# IGF-1 LR3

> IGF-1 LR3 (Long R3 IGF-1) is a recombinant analog of insulin-like growth factor 1 that carries an N-terminal extension peptide and an arginine at position 3. These changes sharply reduce its affinity for IGF binding proteins, and in rat studies it proved more potent than native IGF-1. Published research on it is mostly in animals and cell culture.

Canonical: https://peptideproperties.com/compounds/igf-1-lr3/

## Identity

- **Class:** Growth Factors, IGF & Myostatin Pathway
- **Also known as:** Long R3 IGF-1, LR3-IGF-1
- **Sequence notes:** IGF-1 sequence with an arginine at position 3 (the 'R3'), preceded by an N-terminal extension peptide (the 'Long')

## Key facts

- Class: recombinant insulin-like growth factor 1 (IGF-1) analog, a protein
- Structure: IGF-1 with an N-terminal extension peptide and arginine at position 3
- Key property: much reduced affinity for IGF binding proteins (IGFBPs)
- No PubChem compound record; identity is confirmed by mass spectrometry and immunoassay
- Evidence base: rat, pig, guinea pig, cattle and cell-culture studies
- Not approved by the FDA for human use; IGF-1 analogs are banned in sport

## What Is IGF-1 LR3?

IGF-1 LR3 is a modified, longer form of insulin-like growth factor 1 (IGF-1) built to escape the binding proteins that normally restrain IGF-1. Researchers also call it Long R3 IGF-1 or long arginine (LR3) IGF-I, and rat studies established it as more potent than native IGF-1.[1]Its defining property is a much reduced affinity for IGF binding proteins (IGFBPs).[2] Because most circulating IGF-1 is held by these proteins, an analog that binds them poorly behaves differently from the native hormone in living animals. Measuring that difference is the aim of most published studies.The literature on IGF-1 LR3 is almost entirely preclinical. It covers growth and organ weight in rats, guinea pigs and pigs, protein metabolism in cattle, intestinal biology and a few cell-culture experiments. No controlled human trials appear among the indexed studies reviewed for this page.

## Chemical Structure and Molecular Identity

IGF-1 LR3 is a recombinant protein: the IGF-1 sequence with an arginine at position 3 (the "R3") and an extension peptide added to the N-terminus (the "Long"). A 1996 protein-engineering study described it as an N-terminal extended IGF-I analogue and mapped where pepsin cuts both the extension peptide and the IGF-1 portion.[3]In that study, pepsin first cleaved the Leu10-Phe11 bond inside the extension peptide, then several bonds within the IGF-1 moiety. Single-point mutants designed to resist these cuts kept growth-promoting activity equal to or above that of IGF-1, and one variant, Phe16Ala (long-R3A16-IGF-I), showed markedly better pepsin stability.[3]
### Identity and analysis
IGF-1 LR3 has no PubChem compound record, so this page does not list a formula or molecular weight. As a protein, it is characterized by mass spectrometry and immunoassay rather than small-molecule identifiers. A 2010 anti-doping case report used nano-UPLC, high-resolution mass spectrometry of the intact and trypsin-digested protein, and ELISA to identify a vial's contents as Long-R3-IGF-I carrying a C-terminal His6 tag attached through a Leu-Glu linker.[4]

## Research History and Development

IGF-1 LR3 emerged as a research tool for IGF biology, and most of its published history comes from animal studies of the 1990s and early 2000s. Investigators used it to test what happens when an IGF-1 signal arrives in a form that binding proteins cannot easily neutralize.[2][5]Rat work showed growth stimulation, but results in other species diverged. A 1997 pig study noted that IGF-1 analogs binding poorly to IGFBPs stimulate growth in the rat yet inhibit growth in the pig.[5] Guinea pig, neonatal pig, calf and cattle studies followed, each probing how the analog interacts with a species' own IGF and binding-protein system.[2][1][6]The gut became a second focus. A review of IGFs in small intestinal development summarized LR3-IGF-I as affecting the intestine much as IGF-1 does, but with higher potency.[7] The pepsin-resistance work was framed around potential oral applications for gastric growth and repair.[3]

