IGF-1 DES, written in the literature as des(1-3)IGF-1, is a shortened form of insulin-like growth factor-1 that occurs in nature. It is the mature 70-residue hormone minus its first three amino acids, the tripeptide Gly-Pro-Glu, leaving a 67-residue chain with the same three disulfide bonds. It was first isolated from bovine colostrum and has also been identified in brain tissue.
Unlike engineered analogs, this variant was found rather than designed, and its discovery changed how researchers think about IGF-binding proteins (IGFBPs). This article looks at where the truncated form comes from, why losing three residues alters binding-protein recognition so sharply, what animal and binding studies have reported, and the open questions that remain.
At a glance
- Class: Naturally occurring truncated IGF-1 variant; IGF-1 receptor agonist with low IGFBP affinity
- Origin: Isolated from bovine colostrum and also found in brain; reviewed by Ballard and colleagues (Ballard et al., 1996)
- Structure: 67 residues (IGF-1 lacking N-terminal Gly-Pro-Glu), three disulfide bonds; formula, molecular weight and CAS for each batch are given on the Certificate of Analysis
- Main research areas: IGFBP biology, local processing of IGF-1 in tissues, comparison with intact IGF-1 and engineered analogs, anti-doping detection
- Regulatory status: Not FDA approved for any use; WADA S2 (IGF-1 and its analogues)
Structure and origin
The truncated form came to light when IGF-1 was purified from natural sources. Material from bovine colostrum, and separately from brain, included a version of the hormone that was three residues shorter at the N-terminus but otherwise identical. Ballard and colleagues, whose group carried out much of the early work, summarized its discovery and properties in a short 1996 review (Ballard et al., 1996).
The missing segment is small, but its position matters. The N-terminal region of IGF-1, and Glu3 in particular, is one of the surfaces that IGFBPs use to grip the hormone. Removing Gly-Pro-Glu takes that contact away, so the shortened protein is bound much more weakly by most binding proteins. The receptor-binding surfaces lie elsewhere in the molecule, which is why receptor activity is largely kept.
Two other details make the variant biologically interesting:
- It points to local processing. Its presence in tissue suggests that proteolytic trimming of the N-terminus could be one way tissues adjust IGF-1 availability locally, although how much this happens physiologically is still debated.
- The released tripeptide is active in its own right. Gly-Pro-Glu (GPE) is studied separately as a neuroactive peptide, so cleavage potentially yields two signaling molecules from one precursor.
The variant also shaped later drug design. The observation that losing Glu3 weakens binding-protein recognition informed engineered analogs such as R3-IGF-1 and Long R3 IGF-1, which reach a similar result by substitution rather than deletion.
Mechanism: what the research shows
Des(1-3)IGF-1 signals through the IGF-1 receptor, a receptor tyrosine kinase that activates PI3K/Akt and MAPK/ERK pathways once ligand binds. In a clean system without binding proteins, it behaves much like intact IGF-1. The difference appears when IGFBPs are present, whether added, secreted by cultured cells, or circulating in plasma. Intact IGF-1 is then largely sequestered, while the truncated form remains free to reach the receptor, so it acts as a more potent agonist in those conditions.
Plasma-binding studies quantified this across species. Lord and colleagues measured how IGF-1 and its variants associate with plasma binding proteins from rat, sheep, pig, human and chicken; the variants associated much less than IGF-1, and the extent of the difference varied by species (Lord et al., 1994).
Key areas of study
IGFBP biology
Comparing des(1-3)IGF-1 with intact IGF-1 under identical conditions is a standard way to isolate binding-protein effects. Any extra activity of the truncated form in a given system points to IGFBPs limiting native IGF-1 there (Ballard et al., 1996).
Cross-species plasma binding
The species comparison by Lord and colleagues remains a reference for choosing models, since the same variant can look very different depending on the binding-protein profile of the plasma it meets (Lord et al., 1994).
Insulin-like actions in animal models
In a fasting animal model, IGF-1 variants with weak IGFBP binding, including the truncated form, lowered blood glucose more strongly and for longer than IGF-1 (Tomas et al., 1997). In diabetic rats, IGF-1 and more potent variants were compared for growth-related measures and insulin-like metabolic effects; the variants did not reproduce every characteristic insulin effect (Tomas et al., 1993). Together these studies are used to examine how far free IGF-1 overlaps with insulin action.
Anti-doping detection
Because the truncated form differs from endogenous IGF-1 by only three residues, detecting it requires precise methods. Mongongu and colleagues described immunopurification followed by high-resolution mass spectrometry for des(1-3)-IGF-I alongside LongR3-IGF-I and R3-IGF-I (Mongongu et al., 2021).
What the evidence does not show
- Most published work dates from the late 1980s and 1990s and is in vitro or in animals. There are no controlled clinical studies of des(1-3)IGF-1.
- Its natural presence in colostrum and brain is established, but how much N-terminal trimming contributes to normal IGF-1 regulation in tissues has not been settled.
- Potency comparisons depend on the binding-protein environment, and species differences in plasma binding (Lord et al., 1994) limit how far animal results can be generalized.
- Its marked glucose-lowering action in animal models (Tomas et al., 1997) is a known pharmacological property, not a sign of safety.
- Findings on the GPE tripeptide concern that separate molecule, not the 67-residue protein.
- IGF-1 DES is not an approved drug and no regulator has evaluated it for any use.
Regulatory status
IGF-1 DES is not approved by the FDA for any use. IGF-1 and its analogues are covered by the World Anti-Doping Agency’s Prohibited List under S2 (peptide hormones, growth factors, related substances and mimetics). Rogue Compounds sells it as a research reagent only.
Handling and storage in the lab
Keep the lyophilized protein sealed and refrigerated at 2–8°C (36–46°F), protected from light.
Sourcing and documentation
IGF-1 DES is made in small batches for Rogue Compounds. Every vial carries a batch number and a QR code that opens the independent U.S. testing lab’s own report for that batch, and the same COA is posted on the product page and in the COA Library.
View IGF-1 DES on Rogue Compounds
References
- 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
- 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.