What Is IGF-1 LR3?
IGF-1 LR3 (Insulin-like Growth Factor-1 Long Arg3) is a synthetic 83-amino acid analogue of native IGF-1 engineered for enhanced research utility. Two modifications distinguish it from endogenous IGF-1: an N-terminal 13-amino acid extension and an arginine substitution at position 3. Together, these changes reduce IGF-1 LR3’s affinity for IGF-binding proteins (IGFBPs) by approximately 1,000-fold compared to native IGF-1 — dramatically extending its half-life in research models and increasing the proportion of biologically active compound available at the receptor level.
Molecular Structure and Properties
- Full name: Long Arg3 IGF-1
- Amino acids: 83 (vs 70 in native IGF-1)
- Molecular weight: ~9,117 Da
- Key modifications: 13-aa N-terminal extension; Arg substitution at position 3
- Half-life advantage: Native IGF-1 half-life in serum ~10–20 min (IGFBP-bound); IGF-1 LR3 ~20–30 hours in vitro
- Supplied as: lyophilised powder for in vitro research use
Mechanism of Action: IGF-1R Signalling
IGF-1 LR3 binds the IGF-1 receptor (IGF-1R), a transmembrane tyrosine kinase receptor. Receptor activation initiates two major downstream signalling cascades studied extensively in cell biology:
PI3K/AKT/mTOR pathway:
- IGF-1R activation recruits IRS-1/IRS-2 adaptor proteins
- IRS phosphorylation activates phosphoinositide 3-kinase (PI3K)
- PI3K generates PIP3, recruiting and activating AKT (protein kinase B)
- AKT activates mTORC1, promoting protein synthesis, cellular hypertrophy, and inhibition of protein degradation
- AKT also phosphorylates FOXO transcription factors, reducing atrogene expression
MAPK/ERK pathway:
- IGF-1R activates Ras via Grb2/SOS
- Ras activates the Raf/MEK/ERK cascade
- ERK1/2 nuclear translocation promotes cell cycle progression and proliferation
IGFBP Resistance and Research Utility
Endogenous IGF-1 circulates predominantly bound to IGFBP-3 and the acid-labile subunit (ALS), with only ~1% free at any given time. In cell culture and in vitro models, IGFBPs present in serum can sequester exogenous IGF-1, reducing its effective concentration at the receptor.
IGF-1 LR3’s dramatically reduced IGFBP affinity means that in serum-containing in vitro models, a far higher proportion of added compound reaches the receptor in its active form. This makes IGF-1 LR3 the preferred analogue for cell culture research where consistent, quantifiable receptor activation is required.
Key Research Areas
Skeletal muscle cell biology: IGF-1 LR3 is widely used in myoblast and satellite cell culture models. It promotes myoblast proliferation via MAPK/ERK and differentiation into myotubes via PI3K/AKT/mTOR — making it a standard tool in muscle biology research.
Protein synthesis research: mTORC1 activation downstream of IGF-1R is the central regulator of ribosomal protein synthesis. IGF-1 LR3 is used to study mTOR-dependent translation in cell-free and cell-culture systems.
Insulin-like metabolic signalling: IGF-1R shares ~70% homology with the insulin receptor and can activate overlapping metabolic pathways. IGF-1 LR3 is used in models examining glucose uptake, GLUT4 translocation, and insulin-like anabolic signalling.
Cancer biology: IGF-1R overexpression and hyperactivation of the PI3K/AKT/mTOR axis are implicated in multiple malignancies. IGF-1 LR3 is used as a tool compound in studies examining IGF pathway dependency and resistance to IGF-1R-targeted therapies.
Sourcing IGF-1 LR3 for Research
R&D Peptides supplies IGF-1 LR3 1mg as a lyophilised research compound with a batch-specific Certificate of Analysis. Supplied strictly for in vitro research use only.
For quality and testing standards, see our quality and testing page.
All content on this page is for educational and informational purposes only. IGF-1 LR3 is supplied by R&D Peptides strictly for in vitro research use. It is not intended for human or veterinary administration, and no therapeutic claims are made or implied.
