IGF-1 LR3: Research, Handling and Batch Documentation

Identity and research status

Also referred to as

Long R3 IGF-1, Long Arg3 Insulin-like Growth Factor-1

Sequence

MFPAMPLSSL FVNGPRTLCG AELVDALQFV CGDRGFYFNK PTGYGSSSRR APQTGIVDEC CFRSCDLRRL EMYCAPLKPA KSA

Sequence Length

83 residues (70-residue mature IGF-1 plus a 13-residue N-terminal extension)

Modifications

Arg substituted for Glu at position 3 of the IGF-1 sequence; N-terminal extension Met-Phe-Pro-Ala-Met-Pro-Leu-Ser-Ser-Leu-Phe-Val-Asn

Molecular Formula

C400H619N111O115S9 (folded, three disulfide bonds); C400H625N111O115S9 for the reduced chain

Molecular Weight

9,111.5 g/mol folded; 9,117.6 g/mol calculated for the reduced chain

Disulfide Bonds

Three, at the positions corresponding to Cys6-Cys48, Cys18-Cys61 and Cys47-Cys52 of mature IGF-1

CAS Number

946870-92-4

Parent Protein

Human IGF-1, UniProt P05019, mature chain residues 49 to 118

Molecular Class

Recombinant protein, expressed in Escherichia coli as an N-terminally extended fusion and refolded in vitro

Native Counterpart

Mature human IGF-1, 70 residues, 7,648.7 g/mol folded

Mechanism, in brief

The primary target is the type 1 IGF receptor (IGF-1R), a disulfide-linked alpha2beta2 receptor tyrosine kinase. Ligand occupancy of the extracellular alpha subunits drives trans-autophosphorylation of the beta-subunit kinase domain, which then recruits insulin receptor substrate 1 and 2 and the adaptor Shc. Two branches follow. The PI3K/Akt arm raises protein synthesis through mTORC1 and S6K1, suppresses FoxO-driven transcription of the muscle atrophy genes, and phosphorylates Bad to blunt apoptosis. The Ras/Raf/MEK/ERK arm carries the proliferative signal and cell cycle entry.

1. Binding protein escape. Arg at position 3 and the hydrophobic N-terminal extension both disrupt the IGFBP contact surface, so the analogue is not sequestered into the IGFBP-3 and acid-labile subunit ternary complex that holds most native IGF-1 out of circulation as free ligand.
2. IGF-1R occupancy. Free analogue binds the alpha subunits of the alpha2beta2 IGF-1 receptor with roughly threefold lower affinity than native IGF-1, which is more than offset by the much larger free fraction in any medium containing binding proteins.
3. Kinase activation and substrate docking. Occupancy triggers trans-autophosphorylation of the beta-subunit tyrosine kinase, creating docking sites for IRS-1, IRS-2 and Shc.
4. PI3K and Akt arm. IRS-bound PI3K generates PIP3, activating Akt, which drives mTORC1 and S6K1 to raise translation initiation, phosphorylates and excludes FoxO transcription factors, and phosphorylates Bad to reduce apoptotic signalling.
5. Ras and MAPK arm. Shc and Grb2 route the signal through Ras, Raf, MEK and ERK1/2, which carries the proliferative and cell cycle entry component observed in myoblast and fibroblast cultures.
6. Feedback onto the somatotropic axis. In whole animals the signal feeds back on growth hormone secretion. A four-day infusion in finisher pigs cut mean plasma growth hormone by 23 percent and the area under the growth hormone pulse curve by 60 percent, with plasma IGFBP-3, endogenous IGF-1 and insulin all falling alongside it.

The full research write-up, including the findings behind each claim and the model each came from, is on the IGF-1 LR3 1mg 1mg page.

Vial sizes available

Every size of IGF-1 LR3 Volta lists, in stock or not. Each is a separate catalogue page with its own batch number and specification table.

• IGF-1 LR3 1mg 1mgBatch #: VPIG1100
  Restocking

Purity and batch documentation

Volta's release specification is >99% (HPLC). That is a threshold we set. >99% is the specification every batch is released to. The figure on a certificate is what a laboratory measured for one lot.

No third-party certificate has been published for IGF-1 LR3yet. The certificates Volta does publish, with the laboratory's own verification link on each, are in the certificate archive.

Research on IGF-1 LR3

Handling and stability

Regulatory context

United States

Not FDA-approved. Research chemical only. WADA-banned (S2 growth factors).

Canada

Not approved.

United Kingdom

Not approved.

