IGF-1 LR3 Half-Life: ~20–30 Hours
Long-arginine-3 IGF-1 analogue · ~100× reduced IGFBP binding · Animal data only · Not FDA-approved · WADA S2 Prohibited
⚠ Animal Study Not FDA-Approved WADA S2 ProhibitedQuick Reference
| Parameter | Value | Notes |
|---|---|---|
| Plasma half-life | ~20–30 hours | Animal studies only; no human PK data[1] |
| Native IGF-1 t½ (free) | ~10 minutes | Rapid clearance via IGFBP binding |
| IGFBP binding reduction | ~100-fold | Arg3 substitution + N-terminal extension[1] |
| Route | SC injection | Research use only |
| Molecular weight | ~9,200 Da | vs ~7,647 Da for native IGF-1 |
| FDA approval | None | Research compound only |
| WADA status | Prohibited S2 | In- and out-of-competition |
| Data Quality | ⚠ Animal Study — No controlled human pharmacokinetic data exists for IGF-1 LR3 | |
Why IGF-1 LR3 Has a 100× Longer Half-Life
Native IGF-1 circulates primarily in large ternary complexes with IGFBP-3 and the acid-labile subunit (ALS). Free (unbound) IGF-1 has a plasma half-life of only approximately 10 minutes due to rapid receptor binding and IGFBP sequestration.[2]
IGF-1 LR3 (Long-arginine-3 IGF-1) was engineered with two key structural modifications that dramatically reduce IGFBP binding affinity:[1]
Structural Modifications
| Feature | Native IGF-1 | IGF-1 LR3 | Effect |
|---|---|---|---|
| Length | 70 amino acids | 83 amino acids | +13 AA N-terminal extension |
| Position 3 | Glutamic acid (Glu) | Arginine (Arg) | Disrupts IGFBP-3 binding domain |
| IGFBP affinity | High (normal) | ~100× reduced[1] | Predominantly free in circulation |
| IGF1R binding | High | Comparable to native[1] | Receptor signaling preserved |
| Plasma half-life | ~10 min (free) | ~20–30 h (animal) | ~100–180× longer |
By evading IGFBP sequestration, IGF-1 LR3 circulates predominantly in free, receptor-accessible form. Francis et al. (1992) demonstrated this markedly reduced binding affinity and extended biological activity in animal receptor assays.[1]
Pharmacokinetics: What Animal Data Shows
Estimated Half-Life vs Native IGF-1
| Compound | Half-Life | Data Source | IGFBP Binding |
|---|---|---|---|
| Free native IGF-1 | ~10 minutes | Human studies[2] | Normal (high) |
| IGFBP-3-bound IGF-1 | ~12–15 hours | Human studies[2] | N/A (sequestered) |
| Mecasermin SC (Increlex) | ~5.8 hours | Human PK trial[3] | Normal (endogenous complex) |
| IGF-1 LR3 | ~20–30 hours | Animal studies only[1] | ~100× reduced |
Estimated Clearance Timeline (Animal-Derived, t½ = 25 h)
Using a midpoint estimate of 25 hours. These values are extrapolated from animal data and have not been validated in humans.
| Half-Lives Elapsed | Approximate Time | % Remaining (theoretical) |
|---|---|---|
| 1 t½ | ~25 hours | 50% |
| 2 t½ | ~50 hours | 25% |
| 3 t½ | ~75 hours (~3 days) | 12.5% |
| 4 t½ | ~100 hours (~4 days) | 6.25% |
| 5 t½ | ~125 hours (~5 days) | <3.1% (effectively cleared) |
Regulatory and WADA Status
IGF-1 LR3 has never received approval from the FDA, EMA, or any major regulatory authority for human use. It is classified as a research chemical.
Under the World Anti-Doping Agency (WADA) Prohibited List, IGF-1 LR3 is explicitly prohibited under Section S2 (Peptide Hormones, Growth Factors, Related Substances and Mimetics), both in-competition and out-of-competition.[4] The prohibition covers all IGF-1 analogues with modified receptor-binding or binding-protein characteristics.
Regulatory Comparison
| Compound | FDA Status | WADA Status | Human PK Data |
|---|---|---|---|
| IGF-1 (mecasermin) | Approved (NDA 021839) | Prohibited S2 | Yes (RCT) |
| IGF-1 LR3 | Not approved | Prohibited S2 | None published |
| HGH (somatropin) | Approved (NDA 020280) | Prohibited S2 | Yes (RCT) |
Track Peptide Timing Precisely
Halflife Labs calculates clearance curves from injection time. Built for research protocols — log IGF-1 LR3, peptides, and other compounds with timing data.
