IGF-1 LR3
IGF-1 LR3 is a recombinant analogue of insulin-like growth factor 1 with an arginine substitution at position 3 and a 13-residue N-terminal extension. It binds IGF-binding proteins weakly and is widely used in cell culture.
Most published evidence on IGF-1 LR3 comes from animal and cell studies. Findings in those models have not been established in people.
Overview
IGF-1 LR3 (Long R3 IGF-I) is an engineered form of human insulin-like growth factor 1, the hormone that mediates many of the growth-promoting effects of growth hormone. It was developed in Australia in the late 1980s and early 1990s during research into why some IGF-1 variants were more potent in cell culture than native IGF-1. The answer lay in reduced binding to IGF-binding proteins, which normally sequester IGF-1.
IGF-1 LR3 is best known as a cell culture supplement in research and biomanufacturing, where it supports growth of mammalian cells in serum-free media. It has been studied in animal models of growth and gut adaptation, but there is no meaningful clinical evidence in humans, and it is not an approved drug. The approved IGF-1 medicine, mecasermin (Increlex), is native-sequence recombinant IGF-1, not LR3.
Structure
IGF-1 LR3 is an 83-residue protein comprising the 70-residue human IGF-1 sequence with glutamate at position 3 replaced by arginine, plus a 13-amino-acid N-terminal extension peptide. Like native IGF-1, it contains three intramolecular disulfide bonds that must be correctly paired for activity. It is produced by recombinant expression, typically in E. coli, followed by refolding and purification, rather than by solid-phase synthesis.
Mechanism
IGF-1 LR3 activates the type 1 IGF receptor (IGF-1R), a receptor tyrosine kinase that signals through the PI3K–Akt and MAPK pathways to promote cell growth, proliferation and survival. It also has weaker activity at the insulin receptor. Its intrinsic receptor affinity is broadly similar to or somewhat lower than that of native IGF-1.
The key difference is its markedly reduced affinity for IGF-binding proteins (IGFBPs). In serum and culture media, IGFBPs bind native IGF-1 and limit its availability. Because IGF-1 LR3 escapes much of this binding, more of it remains free to act on receptors, which explains its higher apparent potency in cell culture and its longer activity in animal studies.
Research
Cell culture and biomanufacturing
The most established use of IGF-1 LR3 is as a defined, animal-component-free growth factor in serum-free media for mammalian cell lines, including those used to produce therapeutic proteins. In this setting it can replace insulin or serum to support cell growth and productivity. This is an in-vitro application with extensive industrial use, distinct from any biological use in animals or people.
Growth and metabolism in animal models
Studies in rats, pigs and other animals examined the effects of IGF-1 LR3 on body growth, organ weight and protein metabolism, generally finding more potent effects than native IGF-1, consistent with reduced IGFBP binding. These studies also highlighted hypoglycemia as an expected effect of IGF-1 receptor and insulin receptor activation. Findings are from animal models only. Effects on blood glucose were also monitored in these animal studies.
Gut adaptation research
Animal studies, particularly in rodent and piglet models of intestinal injury and short bowel, investigated whether IGF-1 analogues including LR3 promote intestinal growth and repair. Some studies reported increased gut mass and mucosal growth. This work remains preclinical, and no human trials of IGF-1 LR3 for gastrointestinal conditions have established efficacy or safety. Translational interpretation is further limited by differences in gut physiology between species.
Regulatory status
IGF-1 LR3 is not approved by the FDA or other major regulators for any human or veterinary therapeutic use. It is supplied as a research and cell culture reagent. The only FDA-approved IGF-1 product is mecasermin (Increlex), which has the native IGF-1 sequence. IGF-1 and its analogues are prohibited at all times under section S2 of the WADA Prohibited List.
Status changes often. See the regulatory tracker for dated updates.
Quality and identity testing
Because IGF-1 LR3 is a recombinant protein, a COA should report identity by intact mass spectrometry, with the observed mass matching the expected mass shown on this page, and purity by reverse-phase HPLC and SDS-PAGE. Correct disulfide pairing is critical; misfolded isomers can share the same mass, so peptide mapping or a functional cell proliferation assay adds confidence. Truncated forms lacking the N-terminal extension, oxidized methionine, aggregates and host cell protein or endotoxin contamination from E. coli expression are the main pitfalls. The COA should also state whether the material is the LR3 variant rather than native IGF-1 or des(1-3) IGF-1.
Open IGF-1 LR3 in the sequence analyzer to see the expected [M+H]+ and multiply charged ions for an MS identity check (set the N-acetyl, amide and disulfide options to match).
For a walkthrough of each section of a certificate, see how to read a COA.
Storage and stability
Store lyophilized IGF-1 LR3 at -20 °C or below, sealed and protected from moisture. As a folded protein, it is more sensitive to aggregation and surface adsorption than small peptides. Cell culture suppliers commonly reconstitute it in dilute acid (for example, 10 mM HCl) and may add a carrier protein for dilute stocks; follow the reconstitution recommendations for the specific material. Aliquot and store solutions frozen, avoid repeated freeze-thaw cycles, and use low-binding tubes.
Download the IGF-1 LR3 data sheet (PDF): sequence, masses, expected MS ions and handling on one printable page.
Latest research
The newest PubMed-indexed papers that mention IGF-1 LR3 in their title or abstract, retrieved through Europe PMC and refreshed automatically. Inclusion is not an endorsement of a paper's findings.
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Frequently asked questions
What is the difference between IGF-1 LR3 and IGF-1?
Native IGF-1 has 70 amino acids. IGF-1 LR3 has an arginine in place of glutamate at position 3 and a 13-residue N-terminal extension, giving 83 residues. These changes greatly reduce binding to IGF-binding proteins, so more remains free to act on receptors, giving higher apparent potency in cell culture and animal studies.
Is IGF-1 LR3 FDA approved?
No. IGF-1 LR3 is not approved for any therapeutic use. It is a research and cell culture reagent. The FDA-approved IGF-1 medicine is mecasermin (Increlex), a recombinant form of native human IGF-1 with a specific pediatric indication. Mecasermin and IGF-1 LR3 should not be treated as interchangeable.
Is IGF-1 LR3 a peptide or a protein?
At 83 amino acids with three disulfide bonds and a defined folded structure, IGF-1 LR3 is usually classed as a small protein. It is produced by recombinant expression rather than chemical peptide synthesis, which affects how its quality should be assessed, including folding, host cell impurities and endotoxin. It should be handled as a protein reagent.
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References
- PubMed: all indexed literature on IGF-1 LR3
- ClinicalTrials.gov: registered studies mentioning IGF-1 LR3
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