Description

IGF-1 LR3 (Insulin-like Growth Factor-1 Long R3)

IGF-1 LR3 (Long R3 Insulin-like Growth Factor-1) is a synthetic 83-amino acid analogue of human insulin-like growth factor-1 (IGF-1) engineered for enhanced potency and prolonged bioactivity relative to the native 70-amino acid IGF-1 peptide. The LR3 variant incorporates two modifications: substitution of arginine (R) for glutamate at position 3 (reducing binding to IGF-binding proteins), and a 13-amino acid N-terminal extension. Molecular formula: C990H1528N262O300S7; CAS No. 946870-92-4. IGF-1 LR3 exhibits approximately 2-3 times greater in vitro potency than native IGF-1 and a markedly extended half-life due to dramatically reduced affinity for IGF-binding proteins (IGFBPs), which in vivo sequester and inactivate native IGF-1. It is provided as a lyophilized powder for reconstitution in acidified aqueous buffers.

Mechanism of Action

IGF-1 LR3 exerts its activity through the type 1 IGF receptor (IGF-1R), a receptor tyrosine kinase with widespread expression across muscle, bone, adipose, liver, brain, and other tissues. IGF-1R activation triggers receptor autophosphorylation and downstream signaling through two primary pathways:

• PI3K/AKT/mTOR pathway: Phosphoinositide 3-kinase (PI3K) activation leads to AKT phosphorylation and downstream mTOR complex 1 (mTORC1) activation, promoting protein synthesis, cell survival (anti-apoptosis), and glucose transporter (GLUT4) translocation to the membrane in muscle and adipose cells.
• RAS/MAPK pathway: Ras GTPase activation downstream of IRS-1 drives ERK1/2 signaling, stimulating cell proliferation, differentiation, and migration in culture and in vivo models.

The key experimental advantage of IGF-1 LR3 over native IGF-1 is its minimal affinity for the six known IGFBPs (IGFBP-1 through IGFBP-6), which in vivo bind more than 99% of circulating native IGF-1, limiting its bioavailability. IGF-1 LR3’s reduced IGFBP binding means it remains in the biologically active, unbound state at higher proportions, producing greater receptor occupancy per unit dose in experimental models. This property also extends its half-life from the approximately 10-minute half-life of free IGF-1 to 20-30 hours for IGF-1 LR3 in animal studies.

Observed Effects in Preclinical Research

In vitro studies demonstrate that IGF-1 LR3 potently stimulates protein synthesis in skeletal muscle myotubes, inhibits protein degradation (anti-catabolic effects), and promotes myoblast differentiation and satellite cell activation. In cell proliferation assays, IGF-1 LR3 produces concentration-dependent increases in DNA synthesis across diverse cell types including myocytes, osteoblasts, chondrocytes, and neural cells. In rodent models, systemic and local administration of IGF-1 LR3 has been associated with increases in lean muscle mass, enhanced bone mineral density in metaphyseal regions, accelerated wound and fracture healing, and neuroprotective effects in traumatic brain injury models. In IGF-1-deficient animal models (Laron dwarf mice), IGF-1 LR3 administration normalized growth parameters and metabolic function.

Research Applications

IGF-1 LR3 is widely used as a research tool in cell culture systems requiring sustained IGF-1R stimulation, serum-free and low-serum cell culture media formulations, preclinical models of muscle wasting and sarcopenia, skeletal muscle hypertrophy and protein synthesis pathway studies, bone formation and osteoblast biology, neuronal survival and neuroprotection studies, IGF-1R signaling characterization and downstream pathway mapping, and metabolic studies involving insulin/IGF-1 axis cross-talk.

Peptide Characteristics

Note: A current Certificate of Analysis for this product was not available from our reference source at time of publication. Contact StandardLabz for current lot COA documentation.

FOR RESEARCH USE ONLY. NOT FOR HUMAN USE. NOT INTENDED FOR DIAGNOSIS, TREATMENT, OR PREVENTION OF ANY CONDITION.