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Despite its structural modifications, IGF-1 LR3 retains the ability to bind the IGF-1 receptor (IGF1R) with potency comparable to native IGF-1. The key binding domain of IGF-1 (the B and D regions) is preserved in the LR3 variant.[1]
Downstream signaling proceeds through the same pathways as native IGF-1:
- PI3K → Akt → mTOR pathway (protein synthesis, cell survival)
- MAPK/ERK pathway (cell proliferation)
- IRS-1 phosphorylation (metabolic effects)
Because IGF-1 LR3 circulates predominantly free (unbound to IGFBPs), a greater proportion of the molecule is receptor-accessible at any given time compared to native IGF-1, where approximately 99% is IGFBP-bound at steady state.[2]
IGF-1 Analogue and Related Compound Comparison
| Compound | Half-Life | IGFBP Binding | Approval | Data Grade |
|---|---|---|---|---|
| IGF-1 (mecasermin) | ~5.8 h SC | Normal | FDA (NDA 021839) | Human PK Study |
| IGF-1 LR3 | ~20–30 h (animal) | ~100× reduced | None | Animal Study only |
| HGH (somatropin) | ~3–4 h SC | N/A | FDA (NDA 020280) | Human RCT |
Frequently Asked Questions
What is the half-life of IGF-1 LR3?
Based on animal studies, IGF-1 LR3 has a plasma half-life of approximately 20–30 hours, compared to approximately 10 minutes for free native IGF-1. This extended half-life results from the molecule's ~100-fold reduced affinity for IGFBPs. No controlled human pharmacokinetic studies exist for IGF-1 LR3.
Why does IGF-1 LR3 have a longer half-life than regular IGF-1?
IGF-1 LR3 has a 13-amino acid N-terminal extension and an arginine substitution at position 3. These modifications reduce IGFBP binding affinity by ~100-fold. Since IGFBPs normally sequester and rapidly clear IGF-1, evading IGFBP binding keeps IGF-1 LR3 in free, active form far longer than native IGF-1.[1]
Is IGF-1 LR3 FDA-approved?
No. IGF-1 LR3 has never received FDA approval for any human indication. It is a research-grade peptide. The FDA-approved form of IGF-1 for human use is mecasermin (Increlex, NDA 021839), which uses recombinant native IGF-1, not the LR3 analogue.
Is IGF-1 LR3 on the WADA prohibited list?
Yes. IGF-1 LR3 is prohibited in-competition and out-of-competition under WADA Prohibited List category S2 (Peptide Hormones, Growth Factors, Related Substances and Mimetics). All IGF-1 analogues including LR3 are explicitly prohibited.[4]
What data exists for IGF-1 LR3 in humans?
There are no published, peer-reviewed controlled pharmacokinetic or pharmacodynamic studies of IGF-1 LR3 in humans. Available data comes from in vitro receptor binding assays and in vivo animal studies. The 20–30 hour half-life estimate is extrapolated from animal data and should not be assumed to apply directly to human physiology.[1]
How does IGF-1 LR3 compare to mecasermin (Increlex)?
Mecasermin (Increlex) is FDA-approved recombinant native IGF-1 with a subcutaneous half-life of ~5.8 hours in humans from controlled trials.[3] IGF-1 LR3 has an estimated half-life of ~20–30 hours from animal studies only, no FDA approval, and no human PK data. Mecasermin's safety profile is established; IGF-1 LR3's human safety profile is unknown.
Does IGF-1 LR3 bind to the IGF-1 receptor?
Yes. Despite its structural modifications, IGF-1 LR3 retains binding to the IGF-1 receptor (IGF1R) and stimulates downstream PI3K/Akt and MAPK/ERK signaling. Its reduced IGFBP binding means a greater proportion circulates in free, receptor-accessible form. In vitro studies confirm receptor binding potency comparable to native IGF-1.[1]
What is the difference between IGF-1 LR3 and native IGF-1?
Native IGF-1 (70 amino acids) has a free plasma half-life of ~10 minutes and is ~99% IGFBP-bound at steady state. IGF-1 LR3 adds a 13-amino acid N-terminal extension and substitutes arginine at position 3, reducing IGFBP binding ~100-fold and extending estimated half-life to ~20–30 hours in animal models.[1] Unlike native IGF-1, LR3 is not approved for human use.
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Get the App (iOS)References
- 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;8(3):213–223. PMID: 1390830
- Guler HP, Zapf J, Froesch ER. Short-term metabolic effects of recombinant human insulin-like growth factor I in healthy adults. N Engl J Med. 1987;317(3):137–140. PMID: 3298643
- Guevara-Aguirre J, Rosenbloom AL, Vasconez O, et al. Two-year treatment of growth hormone (GH) receptor deficiency with recombinant insulin-like growth factor I in 22 children: comparison of two dosage levels and to GH-treated GH deficiency. J Clin Endocrinol Metab. 1997;82(2):629–633. PMID: 9024264
- World Anti-Doping Agency. Prohibited List 2024: Section S2 — Peptide Hormones, Growth Factors, Related Substances and Mimetics. WADA; 2024. Available at: wada-ama.org
- Buckway CK, Wilson EM, Ahlsén M, et al. Insulin-like growth factor binding protein-3 as a surrogate measure of serum IGF-I bioactivity: studies with a growth hormone receptor antagonist. J Clin Endocrinol Metab. 1999;84(5):1670–1676. PMID: 10323394