## Mechanisms Studied in Research

The central mechanism studied is reduced capture by IGF binding proteins, which leaves more of the analog free to act on tissues. Several studies also tracked how the analog feeds back on the growth hormone and IGF axis.[2][5]
### Feedback on the GH-IGF axis
In finisher pigs, IGF-1 LR3 infusion cut mean plasma growth hormone by 23% and the area under growth hormone peaks by 60%, alongside lower IGFBP-3, IGF-1 and insulin. The authors proposed that suppressed growth hormone explained the drop in those downstream markers.[5] In guinea pigs and in neonatal pigs, the analog likewise lowered circulating IGF-1.[2][1]
### Glucose, amino acids and signaling
In beef heifers, the analog markedly reduced plasma concentrations of all amino acids measured and of glucose, and raised a 31-32 kDa binding protein, possibly IGFBP-1.[8] In prostate cancer cell lines, Long-R3 IGF-I produced a threefold increase in telomerase activity, similar to IGF-1, while the analog [Ala31,Leu60]IGF-I did not. Blocking Akt with wortmannin abolished the IGF effect; blocking MAPK did not.[9]

## Key Findings From Published Studies

Published studies show that IGF-1 LR3 is more potent than IGF-1 on several tissue measures, but its effect on whole-body growth depends heavily on species and context. All findings below come from animal or cell-culture models.
### Growth and organ weight

- Guinea pigs: a 7-day infusion increased the relative weight of the adrenals, gut, kidneys and spleen without improving body weight gain, feed intake or carcass composition, while plasma IGF-I, IGF-II and binding proteins fell.[2]
- Finisher pigs: a 4-day infusion decreased average daily gain and food intake, and co-administered porcine growth hormone did not reverse the effect.[5]
- Artificially reared neonatal pigs: no effect on daily gain in the first 9 days, but over a second 9-day period daily gain rose from 386 to 457 g/day with the analog, while native IGF-1 had no significant effect.[1]
### Intestine and metabolism

- Rat jejunum: Long-R3-IGF-I, but not IGF-1, raised uptake of the glucose analog 3-O-methyl-D-glucose per cm of jejunum by up to 69%; the gain disappeared when expressed per unit tissue weight, pointing to more mucosa rather than more transporters.[10]
- Beef heifers on restricted feed: intravenous infusion tended to conserve whole-body and skeletal muscle protein.[8]
- Neonatal calves: the analog lowered plasma glucose and insulin when given parenterally but had no effect when fed orally.[6]
- Dairy cows: intramammary infusion did not increase milk protein yield; milk, protein and fat yields were slightly lower, possibly linked to a rise in somatic cell count.[11]
### Cell culture
In LAPC-4, PC-3 and DU-145 prostate cancer cells, IGF-1 raised telomerase activity two- to tenfold and increased expression of the telomerase catalytic subunit hTERT. Long-R3 IGF-I produced a comparable threefold rise, placing the analog among the IGF peptides that can drive this pathway in vitro.[9]
### What the evidence does not show
None of these studies tested IGF-1 LR3 in controlled human trials, and the animal results do not point in one direction. Increased organ or mucosal mass often occurred without matching gains in whole-body growth or function, a gap the rat absorption study highlighted directly.[10][2]As a recombinant protein with no PubChem record, IGF-1 LR3 is typically verified by mass spectrometry and HPLC data on a certificate of analysis.

## Regulatory and Research Status

IGF-1 LR3 is not approved by the US Food and Drug Administration or other major regulators for any human use, and it has no established clinical record. It remains a laboratory reagent used in cell biology and animal research.The only recombinant IGF-1 product approved in the United States is mecasermin, a version of native human IGF-1, which is distinct from the LR3 analog. Growth factors including IGF-1 and its analogs are prohibited in sport under the World Anti-Doping Agency's Prohibited List.A 2010 case report found His-tagged Long-R3-IGF-I, a form usually produced for biochemical studies, in a vial obtained from the black market. The authors noted that the effects of this tagged protein in humans have not been described and that it was likely a by-product of laboratory work rather than material made for human use.[4]

## FAQ

**What is IGF-1 LR3?**
IGF-1 LR3, or Long R3 IGF-1, is a recombinant analog of insulin-like growth factor 1. It adds an N-terminal extension peptide and places an arginine at position 3, changes that greatly reduce binding to IGF binding proteins. In rat studies it was more potent than native IGF-1. Nearly all published research on it involves animals or cell culture.

