IGF-1 LR3: 83 residues, and how it differs from IGF-1

IGF-1 LR3, also written Long R3 IGF-1, is an 83-residue analogue of human insulin-like growth factor 1. It is the 70 residues of IGF-1 with arginine in place of glutamic acid at position 3, behind a 13-residue N-terminal extension, MFPAMPLSSLFVN. It was described in 1992 by an Adelaide group as a laboratory reagent for studying IGF-1, and its two changes make it bind the IGF-binding proteins far less than IGF-1 does. No drug containing it is approved in the United States; the IGF-1 drug FDA has approved, mecasermin, is unmodified recombinant human IGF-1. Ours is sold for laboratory research use only.

Where it came from

Two papers in the Journal of Molecular Endocrinology in 1992 set it out. King and colleagues at the University of Adelaide made recombinant IGF-1 and two variants in which glutamic acid 3 was replaced by glycine or arginine, and found that both variants "bound very poorly" to an IGF-binding protein while binding the type 1 IGF receptor "slightly less well than IGF-I". Francis and colleagues, at the CSIRO Division of Human Nutrition in Adelaide, then put an N-terminal extension in front: "the first 11 amino acids of methionyl porcine growth hormone" followed by Val-Asn. With arginine at position 3, that molecule was named Long [Arg3]-IGF-I. They described these analogues as "very useful reagents in the investigation of IGF-I action."

The cell-culture work in the Francis paper shows what the change does. In cell lines that secrete IGF-binding proteins into the medium, Long [Arg3]-IGF-I ranked with des(1-3)IGF-I as the most potent of the forms tested; in chicken embryo fibroblasts, which secrete no detectable binding proteins, it was less potent than IGF-I. The authors concluded that the gain came "due to changes in the degree of their IGFBP interactions", not from stronger receptor binding.

The 83 residues

Human IGF-1 is residues 49 to 118 of its precursor in UniProt (P05019): 70 residues beginning Gly-Pro-Glu. IGF-1 LR3 changes the third of those to arginine and adds the extension in front:

MFPAMPLSSLFVN GPR TLCGAELVDALQFVCGDRGFYFNKPTGYGSSSRRAPQTGIVDECCFRSCDLRRLEMYCAPLKPAKSA

The first block is the extension (the first 11 residues of methionyl porcine growth hormone, MFPAMPLSSLF, then Val-Asn), the second is IGF-1's first three residues with arginine at position 3, and the rest is unchanged human IGF-1.

IGF-1 is held in shape by three disulfide bonds, which UniProt places between cysteines 6 and 48, 18 and 61, and 47 and 52 of the mature chain. In IGF-1 LR3 numbering, 13 places later, those are cysteines 19 and 61, 31 and 74, and 60 and 65. The solution structure published in 2000 (Laajoki and colleagues, PDB 3LRI) found the IGF-1 part folded much as IGF-1 is. The largest difference was a substantial reorientation of the first three IGF-1 residues, which the authors linked to its lower affinity for the binding proteins; the extension itself was flexible.

Formula and mass

With its three disulfide bonds formed, as in the folded protein, IGF-1 LR3 is C400H619N111O115S9: an average molecular weight of 9111.5 and a monoisotopic mass of 9105.35. If the six cysteines are counted as free thiols instead, the formula gains six hydrogens, C400H625N111O115S9, and the average mass becomes 9117.5. A listing that gives 9117 is counting the cysteines as free thiols.

That 6 Da gap is something a mass spectrum can see. By electrospray the protein appears as a series of multiply charged ions; the folded form gives, for example, m/z 4553.68 with two protons and 3036.12 with three, where the reduced form would sit at 4556.71 and 3038.14. Deconvolved, a correctly folded lot should land near 9111, not 9117. Our guide to mass spectrometry and peptide identity covers deconvolution.

Its size is also why it is sold by the milligram rather than in tens of milligrams: at 83 residues it is the longest chain in our catalogue. Milligrams, micrograms and units explains the arithmetic.

