F tier · safety concern
There is not one human clinical trial of IGF-1 LR3 for any indication; the molecule was deliberately engineered to escape the IGF-binding-protein system that normally restrains IGF-1 receptor signalling, it is sold and validated by its manufacturers as a cell-culture reagent whose bioassay is breast cancer cell proliferation, and the epidemiology of the pathway it maximally activates links higher IGF-I to elevated cancer risk.
igf-1 lr3
IGF-1 LR3 is an 83-residue recombinant analogue of human IGF-1 carrying a Glu3-to-Arg substitution and a 13-residue N-terminal extension, modifications that give it markedly reduced affinity for IGF-binding proteins and therefore greater free access to the IGF-1 receptor. Its documented use is as a serum-free supplement in mammalian cell culture and bioprocessing; there are no published human clinical trials, and animal studies show it can suppress endogenous GH and IGF-1 and impair beta-cell insulin secretion.
// we supply this one
available as a research reagent
≥ 95% (SDS-PAGE / HPLC) · lyophilised powder · batch certificate published. Grade F above is our own and is not adjusted because we stock it.
the explanation
IGF-1 LR3 is a lab-made version of IGF-1 rebuilt so the body's natural braking system cannot hold onto it, which means it hits its receptor much harder and for longer. It has never been tested in a human trial for anything — its actual job is feeding cells in a bioreactor, and one of the standard tests suppliers use to prove it works is making breast cancer cells multiply.
regulatory status
Not approved for human use anywhere; marketed and labelled 'For research use only'
Supplied by protein manufacturers as a cell-culture reagent with an explicit research-use-only notice and no human therapeutic authorisation, and prohibited at all times in sport under WADA S2.3, which covers 'Insulin-like growth factor 1 (IGF-1, mecasermin) and its analogues'.
how it works · proposed mechanism
Every property that makes IGF-1 LR3 attractive to users is the same property that makes it a poor candidate for human exposure: it was built to defeat physiological regulation.
Engineered to evade IGFBPs
The Arg-for-Glu substitution at position 3 plus a 13-residue N-terminal extension drop the molecule's affinity for IGF-binding proteins far below that of native IGF-1. In vivo, more than 99% of circulating IGF-1 is normally sequestered in IGFBP complexes, so removing that sequestration is a large change in effective receptor exposure.
Maximal IGF-1R signalling
With the binding-protein buffer removed, the analogue drives PI3K/Akt and MAPK signalling downstream of IGF-1R more freely than native IGF-1. Its standard potency bioassay is proliferation of MCF-7 human breast cancer cells in serum-free medium — mitogenicity is the validated readout, not a side effect.
Negative feedback on the GH axis
IGF-1 exerts negative feedback on pituitary GH release. In pigs, LR3 IGF-I at 180 µg/kg/day decreased average daily gain and reduced plasma GH, IGFBP-3 and endogenous IGF-I, meaning exogenous analogue partially replaced rather than added to the animal's own axis.
Beta-cell consequences
A one-week IGF-1 LR3 infusion in late-gestation fetal sheep reduced glucose-stimulated insulin secretion, and the defect persisted in islets isolated from those animals — evidence of an intrinsic islet lesion rather than a transient systemic effect.
what’s reported
evidence shape
6 sourcesThe composition of the cited literature by study type. This describes the shape of the evidence, not its quality — and it does not by itself set the grade.
⚠ the catch
Pooled individual participant data from 19 studies covering 10,554 prostate cancer cases and 13,618 controls found that men in the highest fifth of circulating IGF-I had an odds ratio of 1.29 (95% CI 1.16-1.43) versus the lowest fifth — and IGF-1 LR3 is specifically designed to push free IGF-1 receptor signalling higher than endogenous IGF-1 physiologically can. Deliberately maximising the exact axis that observational oncology has repeatedly flagged, with zero human trial data and a supply chain in which a seized vial was found to contain a His-tagged biochemical-research variant, is the definition of an F.
key published findings
- Human epidemiology (Travis 2016, Cancer Research, pooled individual participant data from 17 prospective and 2 cross-sectional studies, up to 10,554 prostate cancer cases and 13,618 controls): odds ratio 1.29 (95% CI 1.16-1.43) for prostate cancer comparing highest versus lowest fifth of circulating IGF-I — an association with endogenous IGF-I, and the strongest available human-relevant signal for a compound that maximises IGF-1R signalling.
