Description
Summary Abstract
IGF-1 LR3 (Long Arg3 insulin-like growth factor-1; CAS 946870-92-4) is a recombinant synthetic analog of human insulin-like growth factor 1 (IGF-1) engineered with two structural modifications: (1) a 13-amino-acid N-terminal extension and (2) a glutamic acid to arginine substitution at position 3 (Glu³→Arg). These modifications substantially reduce affinity for insulin-like growth factor-binding proteins (IGFBPs) — which sequester native IGF-1 in circulation and limit its bioavailability — while maintaining full agonist activity at the type 1 IGF receptor (IGF-1R). The result is an extended plasma half-life of approximately 20–30 hours (versus ~12 minutes for native IGF-1) and enhanced bioavailability in cell and tissue research systems. IGF-1 LR3 activates downstream PI3K/Akt and MAPK/ERK signaling cascades, driving cellular proliferation, differentiation, protein synthesis, glucose uptake, and survival across multiple tissue types relevant to muscle biology, oncology, diabetes, and growth research.
Clinical Indications
IGF-1 LR3 is a principal tool compound across cell biology, metabolism, and somatotropic axis research:
- Skeletal Muscle Biology: Activates PI3K/Akt/mTOR-dependent protein synthesis and satellite cell proliferation in myotube and primary muscle cell models; widely used to study muscle hypertrophy, atrophy prevention, and anabolic signaling pathways.
- Metabolic Research: Drives GLUT4 translocation and glucose uptake in adipocytes and myotubes via PI3K/Akt; used in insulin resistance and metabolic syndrome models; at concentrations exceeding IGF-1R capacity, can engage the insulin receptor (IR) directly.
- Oncology / Cell Proliferation: IGF-1R is overexpressed in multiple cancer types; IGF-1 LR3 is used as a positive control and pathway activator in receptor-targeted oncology research, enabling dissection of IGF-1R vs. IR signaling in tumor cell biology.
Contraindications
- IGFBP-Dependent Assay Systems: The defining feature of IGF-1 LR3 is its reduced IGFBP affinity; experimental designs that rely on IGFBP-regulated IGF-1 bioavailability (e.g., serum-containing systems studying IGFBP biology) will yield results non-comparable to native IGF-1 controls.
- Insulin Receptor Cross-Activation: At suprapharmacological concentrations, IGF-1 LR3 engages the insulin receptor; glucose homeostasis experiments should include receptor-specific controls and appropriate concentration range validation to distinguish IGF-1R from IR-mediated effects.
- Hypoglycemia Risk in In Vivo Models: The extended half-life and insulin-like signaling of IGF-1 LR3 can produce hypoglycemia in rodent in vivo models at doses above 1 mg/kg; blood glucose monitoring should be built into all acute and chronic in vivo dosing protocols.
Mechanism of Action (MOA)
IGF-1 LR3 acts as a full IGF-1R agonist with the pharmacokinetic advantages of IGFBP resistance:
IGF-1R Activation
IGF-1 LR3 binds the type 1 IGF receptor (IGF-1R) with affinity comparable to native IGF-1, inducing receptor autophosphorylation and recruitment of IRS-1/IRS-2 adaptor proteins. The N-terminal extension does not contact the receptor binding interface and thus does not impair agonist activity; the Arg³ substitution is the primary determinant of reduced IGFBP binding.
PI3K/Akt/mTOR Anabolic Signaling
IGF-1R activation drives PI3K-dependent phosphorylation of Akt, which activates mTORC1 through TSC1/2 inhibition and direct RAPTOR phosphorylation. mTORC1 activation increases ribosomal S6 kinase (S6K1) and 4E-BP1 phosphorylation, accelerating translational capacity. This pathway is the primary mediator of IGF-1-driven protein synthesis and anabolic hypertrophy in skeletal muscle.
MAPK/ERK Proliferative Signaling
Parallel to Akt, IGF-1R activates the Ras-Raf-MEK-ERK cascade through Shc/Grb2/SOS. ERK1/2-driven transcriptional regulation promotes cellular proliferation, differentiation, and survival, contributing to IGF-1’s mitogenic and anti-apoptotic activities in cell culture models across epithelial, neuronal, and musculoskeletal cell types.
IGFBP Resistance and Extended Bioavailability
Native IGF-1 circulates predominantly in ternary complexes with IGFBP-3/ALS, which limit its tissue access; the Glu³→Arg substitution in LR3 sharply reduces affinity for IGFBPs 1–6. This IGFBP resistance extends the effective plasma half-life to approximately 20–30 hours and eliminates the competitive binding interference that complicates quantitative cell culture experiments using native IGF-1 in serum-containing media.
Key Features & Specifications
IGF-1 LR3 is supplied as a 1 mg lyophilized 83-amino-acid recombinant peptide for cell biology, metabolic, and somatotropic research:
Chemical Analysis
| Property | Specification Reference Data |
|---|---|
| Sequence | MFPAMPLSSLFVNGPRTLCGAELVDALQFVCGDRGFYFNKPTGYGSSSRRAPQTGIVDECCFRSCDLRRLEMYCAPLKPAKSA (83 aa; N-terminal 13-aa extension + full IGF-1 sequence with Glu³→Arg substitution) |
| CAS Number | 946870-92-4 |
| Molecular Formula | C400H625N111O115S9 |
| Molecular Weight | 9,117.6 g/mol (9.1 kDa) |
| Synonyms | Long Arg3-IGF-1; LR3-IGF-1; [Arg3]-IGF-1; recombinant IGF-1 LR3 |
| PubChem CID | — |
| Form / Variation | 1 MG Lyophilized (SKU P-020) |
Storage, Safety, and Handling
Storage Protocol
Store lyophilized IGF-1 LR3 at −20 °C in a desiccated environment; protect from repeated freeze–thaw cycles. Following reconstitution in sterile 0.1% acetic acid or phosphate-buffered saline with 0.1% bovine serum albumin (BSA) as a carrier, working aliquots are stable at 4 °C for up to 14 days. Single-use aliquots at −80 °C minimize degradation from repeated handling.
Handling & Compliance
Reconstitute using standard aseptic technique; avoid vortexing — gently invert or roll the vial to dissolve. Adsorption to uncoated plasticware is significant at low concentrations; use low-binding tubes and add a BSA carrier when working below 10 ng/mL. IGF-1 LR3 is listed on the World Anti-Doping Agency (WADA) Prohibited List under the category of Peptide Hormones and Growth Factors. Comply with applicable institutional and national regulations governing its acquisition and use.