IGF-1 LR3, IGF-1 and mecasermin

Mecasermin is the name for recombinant human IGF-1 as a drug, the same sequence as natural IGF-1. IGF-1 LR3 is a different molecule.

US status as of November 7, 2026

No approved product. A search of Drugs@FDA, FDA's database of approved drugs, by active ingredient returns no product containing IGF-1 LR3. The IGF-1 products it does list contain mecasermin: Increlex (BLA 021839, Ipsen, approved August 30, 2005, marketed by prescription) and the discontinued Iplex (mecasermin rinfabate, BLA 021884).

A protein, by FDA's definition. Federal regulations define a protein as "any alpha amino acid polymer with a specific, defined sequence that is greater than 40 amino acids in size" (21 CFR 600.3(h)(6)), and proteins are regulated as biological products. At 83 residues IGF-1 LR3 is well past that line, as IGF-1 itself is: Drugs@FDA records that Increlex, a former new drug application, was deemed to be a BLA on March 23, 2020.

Sport. The World Anti-Doping Agency's 2026 Prohibited List names "Insulin-like growth factor 1 (IGF-1, mecasermin) and its analogues" in section S2.3, prohibited at all times. IGF-1 LR3 is an analogue of IGF-1. See our summary of the Prohibited List and research peptides.

Research material is sold for laboratory research use only and is not for human or veterinary use.

What our certificate shows

Our 1 mg size has a current certificate of analysis from Bioviridian Inc., the testing laboratory: lot IGF1LR3-1-0803, 99.55% purity by reversed-phase HPLC at 214 nm, identity by LC-MS/MS reported as conforming, and a measured content of 1.12 mg. It is certificate COA7588, issued August 28, 2026. An earlier lot, IGF1LR3-1-0528, is kept as an archived certificate: 99.9% purity, identity by MALDI-MS, issued June 17, 2026.

Common questions

What is IGF-1 LR3?

An 83-residue analogue of human IGF-1, made with arginine at position 3 and a 13-residue N-terminal extension so that it binds IGF-binding proteins far less than IGF-1. It was described in 1992 as a laboratory reagent.

Is IGF-1 LR3 FDA approved?

No. Drugs@FDA lists no product containing it (checked November 7, 2026). The approved IGF-1 drug, mecasermin (Increlex), is unmodified recombinant human IGF-1, a different molecule.

What is the difference between IGF-1 LR3 and IGF-1?

Two changes: glutamic acid 3 is replaced by arginine, and 13 residues (MFPAMPLSSLFVN) are added in front. IGF-1 has 70 residues and IGF-1 LR3 has 83; their average masses are about 7649 and 9111.

What is the molecular weight of IGF-1 LR3?

About 9111.5 (C400H619N111O115S9) with its three disulfide bonds formed. The figure 9117.5 (C400H625N111O115S9) counts the cysteines as free thiols.

Does IGF-1 LR3 need to be refrigerated?

Our IGF-1 LR3 is supplied as a lyophilized powder and listed for storage at -20 °C, desiccated. General handling is covered in storage and stability.

Sources

• UniProt P05019, Insulin-like growth factor 1 (human), UniProt Consortium
• King R, Wells JR, Krieg P, et al. Production and characterization of recombinant insulin-like growth factor-I (IGF-I) and potent analogues of IGF-I, with Gly or Arg substituted for Glu3. J Mol Endocrinol, 1992
• 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
• [Laajoki LG, Francis GL, Wallace JC, et al. Solution structure and backbone dynamics of long-[Arg(3)]insulin-like growth factor-I. J Biol Chem, 2000](https://pubmed.ncbi.nlm.nih.gov/10744677/)
• [PDB 3LRI, Long-[Arg3]-IGF-I solution structure, RCSB Protein Data Bank](https://www.rcsb.org/structure/3LRI)
• 21 CFR 600.3, Definitions, eCFR
• Drugs@FDA: BLA 021839, Increlex, FDA
• The 2026 Prohibited List (PDF), World Anti-Doping Agency, valid January 1, 2026
• openFDA drugsfda endpoint, searched by active ingredient, FDA, November 7, 2026