• the legal status of research peptides in Canada
• Health Canada's regulatory position

Primary sources

1. 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, following their expression in Escherichia coli as fusion proteins. Journal of Molecular Endocrinology (1992). doi:10.1677/jme.0.0080029
2. 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. Journal of Molecular Endocrinology (1992). doi:10.1677/jme.0.0080213
3. Tomas FM, Knowles SE, Owens PC, et al.. Insulin-like growth factor-I (IGF-I) and especially IGF-I variants are anabolic in dexamethasone-treated rats. Biochemical Journal (1992). doi:10.1042/bj2820091
4. Read LC, Tomas FM, Howarth GS, et al.. Insulin-like growth factor-I and its N-terminal modified analogues induce marked gut growth in dexamethasone-treated rats. Journal of Endocrinology (1992). doi:10.1677/joe.0.1330421
5. Tomas FM. The anti-catabolic efficacy of insulin-like growth factor-I is enhanced by its early administration to rats receiving dexamethasone. Journal of Endocrinology (1998). doi:10.1677/joe.0.1570089
6. Dunaiski V, Dunshea FR, Walton PE, Goddard C. Long [R3] insulin-like growth factor-I reduces growth, plasma growth hormone, IGF binding protein-3 and endogenous IGF-I concentrations in pigs. Journal of Endocrinology (1997). doi:10.1677/joe.0.1550559
7. Morris AE, Schmid J. Effects of insulin and LongR(3) on serum-free Chinese hamster ovary cell cultures expressing two recombinant proteins. Biotechnology Progress (2000). doi:10.1021/bp0000914
8. Becker J, Timmermann C, Rupp O, et al.. Transcriptome analyses of CHO cells with the next-generation microarray CHO41K: development and validation by analysing the influence of the growth stimulating substance IGF-1 substitute LongR(3). Journal of Biotechnology (2014). doi:10.1016/j.jbiotec.2014.02.021
9. Qian Y, Lewis AM, Sidnam SM, et al.. LongR3 enhances Fc-fusion protein N-linked glycosylation while improving protein productivity in an industrial CHO cell line. Process Biochemistry (2017). doi:10.1016/j.procbio.2016.11.018
10. Bieberich E. Replacement of insulin by LongR3-IGF-1 allows for the differentiation of ES cells into neuroprogenitors and insulin-secreting cells. Analytical Biochemistry (2005). doi:10.1016/j.ab.2005.07.042
11. Araujo MS, Guastali MD, Paulini F, et al.. Molecular and cellular effects of insulin-like growth factor-1 and LongR3-IGF-1 on in vitro maturation of bovine oocytes: comparative study. Growth Hormone & IGF Research (2020). doi:10.1016/j.ghir.2020.101357
12. Lu Z, Liu N, Huang H, et al.. Recombinant expression of IGF-1 and LR3 IGF-1 fused with xylanase in Pichia pastoris. Applied Microbiology and Biotechnology (2023). doi:10.1007/s00253-023-12606-0
13. Stremming J, Heard S, White A, et al.. IGF-1 infusion to fetal sheep increases organ growth but not by stimulating nutrient transfer to the fetus. American Journal of Physiology: Endocrinology and Metabolism (2021). doi:10.1152/ajpendo.00453.2020
14. White A, Stremming J, Brown LD, Rozance PJ. Attenuated glucose-stimulated insulin secretion during an acute IGF-1 LR3 infusion into fetal sheep does not persist in isolated islets. Journal of Developmental Origins of Health and Disease (2023). doi:10.1017/S2040174423000090
15. White A, Stremming J, Wesolowski SR, et al.. IGF-1 LR3 does not promote growth in late-gestation growth-restricted fetal sheep. American Journal of Physiology: Endocrinology and Metabolism (2025). doi:10.1152/ajpendo.00259.2024
16. Mongongu C, Coudore F, Domergue V, et al.. Detection of LongR3-IGF-I, Des(1-3)-IGF-I, and R3-IGF-I using immunopurification and high resolution mass spectrometry for antidoping purposes. Drug Testing and Analysis (2021). doi:10.1002/dta.3016
17. 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 (2010). doi:10.1016/j.ghir.2010.07.001
18. Firth SM, McDougall F, McLachlan AJ, Baxter RC. Impaired blockade of insulin-like growth factor I (IGF-I)-induced hypoglycemia by IGF binding protein-3 analog with reduced ternary complex-forming ability. Endocrinology (2002). doi:10.1210/endo.143.5.8764
19. Engel MG, Narayan S, Cui MH, et al.. 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. Journal of Alzheimer's Disease (2025). doi:10.1177/13872877241299056
20. Yavuz E, Sagir MS, Ercan A, et al.. Decellularized Alstroemeria stem-based nerve conduit integrated with GelMA and controlled IGF-1 LR3 release for enhanced rat sciatic nerve regeneration. International Journal of Biological Macromolecules (2025). doi:10.1016/j.ijbiomac.2025.147888
21. UniProt Consortium. UniProtKB P05019 (IGF1_HUMAN): Insulin-like growth factor I, Homo sapiens. UniProt Knowledgebase (2026)