What Defines an IGF-1 Protein?
IGF-1 is a small protein hormone. The human gene makes a 195-residue precursor. After the signal peptide and two propeptides are removed, the mature chain is 70 residues long. Three disulfide bonds hold it together [R1]. IGF-1 binds the alpha subunit of the IGF-1 receptor (IGF1R). This switches on the receptor's tyrosine kinase and the PI3K-AKT and Ras-MAPK pathways [R1].
Most IGF-1 in fluids is not free. Six IGF-binding proteins (IGFBP-1 to IGFBP-6) hold it. They can keep IGF-1 away from its receptor. Proteolysis of the IGFBPs can release it again [R4]. So an IGF-1 protein is defined by two things: the IGF-1 core fold and how it partners with IGF1R and the IGFBPs.
Long R3 IGF-1 came out of work by Francis, Ballard and colleagues in Adelaide. They built fusion analogues in E. coli. Each one carried methionine plus the first residues of porcine growth hormone, then Val-Asn, then IGF-1 [R2][R6]. The R3 form also swaps Glu3 for Arg. In rat L6 myoblasts and other cell lines that secrete IGFBPs, the Arg3 analogue was the most potent. In chicken embryo fibroblasts, which secrete no detectable IGFBPs, it was less potent than Long IGF-1. The authors linked the gain to weaker IGFBP binding, not to stronger receptor binding [R2]. Later work by Tomas, Ballard and co-workers in pigs and marmoset monkeys found that IGF-1 variants that bind IGFBPs poorly, including LR3IGF-I, had stronger and longer glucose-lowering effects than native IGF-1 [R5].
IGF-1 Proteins Compared
| Native human IGF-1 | Mecasermin (reference) | Long R3 IGF-1 |
|---|
| Length | 70 amino acids, single chain | 70 amino acids, single chain | 83 amino acids |
|---|
| Modification | None (natural sequence) | None. Recombinant, made in E. coli; sequence identical to human IGF-1 | 13-residue N-terminal extension plus Glu3→Arg |
|---|
| Disulfide bonds | 3 | 3 | 3 (IGF-1 core) |
|---|
| IGFBP binding | Binds the six IGFBPs | Same as native IGF-1 | Reduced |
|---|
| Identifiers (FDA GSRS) | Not listed here | UNII 7GR9I2683O; CAS 68562-41-4 | UNII M9L22Y19H9; CAS 143045-27-6 |
|---|
| Molecular weight | 7649 Da | 7649 Da | About 9111 Da (calculated from sequence) |
|---|
| Status | Endogenous protein | FDA-approved drug substance | Not an approved drug; research reagent |
|---|
Sources: sequence and structure [R1][R2][R6]; mecasermin length, bonds and weight from the FDA label [R9]; identifiers from FDA GSRS [R7][R8]. The Long R3 IGF-1 weight is an average mass we calculated from the verified 83-residue sequence with three disulfide bonds. Lot data can differ, so check the batch report. Our guide on how to read a peptide COA explains each field.
Main Research Use: Cell Culture and Bioprocessing
The largest use of Long R3 IGF-1 is as a media supplement. Many cell lines secrete IGFBPs into the medium. Native IGF-1 can get trapped by them. An analogue with weak IGFBP binding stays more available to the cells [R2]. In serum-free culture of HEK293 cells, Long R3 IGF-1 was reported as a more potent alternative to insulin [R3]. Researchers use it in work on cell growth, survival signalling and recombinant protein production. In most of these studies the model is a cultured cell line, not an animal.
IGF-1 analogues are also tools for receptor biology. Comparing native IGF-1, des(1-3)IGF-1 and the Long analogues helps separate receptor effects from IGFBP effects [R2].
Regulatory Status
Mecasermin is recombinant human IGF-1. Its sequence is identical to the body's own IGF-1. It is the active ingredient of Increlex, first approved by the FDA in 2005. The label covers growth failure in children aged 2 and older with severe primary IGF-1 deficiency, or with GH gene deletion and neutralizing antibodies to GH [R9]. Long R3 IGF-1 is not an approved drug. It has a GSRS substance record, but that is a registry entry, not an approval [R8].
In sport, the 2026 WADA Prohibited List names "Insulin-like growth factor 1 (IGF-1, mecasermin) and its analogues" under S2.3, growth factors and growth factor modulators. Substances in class S2 are banned at all times [R10]. Products here are sold for laboratory research only. Read more in RUO peptides explained.
Frequently Asked Questions
What is the difference between IGF-1 and IGF-1 LR3?
IGF-1 has 70 residues. IGF-1 LR3 has 83. It carries a 13-residue N-terminal extension and Arg in place of Glu at position 3 of the IGF-1 sequence [R2].
Why does Long R3 IGF-1 bind IGFBPs weakly?
Changes at the N-terminus of IGF-1 alter its fit with IGFBPs. Francis and colleagues tied the higher potency of these analogues in cell culture to reduced IGFBP interactions [R2].
Is IGF-1 LR3 the same as mecasermin?
No. Mecasermin has the native 70-residue IGF-1 sequence [R9]. Long R3 IGF-1 is a modified analogue with its own GSRS record [R8].
Is IGF-1 LR3 approved by the FDA?
No. Only mecasermin is FDA-approved, for severe primary IGF-1 deficiency in children [R9].
Is IGF-1 LR3 banned in sport?
Yes. WADA lists IGF-1 and its analogues under S2.3 of the 2026 Prohibited List [R10].
References
- UniProt Consortium. UniProtKB P05019, Insulin-like growth factor 1 (IGF1), Homo sapiens. rest.uniprot.org/uniprotkb/P05019
- Francis GL, Ross M, Ballard FJ, et al. Novel recombinant fusion protein analogues of insulin-like growth factor (IGF)-I indicate the relative importance of IGF-binding protein and receptor binding for enhanced biological potency. J Mol Endocrinol. 1992;8(3):213-223. doi:10.1677/jme.0.0080213. PMID 1378742.
- Voorhamme D, Yandell CA. LONG R3IGF-I as a more potent alternative to insulin in serum-free culture of HEK293 cells. Mol Biotechnol. 2006;34(2):201-204. doi:10.1385/MB:34:2:201. PMID 17172665.
- Firth SM, Baxter RC. Cellular actions of the insulin-like growth factor binding proteins. Endocr Rev. 2002;23(6):824-854. doi:10.1210/er.2001-0033. PMID 12466191.
- Tomas FM, Walton PE, Dunshea FR, Ballard FJ. IGF-I variants which bind poorly to IGF-binding proteins show more potent and prolonged hypoglycaemic action than native IGF-I in pigs and marmoset monkeys. J Endocrinol. 1997;155(2):377-386. doi:10.1677/joe.0.1550377. PMID 9415072.
- UniProt Consortium. UniProtKB P01248, Somatotropin (GH1), Sus scrofa. rest.uniprot.org/uniprotkb/P01248
- U.S. Food and Drug Administration, Global Substance Registration System. Mecasermin, UNII 7GR9I2683O. precision.fda.gov
- U.S. Food and Drug Administration, Global Substance Registration System. Long-(Arg3)insulin-like growth factor-I, UNII M9L22Y19H9. precision.fda.gov
- U.S. Food and Drug Administration. INCRELEX (mecasermin) injection, prescribing information, NDA 021839, revised 07/2025. accessdata.fda.gov
- World Anti-Doping Agency. The 2026 Prohibited List, World Anti-Doping Code (official reprint, Tractatenblad 2026, 25, Kingdom of the Netherlands). zoek.officielebekendmakingen.nl
For laboratory research use only. Not for human or veterinary use.
