IGF-1 DES(1-3) Research, Specifications & Scientific Information

Introduction

IGF-1 DES(1-3) is defined by an absence. It is human insulin-like growth factor 1 with its first three residues — glycine, proline and glutamate — missing, and that deletion of three amino acids out of seventy changes its behaviour in cell culture by roughly an order of magnitude ^[3].

What makes the compound scientifically interesting is that it was found before it was made. In 1986 a variant insulin-like growth factor was isolated from adult human brain ^[2]; two years later the same truncated form was purified to homogeneity from bovine colostrum and fully sequenced ^[3]. It has since been reported from porcine uterus as well, and is thought to arise by post-translational cleavage rather than from a separate gene ^[11]. So this is a naturally occurring variant that a laboratory can also synthesise, which is an unusual position for a compound in this library to occupy.

It has no clinical literature. None. This page does not borrow one from recombinant human insulin-like growth factor 1, which is a different substance.

What Is IGF-1 DES(1-3)?

IGF-1 DES(1-3) is a 67-residue protein: the mature human insulin-like growth factor 1 chain beginning at what would be its fourth residue. The FDA/NCATS Global Substance Registration System names it both des(1-3) human insulin-like growth factor I and 4-70-insulin-like growth factor I (human), and records the sequence TLCGAELVDALQFVCGDRGFYFNKPTGYGSSSRRAPQTGIVDECCFRSCDLRRLEMYCAPLKPAKSA.

The parent molecule begins GPET…. Cutting GPE leaves a chain that starts at the threonine, and the three disulphide bonds that hold the insulin-like growth factor fold together are untouched by the cut — which is why the variant remains a functional receptor agonist rather than an inert fragment.

Two things follow from that, and they are the whole compound:

It still binds its receptor. Competition against radiolabelled insulin-like growth factor 1 at the type 1 IGF receptor on L6 myoblasts gave half-competition at 14 ng/mL for the variant against 20 ng/mL for the intact protein — comparable, and if anything slightly better ^[4].

It barely binds the binding proteins. Against the binding protein secreted by those same myoblasts, and against binding protein purified from MDBK-cell-conditioned medium, intact insulin-like growth factor 1 competed at least 60-fold better than the truncated variant ^[4].

It is not an approved medicine anywhere and has never been the subject of a clinical trial. A 1996 review by the group that characterised it observed that clinical opportunities had not yet been evaluated ^[11]; three decades later, that is still the position.

IGF-1 DES(1-3) Specifications

The 67-residue chain above is the sequence recorded in the FDA/NCATS Global Substance Registration System under UNII AG0WVP88OA, where the substance is also named 4-70-insulin-like growth factor I (human). It is the 70-residue human insulin-like growth factor 1 sequence with its first three residues — glycine, proline and glutamate — removed, which is what the name des(1-3) states. The register carries CAS registry number 112603-35-7 and a calculated average mass of 7370.0 g/mol, and publishes no molecular formula, so that field is shown as unknown rather than estimated. The register lists no structural modifications; the three disulphide bonds that hold the insulin-like growth factor fold together are implicit in the sequence rather than written into a single-letter string, so the linear notation is not a claim that the protein is linear. The variant is not purely synthetic in origin: it has been isolated from bovine colostrum, from adult human brain and from porcine uterus, and is thought to arise by post-translational cleavage of insulin-like growth factor 1.

Values that a public register does not carry are shown as not publicly characterised rather than estimated. Identifiers are reference values; the certificate of analysis supplied with a laboratory order is the record for a given lot.

How Does IGF-1 DES(1-3) Work?

The receptor is the type 1 insulin-like growth factor receptor, a receptor tyrosine kinase closely related to the insulin receptor — closely enough that its 1986 primary-structure determination was framed as a comparison between the two ^[1]. Nothing about the truncation changes which receptor the molecule engages.

What the truncation changes is availability. Circulating insulin-like growth factors are largely bound to a family of binding proteins that control how much reaches a receptor. A variant that binds those proteins weakly is not sequestered in the same way, so more of it is free.

That gives a testable prediction with a sharp edge: the variant's apparent potency should depend on how much binding protein the measuring system contains, and should collapse toward parity in a system with none. The prediction has been tested in both directions and it holds ^[7].

The mechanism is therefore not "a stronger growth factor". It is the same growth factor with one of its regulatory brakes removed.

