IGF-1 LR3 and IGF-1 DES are two forms of insulin-like growth factor-1 (IGF-1) that solve the same problem in different ways. Native IGF-1 is mostly held by IGF-binding proteins (IGFBPs), which limits how much reaches the receptor. IGF-1 DES is a natural form that is missing its first three amino acids. IGF-1 LR3 is an engineered form that adds a 13-residue extension and swaps one amino acid. Both bind IGFBPs weakly while still activating the IGF-1 receptor. This guide compares them side by side and links to the full research overview for each.
All compounds discussed are sold for laboratory research use only. This page summarizes published research and is not guidance for human or veterinary use.
At a glance
| IGF-1 LR3 | IGF-1 DES | |
|---|---|---|
| Also called | Long R3 IGF-1 | des(1-3)IGF-1 |
| Origin | Engineered by an Australian group in the early 1990s | Found in nature, first isolated from bovine colostrum and also identified in brain |
| Length | 83 residues | 67 residues |
| Change from native IGF-1 (70 residues) | 13-residue N-terminal extension, plus arginine in place of glutamic acid at position 3 | First three residues (Gly-Pro-Glu) removed |
| How it avoids binding proteins | Substitution and extension | Deletion |
| Receptor | IGF-1 receptor | IGF-1 receptor |
| Main research areas | IGFBP versus receptor binding, serum-free cell culture, animal models of IGF action | IGFBP biology, local processing of IGF-1 in tissues, comparison with intact IGF-1 |
| Regulatory status | Not FDA approved; WADA S2 | Not FDA approved; WADA S2 |
| Full overview | IGF-1 LR3 research | IGF-1 DES research |
One problem, two answers
The N-terminal region of IGF-1, and the glutamic acid at position 3 in particular, is one of the surfaces that binding proteins use to grip the hormone. Researchers learned this partly from IGF-1 DES: when the naturally shortened form was purified and found to bind IGFBPs weakly, it pointed to that region (Ballard et al., 1996).
IGF-1 LR3 applies the same insight by engineering instead of deletion. Replacing Glu3 with arginine weakens binding-protein recognition, and a 13-residue leader fused to the N-terminus lowers it further. Francis and colleagues compared a series of these analogs and found that reduced binding-protein affinity, rather than changes at the receptor, explained their higher potency in cell assays (Francis et al., 1992).
IGF-1 LR3: the engineered analog
At 83 residues, IGF-1 LR3 is the larger of the two. Its receptor binding is broadly comparable to native IGF-1’s; what sets it apart is that it stays largely free in settings full of binding proteins, such as serum or cell cultures that secrete their own IGFBPs. That property made it a standard defined supplement in serum-free cell culture. In guinea pigs, infusion was associated with increased organ weight while the animals’ own IGF-1, IGF-II and binding-protein levels fell (Conlon et al., 1995).
Read the full IGF-1 LR3 research overview or view IGF-1 LR3.
IGF-1 DES: the natural truncated form
IGF-1 DES is the mature 70-residue hormone minus Gly-Pro-Glu, keeping the same three disulfide bonds. Because it occurs in tissue, it raises a biological question that LR3 does not: whether trimming the N-terminus is one way tissues adjust IGF-1 availability locally. The released tripeptide, Gly-Pro-Glu (GPE), is studied separately as a neuroactive peptide, so one cleavage could yield two signaling molecules (Ballard et al., 1996).
Read the full IGF-1 DES research overview or view IGF-1 DES.
Where their research overlaps
- Plasma binding across species: Lord and colleagues measured both variants against plasma binding proteins from rat, sheep, pig, human and chicken. Both associated far less than IGF-1, and the size of the difference depended on species (Lord et al., 1994).
- Insulin-like actions in animals: In fasting lambs, IGF-1 variants with weak IGFBP binding lowered blood glucose more strongly and for longer than IGF-1 (Tomas et al., 1997). In diabetic rats, the variants restored growth without reproducing every characteristic insulin effect (Tomas et al., 1993).
- Anti-doping detection: Both are prohibited in sport, and one mass spectrometry method detects LongR3-IGF-I, R3-IGF-I and des(1-3)-IGF-I together (Mongongu et al., 2021).
How researchers choose between them
- Studying a naturally occurring form or local IGF-1 processing: IGF-1 DES is the relevant tool, because it exists in tissue.
- Needing a defined, binding-protein-resistant ligand for cell culture: IGF-1 LR3 is the established choice.
- Isolating binding-protein effects: running native IGF-1, IGF-1 DES and IGF-1 LR3 under identical conditions shows how much of a response depends on IGFBPs.
What the research does not show
The core literature for both dates mainly from the late 1980s and 1990s and is in vitro or in animals. There are no controlled clinical studies of either. Results depend heavily on the binding-protein environment of the model, and species differences mean animal findings cannot be assumed to apply elsewhere. The pronounced glucose-lowering action of both in animal models is a known pharmacological property, not a sign of safety. Neither is an approved drug, and none of these findings describes the research material sold here.
Verify what you’re working with
These are full-length proteins with three disulfide bonds each, and the two differ in length by 16 residues, so identity and purity testing matter. Every Rogue batch is tested by an independent, ISO 17025 accredited U.S. lab, and the QR code on each vial opens that batch’s report on the lab’s own website. See how to read a peptide COA or browse the COA Library.
View IGF-1 LR3 on Rogue Compounds
References
- Francis GL, 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 1378742
- Ballard FJ, et al. Des(1-3)IGF-I: a truncated form of insulin-like growth factor-I. Int J Biochem Cell Biol. 1996;28(10):1085-1087. PMID 8930132
- Lord AP, et al. Differences in the association of insulin-like growth factor-I (IGF-I) and IGF-I variants with rat, sheep, pig, human and chicken plasma-binding proteins. J Endocrinol. 1994;140(3):475-482. PMID 7514204
- Tomas FM, et al. Insulin-like growth factor-I and more potent variants restore growth of diabetic rats without inducing all characteristic insulin effects. Biochem J. 1993;291(Pt 3):781-786. PMID 7683875
- Conlon MA, 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. J Endocrinol. 1995;146(2):247-253. PMID 7561636
- Tomas FM, et al. IGF-I variants which bind poorly to IGF-binding proteins show more potent and prolonged hypoglycaemic action than IGF-I in fasting lambs. J Endocrinol. 1997;155(2):377-386. PMID 9415072
- Mongongu C, 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 Test Anal. 2021;13(7):1256-1269. PMID 33587816
Research use only. Rogue Compounds products are sold strictly for laboratory research. They are not for human or veterinary use, and nothing in this article is medical advice. The studies cited here describe published research, not this product or any use of it.