- Manufacturer specification (R&D Systems / Bio-Techne LR3 IGF-I, catalogue 8335-G1): Gly49-Ala118 with Glu51Arg plus a 13-amino-acid N-terminal extension from methionyl porcine growth hormone, observed mass 9,112 Da, 'considerably lower affinity binding to IGFBPs compared to wild-type IGF-I', bioactivity validated by proliferation of MCF-7 human breast cancer cells, labelled 'For research use only'.
- Livestock study (Dunaiski 1997, J Endocrinol, pigs, 180 µg/kg/day): Long [R3] IGF-I decreased average daily gain and reduced plasma growth hormone, IGFBP-3 and endogenous IGF-I concentrations — the analogue suppressed the animals' own somatotropic axis and impaired rather than improved growth.
- Fetal sheep study (White 2021, Am J Physiol Endocrinol Metab, 1-week IGF-1 LR3 infusion in late gestation): treated fetuses had lower insulin secretion than controls, and the impairment persisted in isolated islets, demonstrating 'an intrinsic islet defect in insulin release when exposed to IGF-1 LR3 infusion for 1 wk'.
- Forensic (Kohler 2010, Growth Horm IGF Res): a black-market injection vial seized from an athlete was found by mass spectrometry to contain His-tagged Long-R3-IGF-I — a hexahistidine-tagged construct made for biochemical studies, with the authors noting the effects of the tagged variant in humans are undocumented.
limitations of the evidence
- No human pharmacokinetic study exists; the widely repeated '20-30 hour half-life' figure has no identifiable primary human source, and on first principles reduced IGFBP binding would be expected to shorten rather than lengthen circulating persistence relative to complexed native IGF-1.
- The cancer-risk evidence is observational and concerns endogenous circulating IGF-I, not administered IGF-1 LR3 — it establishes a hazard for the pathway rather than a measured risk for the compound, because no such measurement exists.
- Animal findings are heterogeneous across species and developmental stages (guinea pig, pig, sheep, calf, mouse) and were mostly designed to answer agricultural or developmental-physiology questions, not to model adult human exposure.
- Product identity cannot be verified in unregulated supply: at least one seized preparation contained a His-tagged research construct rather than the untagged analogue.
documented safety signals
- Circulating IGF-I in the highest versus lowest fifth is associated with a 29% higher odds of prostate cancer in the largest pooled individual-participant analysis available; the compound is engineered to raise free IGF-1R signalling beyond physiological range.
- Mitogenicity is the manufacturer's validated potency assay, using proliferation of human breast cancer cells.
- Demonstrated intrinsic beta-cell defect with reduced glucose-stimulated insulin secretion after one week of exposure in fetal sheep; hypoglycaemia is a recognised class effect of IGF-1 receptor agonism.
- Suppression of endogenous growth hormone, IGF-1 and IGFBP-3 with impaired growth in pigs at 180 µg/kg/day — the axis is downregulated, not augmented.
- Documented supply-chain contamination with a hexahistidine-tagged research construct of unknown human immunogenicity.
identity
| full name | Long R3 Insulin-like Growth Factor-1 (LONG R3 IGF-I) |
| category | Growth Hormone |
| modality | protein hormone |
| molar mass | 9112 g/mol |
| cas | 946870-92-4 |
laboratory handling
| storage | Lyophilised protein is stored at -20 °C to -80 °C, desiccated and protected from light; reconstituted solution is used within a short window at 2-8 °C or aliquoted and stored at -20 °C to -80 °C, and repeated freeze-thaw cycles are avoided because the folded three-disulfide protein is prone to aggregation and loss of activity. |
| solubility | Reconstituted in sterile water, or in dilute acid such as 10 mM HCl or dilute acetic acid where a stock above about 100 µg/mL is required, then diluted into buffer; carrier protein is often added in cell-culture use to reduce adsorption losses. |
Handling information describes laboratory practice for a research reagent. It is not a preparation guide for use in humans.
the receipts
6 citedR&D Systems / Bio-Techne · 2024 · official
World Anti-Doping Agency · 2026 · official
Cancer Research · 2016 · peer-reviewed
Growth Hormone & IGF Research · 2010 · peer-reviewed
Journal of Endocrinology · 1997 · preclinical
American Journal of Physiology - Endocrinology and Metabolism · 2021 · preclinical
others in Growth Hormone