigation of translation initiation, elongation, and ribosome biogenesis
• Protein Degradation Inhibition: Studies on ubiquitin-proteasome pathway suppression and muscle protein breakdown

Research protocols typically employ muscle cell cultures (C2C12, primary myoblasts), in vitro protein synthesis assays, and in vivo muscle growth models to characterize anabolic signaling.

Metabolic Regulation Research

Substantial research focuses on metabolic pathway investigation:

• Glucose Uptake Studies: Research on insulin-independent glucose transport activation via IGF-I receptor
• Insulin Sensitivity Research: Investigation of PI3K/Akt pathway effects on insulin signaling enhancement
• Lipid Metabolism Studies: Research on lipolysis, lipogenesis, and fatty acid oxidation regulation
• Glycogen Synthesis Investigation: Studies on glycogen synthase activation and glycogen storage
• Nutrient Partitioning Research: Investigation of substrate utilization and metabolic fuel selection

Laboratory protocols investigate metabolic effects using glucose uptake assays, insulin sensitivity tests, and metabolic tracer studies in cell culture and animal models.

Cell Survival and Neuroprotection Studies

Laboratory studies investigate IGF-1 LR3 in protective pathway research:

• Anti-Apoptotic Signaling: Research on Akt-mediated cell survival pathway activation
• Neuroprotection Studies: Investigation of neuronal protection against excitotoxicity, oxidative stress, and injury
• Neurite Outgrowth Research: Studies on axonal growth, dendritic branching, and synaptic plasticity
• Neurogenesis Investigation: Research on neural progenitor proliferation and differentiation
• Neurodegenerative Model Studies: Investigation of protective effects in experimental models of neurological conditions

Experimental models include neuronal cell cultures, organotypic brain slices, and animal models of neuronal injury or degeneration.

Tissue Regeneration Research Applications

Research applications extend to regenerative process investigation:

• Wound Healing Studies: Examination of tissue repair, cellular migration, and extracellular matrix remodeling
• Satellite Cell Activation: Research on muscle stem cell proliferation, differentiation, and fusion
• Bone Formation Studies: Investigation of osteoblast activity, bone mineral deposition, and skeletal growth
• Cartilage Research: Studies on chondrocyte proliferation, matrix synthesis, and cartilage repair
• Tissue Engineering Applications: Investigation of IGF-I effects on engineered tissue growth and maturation

Laboratory protocols investigate regenerative effects using various tissue injury models, stem cell cultures, and tissue engineering systems.

Aging and Sarcopenia Research

Emerging research areas include age-related investigation:

• Age-Related Muscle Loss: Research on reversing sarcopenia through sustained IGF-I receptor activation
• Anabolic Resistance Studies: Investigation of aged muscle responsiveness to anabolic stimuli
• Cellular Senescence Research: Studies examining IGF-I effects on senescent cell characteristics
• Regenerative Capacity Investigation: Research on tissue repair capability in aging contexts
• Healthspan Extension Studies: Investigation of IGF-I pathway role in longevity and age-related decline

Research in this area examines IGF-1 LR3 effects in aged animal models and contexts of age-related anabolic resistance.

Laboratory Handling and Storage Protocols

Lyophilized Powder Storage:

• Store at -20°C to -80°C in original sealed vial
• Protect from light exposure and moisture
• Desiccated storage environment essential
• Stability data available for 12-24 months at -20°C

Reconstitution Guidelines:

• Initial reconstitution: Dilute acid (0.1M acetic acid) recommended for solubilization
• Secondary dilution: Bring to neutral pH with appropriate buffer (PBS, cell culture medium)
• Add solvent slowly down vial side to minimize foaming
• Gentle swirling motion recommended (avoid vigorous shaking)
• Allow complete dissolution before use (typically 5-10 minutes)
• Final pH should be 7.0-7.5 for cell culture applications

Reconstituted Solution Storage:

• Short-term storage: 4°C for up to 3-5 days
• Long-term storage: -20°C in aliquots to avoid freeze-thaw cycles
• Single-use aliquots strongly recommended
• Avoid repeated freeze-thaw cycles (maximum 2 cycles)
• Consider addition of carrier protein (BSA) for enhanced stability in dilute solutions

Stability Considerations:
IGF-1 LR3 demonstrates good stability as a lyophilized powder under proper storage conditions. The modified structure provides enhanced stability compared to native IGF-I. Reconstituted solutions require careful pH control and prompt use or proper storage. The presence of multiple disulfide bonds necessitates protection from reducing conditions.