**How is IGF-1 LR3 different from IGF-1?**
IGF-1 LR3 differs from native IGF-1 by its N-terminal extension and arginine substitution. The practical result is much lower affinity for IGF binding proteins. Animal studies found it more potent than IGF-1 on measures such as intestinal glucose uptake and organ weight, and in neonatal pigs it raised daily weight gain where IGF-1 did not.

**Is IGF-1 LR3 the same as IGF-1 DES?**
No. Both are IGF-1 analogs with reduced binding-protein affinity, but they are built differently. IGF-1 LR3 is a longer molecule with an added N-terminal extension and an arginine at position 3. IGF-1 DES (1-3) is a shorter, truncated form that lacks the first three amino acids of native IGF-1.

**What is the molecular weight of IGF-1 LR3?**
PubChem has no compound record for IGF-1 LR3, so this page does not list a verified formula or molecular weight. It is a recombinant protein larger than native IGF-1 because of its N-terminal extension. Laboratories confirm its identity with high-resolution mass spectrometry of the intact and digested protein, as in a published anti-doping case report.

**Is IGF-1 LR3 FDA approved?**
No. IGF-1 LR3 is not FDA approved for any human use and has no published controlled human trials among the studies reviewed here. The approved recombinant IGF-1 drug in the United States is mecasermin, which matches native human IGF-1. IGF-1 analogs are also prohibited in sport by the World Anti-Doping Agency.

**What does the research on IGF-1 LR3 show?**
Animal research shows species-dependent effects. In guinea pigs it enlarged the gut, kidneys, spleen and adrenals without increasing body growth. In finisher pigs it reduced growth and suppressed growth hormone, while in neonatal pigs it increased daily gain later in the study. In rats it increased intestinal glucose uptake by enlarging the mucosa.

## References

1. Dunshea FR, Chung CS, Owens PC, et al. Insulin-like growth factor-I and analogues increase growth in artificially-reared neonatal pigs. The British journal of nutrition 2002. PMID: 12067429
2. Conlon MA, Tomas FM, Owens PC, et al. Long R3 insulin-like growth factor-I (IGF-I) infusion stimulates organ growth but reduces plasma IGF-I, IGF-II and IGF binding protein concentrations in the guinea pig. The Journal of endocrinology 1995. PMID: 7561636
3. Bryant KJ, Read LC, Forsberg G, et al. Design and characterisation of long-R3-insulin-like growth factor-I muteins which show resistance to pepsin digestion. Growth factors (Chur, Switzerland) 1996. PMID: 8919033
4. Kohler M, Thomas A, Walpurgis K, et al. Detection of His-tagged Long-R³-IGF-I in a black market product. Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society 2010. PMID: 20675162
5. Dunaiski V, Dunshea FR, Walton PE, et al. Long [R3] insulin-like growth factor-I reduces growth, plasma growth hormone, IGF binding protein-3 and endogenous IGF-I concentrations in pigs. The Journal of endocrinology 1997. PMID: 9488001
6. Hammon H, Blum JW. Endocrine and metabolic changes in neonatal calves in response to growth hormone and long-R3-insulin-like growth factor-I administration. Biology of the neonate 1998. PMID: 9483305
7. MacDonald RS. The role of insulin-like growth factors in small intestinal cell growth and development. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 1999. PMID: 10226789
8. Hill RA, Hunter RA, Lindsay DB, et al. Action of long(R3)-insulin-like growth factor-1 on protein metabolism in beef heifers. Domestic animal endocrinology 1999. PMID: 10370861
9. Wetterau LA, Francis MJ, Ma L, et al. Insulin-like growth factor I stimulates telomerase activity in prostate cancer cells. The Journal of clinical endocrinology and metabolism 2003. PMID: 12843187
10. Garnaut SM, Howarth GS, Read LC. Effects of insulin-like growth factor-I and its analogue, long-R3-IGF-I, on intestinal absorption of 3-O-methyl-D-glucose are less pronounced than gut mucosal growth responses. Growth factors (Chur, Switzerland) 2002. PMID: 11999215
11. Mackle TR, Dwyer DA, Bauman DE. Intramammary infusion of insulin or long R3 insulin-like growth factor-I did not increase milk protein yield in dairy cows. Journal of dairy science 2000. PMID: 10984150