IGF-1 LR3 (Long R3 IGF-1): Research Overview, Mechanisms, and Current Evidence
IGF-1 LR3 (Long R3 IGF-1) is a synthetic analog of insulin-like growth factor-1. It carries an arginine substitution at position 3 and a 13-amino-acid N-terminal extension, changes that lower its binding to IGF binding proteins and extend its activity compared with native IGF-1. It is used mainly as a research reagent in cell and animal studies of growth and metabolism. The information below summarizes published research for educational and research purposes only. It is not medical advice and is not guidance for use in humans.
Available for research use from our preferred vendor, Project Zero. For laboratory research use only.
How It Works (Preclinical Mechanisms)
In preclinical models, IGF-1 LR3 has been reported to activate IGF-1 receptor signaling more persistently than native IGF-1 because it largely evades IGF binding proteins.
- Activates the IGF-1 receptor and downstream pathways such as PI3K to AKT, linked to cell growth and survival.
- Binds IGF binding proteins weakly, which is reported to prolong its activity relative to native IGF-1.
- Studied for promoting proliferation and differentiation of muscle cells in culture.
- Investigated for effects on body composition and tissue growth in animal models.
Areas of Research Interest
Published studies have examined IGF-1 LR3 in the following research contexts. The evidence is preclinical, drawn from cell-culture and animal models.
Skeletal muscle research
Studied in muscle-cell cultures and cachexia models for effects on differentiation and muscle mass.
Neuroscience models
Investigated in Alzheimer's disease mouse models for effects on amyloid pathology and body composition.
Cell proliferation
Used as a potent IGF-1 analog to study proliferation signaling in various cell types.
Growth and metabolism
Examined in animal models for effects on lactation, tissue growth, and metabolic signaling.
Reported Study Parameters
For laboratory research use only. The table below reports the doses and routes used in specific published studies, with sources. It describes what researchers administered in these models and is not a protocol, recommendation, or guidance for use in humans or animals. Animal-study doses are expressed per animal or per kilogram of body weight as reported.
| Research Model | Dose and Route Reported | Source |
|---|---|---|
| Skeletal muscle cells (C2C12, in vitro) | 5, 10, 20, or 30 ng/mL in culture medium | Levolger 2019·DOI |
| Cancer cachexia (mouse) | 200 ug per mouse by injection, every other day; limited muscle loss but accelerated tumor growth | Levolger 2019·DOI |
| Human research | No validated clinical regimen established; IGF-1 LR3 is used as a research analog and is not an approved drug | Lu 2023·DOI |
Products are supplied as lyophilized powder requiring reconstitution. For reconstitution concentration math, use the Peptide Calculator.
Latest Research (2019 to 2024)
Recent peer-reviewed literature indexed on PubMed continues to characterize IGF-1 LR3 in preclinical settings, including findings that highlight potential risks alongside benefits.
Alzheimer's disease model (mouse)
A 2024 study reported that 7 months of intranasal LR3-IGF-1 in 5XFAD mice improved body composition and remodeled amyloid plaques in the cortex but did not preserve cognition, leading the authors to caution against its use as a single therapy. PubMed·DOI
Cancer cachexia and muscle wasting (mouse)
A 2019 study reported that LR3 IGF-1 limited loss of muscle mass in a mouse cancer cachexia model but did so at the expense of accelerated tumour growth, an important safety signal for IGF-1 pathway activation. PubMed·DOI
Recombinant production and bioactivity
A 2023 study produced recombinant IGF-1 and LR3 IGF-1 in a yeast expression system and reported that the purified analog showed cell-proliferation bioactivity comparable to standard IGF-1. PubMed·DOI
Lactation and growth signaling (mouse)
A 2008 study reported that subcutaneous Long R3 IGF-1 modestly increased lactation capacity in mice and raised mammary phospho-AKT signaling, illustrating the analog's growth-related effects in vivo. PubMed·DOI
Research Questions
How does IGF-1 LR3 differ from native IGF-1?
IGF-1 LR3 has an arginine substitution and an N-terminal extension that reduce its binding to IGF binding proteins, which is reported to give it more persistent activity than native IGF-1 in preclinical models.
What is the current state of human evidence?
There is no validated human regimen. The published evidence is preclinical, from cell-culture and animal studies, and IGF-1 LR3 is treated as a research analog rather than an approved therapy.
What does the available safety literature suggest?
Activation of the IGF-1 pathway has been associated with accelerated tumour growth in at least one mouse model, which is a notable safety consideration. Human safety has not been established.
Referenced Citations
Literature indexed on PubMed.
- Engel, M.G., et al. (2024). Intranasal long R3 insulin-like growth factor-1 treatment promotes amyloid plaque remodeling in cerebral cortex but fails to preserve cognitive function in male 5XFAD mice. J. Alzheimers Dis., 103(1), 113-126. PubMed·DOI
- Lu, Z., et al. (2023). Recombinant expression of IGF-1 and LR3 IGF-1 fused with xylanase in Pichia pastoris. Appl. Microbiol. Biotechnol., 107(14), 4543-4551. PubMed·DOI
- Levolger, S., et al. (2019). Inhibition of activin-like kinase 4/5 attenuates cancer cachexia associated muscle wasting. Sci. Rep., 9(1), 9826. PubMed·DOI
- Hadsell, D.L., et al. (2008). Enhancement of maternal lactation performance during prolonged lactation in the mouse by mouse GH and long-R3-IGF-I is linked to changes in mammary signaling and gene expression. J. Endocrinol., 198(1), 61-70. PubMed·DOI
PeptideInfo.org provides information strictly for educational and research purposes. All referenced products are intended for laboratory and research use only and are not approved for human consumption, medical use, or self-administration. Nothing on this page constitutes medical advice. Research summaries reference literature indexed on PubMed.