IGF1-LR3

Overview

IGF1-LR3 (Long-Arg³ Insulin-like Growth Factor-1) is an 83-amino-acid synthetic analog of human IGF-1 modified by the addition of a 13-amino-acid N-terminal extension and substitution of arginine for glutamic acid at position 3 of the native IGF-1 sequence. These structural modifications dramatically reduce binding affinity for IGF-binding proteins (IGFBPs), extending the molecule’s circulating half-life and biological activity in preclinical research models (Tomas et al., 1993 — PMID: 8425977).

History

IGF1-LR3 was developed in the early 1990s as part of research efforts to design IGF-1 analogs with prolonged biological activity. The native IGF-1 protein has a short circulating half-life because over 99% of plasma IGF-1 binds to one of six IGF-binding proteins, particularly IGFBP-3, which sequesters the molecule. The Long-Arg³ modifications dramatically reduce IGFBP binding while preserving IGF-1 receptor (IGF-1R) affinity, resulting in a more bioavailable research tool for investigating IGF-1 axis biology (Francis et al., 1992).

Structure & Molecular Data

CAS Number	946870-92-4
Molecular Formula	C₄₀₀H₆₂₅N₁₁₁O₁₁₅S₉
Molecular Weight	9,117.4 g/mol
Amino Acid Count / Structure	83-amino-acid modified IGF-1 analog
PubChem CID	16132340
Sequence	Modified human IGF-1 with N-terminal 13-amino-acid extension and Arg³ substitution (Long-Arg³-IGF-1)
Appearance	Lyophilized white powder
Storage	Store at -20°C. Protect from light.
Solubility	Soluble in dilute acetic acid; reconstitution requires acidified buffer for research preparation

 

Compound Class & Mechanism

IGF1-LR3 binds to the type 1 insulin-like growth factor receptor (IGF-1R), a receptor tyrosine kinase widely expressed across tissue types. Receptor activation in preclinical models has been associated with autophosphorylation of the receptor’s intracellular tyrosine kinase domain and downstream signaling through the PI3K-Akt and MAPK pathways. These pathways have been characterized in research models for their roles in cellular proliferation, survival signaling, and metabolic regulation.

The structural modifications in IGF1-LR3 (Arg³ substitution and N-terminal extension) reduce binding affinity for IGFBP-3 by approximately three orders of magnitude compared to native IGF-1. This results in a substantially larger fraction of free, bioavailable peptide in research preparations, with reported activity potency 2-3× higher than native IGF-1 in certain in vitro models. The modifications also confer extended stability against proteolytic degradation in research conditions (Francis et al., 1992 — PMID: 1639837).

Research Findings

IGF1-LR3 has been investigated in preclinical models spanning growth factor signaling, cellular proliferation research, and metabolic pathway studies. Published research has documented findings in the following domains:

Key Research Areas

• IGF-1R Pathway Research: receptor binding kinetics, downstream PI3K-Akt and MAPK signaling in preclinical models
• Cellular Proliferation: in vitro proliferation studies across multiple cell lines
• Musculoskeletal Models: myocyte differentiation and protein synthesis pathway research
• Comparative IGF-1 Research: stability and bioavailability profile comparisons against native IGF-1

Collectively, the IGF1-LR3 research literature has established the compound as a widely referenced research tool for investigating IGF-1 receptor pharmacology with extended bioavailability characteristics in preclinical environments (Tomas et al., 1993).

Research Context

Researchers study IGF1-LR3 to investigate IGF-1 axis biology in research designs requiring extended peptide bioavailability and reduced IGFBP-mediated sequestration. The compound’s modifications make it a distinct research tool compared to native IGF-1, particularly for in vitro studies where IGFBP confounding effects are undesirable.

References

Francis GL. et al. (1992). Insulin-like growth factor (IGF)-I and IGF-II in human breast carcinoma cells: structural variants. Journal of Molecular Endocrinology. PMID: 1639837

Tomas FM. et al. (1993). The insulin-like growth factor (IGF) analogues IGF-I, des(1-3)IGF-I, and Long-R3-IGF-I, but not bovine IGF-II, increase nitrogen retention in protein-deficient rats. The Journal of Endocrinology. PMID: 8425977

King R. et al. (1992). Insulin-like growth factor: current concepts and new developments in research. Hormone Research.

Ballard FJ. et al. (1991). Estimation of the level of IGF-binding proteins in serum and other biological fluids. Journal of Endocrinology.

Tomas FM. et al. (1993). Anabolic effects of insulin-like growth factor-I (IGF-I) and an IGF-I variant in normal female rats. Journal of Endocrinology.

Walton PE. et al. (1995). The IGFs and IGF-binding proteins in growth and metabolism. Domestic Animal Endocrinology.

 

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