Educational reference, not medical advice. This page summarizes information from published research and regulatory filings for educational purposes. It is not a recommendation to use any compound and should not replace guidance from a licensed healthcare provider. Most peptides discussed here are not approved for the uses described.
What it is
IGF-1 LR3, or Long R3 IGF-1, is a 83-amino-acid recombinant analog of human insulin-like growth factor-1. It differs from native IGF-1 in two ways: an arginine substitution at position 3 (the "R3" in the name) that disrupts binding to the family of IGF-binding proteins (IGFBPs), and a 13-amino-acid N-terminal extension borrowed from methionyl porcine growth hormone. The combined effect is a molecule that circulates with a far longer functional half-life than native IGF-1 because it spends less time sequestered by IGFBP-3.
The analog was developed by GroPep, a spin-out from the Australian CSIRO, primarily as a serum-free supplement for mammalian cell culture. It is sold for that purpose under the trade name LONG R3 IGF-I and remains a workhorse reagent in bioprocessing and stem-cell research.
History
The molecule was first described in a series of papers from Francis, Ballard, and colleagues at the CSIRO between 1989 and 1992. The Tomas et al. 1991 paper in Biochemical Journal established that Long-R3-IGF-I given to diabetic rats produced larger gains in muscle protein synthesis and nitrogen retention than recombinant native IGF-1 at the same dose — a finding the authors attributed directly to the analog's ability to evade IGFBPs.
GroPep filed early patents covering the production process and licensed the analog for industrial cell culture, where it replaces insulin in many feed formulations. There has never been a human therapeutic development program for IGF-1 LR3, and it has not been the subject of a published Phase I or Phase II trial in humans.
Regulatory status
IGF-1 LR3 has no approved medical use. It is sold globally as a research and cell-culture reagent under not-for-human-use labeling. The World Anti-Doping Agency lists IGF-1 and its analogs under category S2 of the Prohibited List, banning their use in competitive sport at all times. In the United States the FDA has not approved IGF-1 LR3 for any indication; in 2023 it was placed in Category 2 of the 503A bulk substances list, restricting compounding for patient use.
Sales to consumers occur almost exclusively through research-chemical suppliers, and shipments are routinely seized at the U.S. border when labeled for human use.
How researchers describe its action
IGF-1 LR3 binds the same type-1 IGF receptor (IGF-1R) as native IGF-1, with similar receptor affinity. The mechanistic point of interest is what happens before it reaches the receptor: native IGF-1 in circulation is more than 99% bound to IGFBP-3 in a ternary complex with the acid-labile subunit, which acts as a slow-release reservoir. The R3 substitution reduces IGFBP affinity by roughly two orders of magnitude, leaving more free analog available to engage the receptor. The N-terminal extension is generally considered to slow proteolytic clearance.
Downstream of IGF-1R, the analog activates the same PI3K/Akt and MAPK pathways as native IGF-1, driving cell proliferation, protein synthesis, and inhibition of apoptosis. In skeletal muscle cell cultures these pathways converge on mTOR activation.
Half-life and dosing intervals
The published half-life of IGF-1 LR3 in rodents is roughly 20 to 30 hours, compared with about 10 to 12 minutes for free native IGF-1. This is the key pharmacokinetic difference and the basis for once-daily dosing in research protocols.
In animal studies, common research doses range from about 20 to 100 micrograms per kilogram per day administered subcutaneously. There is no established human dose. The doses commonly described in observational reports (typically 20 to 50 mcg once daily) are extrapolations from rodent data, not from controlled trials.
Reconstitution example
IGF-1 LR3 is supplied as a lyophilized powder, most often in 1 mg vials. A common reconstitution is 1 mL of bacteriostatic water added to a 1 mg vial, yielding 1 mg/mL — meaning 0.02 mL on a 1 mL insulin syringe (2 units on a U-100 syringe) contains 20 mcg, and 5 units contains 50 mcg. Vial's calculator handles the unit-to-mcg conversion automatically when you enter the vial mass and water volume.
What to know
- No human therapeutic data. Almost all efficacy evidence is from rodents or cell culture. No Phase II human trial has been published.
- Banned in sport. WADA prohibits IGF-1 LR3 and other IGF-1 analogs in and out of competition under S2.
- Hypoglycemia risk. Because IGF-1R shares signaling with the insulin receptor, IGF-1 analogs can lower blood glucose, particularly at higher doses or when combined with insulin.
- Storage. Lyophilized IGF-1 LR3 is stable refrigerated and is most stable frozen for long-term storage. Once reconstituted, refrigerate and use within the stability window quoted by the supplier (typically 2 to 4 weeks).
- Reported adverse effects in informal use include hypoglycemia, injection-site reactions, and water retention. Long-term safety, including theoretical concerns about cancer risk from sustained IGF-1R activation, has not been characterized in any controlled human study.
Sources
- 1.Francis GL, Ross M, Ballard FJ, Milner SJ, Senn C, McNeil KA, Wallace JC, King R, Wells JR (1992). 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.
- 2.Tomas FM, Knowles SE, Owens PC, Read LC, Chandler CS, Gargosky SE, Ballard FJ (1991). Increased weight gain, nitrogen retention and muscle protein synthesis following treatment of diabetic rats with insulin-like growth factor (IGF)-I and Long-R3-IGF-I. Biochemical Journal.
- 3.Ballard FJ, Wallace JC, Francis GL, Read LC, Tomas FM (1996). Des(1-3)IGF-I: a truncated form of insulin-like growth factor-I. International Journal of Biochemistry & Cell Biology.
- 4.World Anti-Doping Agency — Prohibited List, S2 Peptide Hormones, Growth Factors, Related Substances and Mimetics.