Quality Assurance and Analytical Testing

Each IGF-1 LR3 batch undergoes comprehensive analytical characterization:

Purity Analysis:

• High-Performance Liquid Chromatography (HPLC): ≥95% purity
• Analytical method: Reversed-phase HPLC with UV detection at 214nm
• Multiple peak integration to ensure accurate purity determination

Structural Verification:

• Electrospray Ionization Mass Spectrometry (ESI-MS): Confirms molecular weight 9,117.5 Da
• Amino acid analysis: Verifies sequence composition including modifications
• Disulfide bond confirmation
• Peptide content determination: Quantifies actual peptide content by weight

Contaminant Testing:

• Bacterial endotoxin: <5 EU/mg (LAL method)
• Heavy metals: Below detection limits per USP standards
• Residual solvents: TFA and acetonitrile within acceptable limits
• Water content: Karl Fischer titration (<8%)

Documentation:

• Certificate of Analysis (COA) provided with each batch
• Third-party analytical verification available upon request
• Stability data documented for recommended storage conditions
• Batch-specific QC results traceable by lot number

Research Considerations

Experimental Design Factors:

Researchers should consider several factors when designing IGF-1 LR3 experiments:

1. Dose Selection: IGF-1 LR3 demonstrates 2-3 fold greater potency than native IGF-I. Adjust doses accordingly when comparing to native IGF-I studies.

2. Extended Half-Life: The ~24-hour half-life enables once-daily dosing but also necessitates longer washout periods between experimental conditions.

3. IGFBP Independence: Unlike native IGF-I, effects are not modulated by IGFBP levels, enabling cleaner interpretation of IGF-I receptor-mediated effects.

4. Insulin Receptor Cross-Reactivity: At high concentrations, IGF-I can activate insulin receptors. Consider this in metabolic studies.

5. GH Independence: IGF-1 LR3 enables investigation of IGF-I effects independent of GH, valuable for isolating downstream pathway effects.

Mechanism Investigation:

IGF-1 LR3’s mechanisms are well-characterized:

• High-affinity IGF-I receptor (IGF-IR) activation
• Receptor tyrosine kinase autophosphorylation
• PI3K/Akt pathway activation (metabolic and survival effects)
• MAPK/ERK pathway activation (proliferation and differentiation)
• mTOR pathway activation (protein synthesis)
• Glycogen synthase activation (glucose storage)
• Anti-apoptotic signaling (Bcl-2 family regulation)

The peptide’s mechanisms parallel native IGF-I but with enhanced potency and duration due to reduced IGFBP binding.

Compliance and Safety Information

Regulatory Status:
IGF-1 LR3 is provided as a research chemical for in-vitro laboratory studies and preclinical research only. This product has not been approved by the FDA for human therapeutic use, dietary supplementation, or medical applications.

Intended Use:

• In-vitro cell culture studies
• In-vivo preclinical research in approved animal models
• Laboratory investigation of biological mechanisms
• Academic and institutional research applications

NOT Intended For:

• Human consumption or administration
• Therapeutic treatment or diagnosis
• Dietary supplementation
• Veterinary therapeutic applications without appropriate oversight

Safety Protocols:
Researchers should follow standard laboratory safety practices when handling IGF-1 LR3:

• Use appropriate personal protective equipment (lab coat, gloves, safety glasses)
• Handle in well-ventilated areas or fume hood
• Follow institutional biosafety guidelines
• Dispose of waste according to local regulations for biological/chemical waste
• Consult material safety data sheet (MSDS) for additional safety information

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