IGF-1 DES(1-3) Mechanism of Action

In vitro research

The experiment that located the effect is a truncation series. Analogues of insulin-like growth factor 1 shortened by one, two, three, four and five residues from the N-terminus were synthesised and tested for stimulation of protein synthesis in rat L6 myoblasts. The concentrations producing a half-maximal response were 13 ng/mL for the intact protein, 10 ng/mL for des(1), 13 ng/mL for des(1-2), 1.5 ng/mL for des(1-3), 5.1 ng/mL for des(1-4) and 1200 ng/mL for des(1-5) ^[4].

Read that series as a whole rather than as a single number. Removing one residue does nothing. Removing two does nothing. Removing the third — the glutamate — produces an eight- to ninefold change. Removing a fourth partly reverses it, and removing a fifth destroys activity altogether by wrecking receptor binding. The effect is not a general consequence of shortening the chain; it is specific to position 3, which is exactly the position that the separately engineered LR3 analogue substitutes rather than deletes.

Comparative bioassay in the same cell line put the ordering plainly. Protein synthesis was stimulated and protein degradation inhibited in a coordinated response by all three colostrum-derived growth factors, with relative potency running truncated IGF-1 above IGF-1 above IGF-2, and the same ordering for DNA synthesis. The authors described the roughly tenfold effect of removing three residues as unexpected given what was then understood about the structure ^[3].

The negative control came later, from the fusion-analogue work: in chicken embryo fibroblasts, which secrete no detectable binding proteins into the medium, the binding-protein-evading analogues lost their advantage ^[7]. In binding-protein-rich systems the truncated variant and the LR3 analogue sat together at the top of the potency ordering, above the less modified constructs, above native insulin-like growth factor 1 — the order of decreasing binding-protein affinity, and nothing else.

What Is IGF-1 DES(1-3) Being Researched For?

Like the other binding-protein-evading analogues, it is mostly used to research something else. The published work falls into four lines:

• The function of the insulin-like growth factor binding proteins — the purpose the variant has served since it was characterised ^{[4, 7]}.
• Comparative anabolic pharmacology in rodents — where it is the high-availability comparator against native insulin-like growth factor 1 ^{[5, 6, 10]}.
• Clearance and distribution, including in disease states that disturb binding-protein concentrations ^[9].
• Glucose pharmacology in larger animals, in pigs and marmoset monkeys ^[12].

There is no human research on this variant. The clinical record that exists for recombinant human insulin-like growth factor 1 concerns the full 70-residue sequence, a different molecule, and nothing in that record transfers here. That distinction is the single most important thing on this page.

Preclinical Research on IGF-1 DES(1-3)

Animal research

The rodent work is the largest body of animal evidence and it is consistent with the in vitro account.

In dexamethasone-treated rats — a glucocorticoid-induced catabolic model — insulin-like growth factor 1 and its N-terminally modified analogues were compared by continuous subcutaneous infusion. The truncated variant and the LR3 analogue, the two that bind the binding proteins poorly, were approximately 2.5-fold more potent than the native protein on body-weight and nitrogen-retention measures. The authors attributed the difference to binding-protein handling rather than to receptor engagement, noting that dexamethasone combined with insulin-like growth factor 1 substantially raised plasma insulin-like growth factor binding protein 3 ^[5].

A companion study in the same model examined gut tissue specifically and reported that the N-terminally modified analogues induced marked growth of gut tissues ^[6]. Gastrointestinal tissue has been a recurring model for this class of compound, and it is the context in which the 1996 review suggested clinical evaluation might one day be warranted ^[11].

A reasonable objection to all of the above was that the advantage might be an artefact of continuous infusion, since a molecule that escapes sequestration could behave quite differently under a bolus. That was tested directly: the superior potency of the poorly binding analogues under infusion was maintained when they were administered by injection ^[10].

In larger animals, the variant was compared with insulin-like growth factor 1 and three other variants for acute effects on plasma glucose in pigs and in marmosets. Plasma glucose fell in proportion to the amount administered, the variants were consistently two- to threefold more potent than the native protein, and the ordering of potency tracked the ordering of binding-protein affinity, with the truncated variant at the extreme. The variants also suppressed glucose over a much longer period despite being cleared from the circulation faster ^[12].

Findings described in this section were observed in animals, and nothing in them establishes anything about humans.

Other Areas of IGF-1 DES(1-3) Research

Animal research

Two further lines are worth recording, one because it is methodological and one because it is negative.

Clearance in disease states was examined in rats with chronic renal failure, a condition in which binding-protein concentrations are disturbed. Plasma clearance of insulin-like growth factor 1, of the truncated variant and of the LR3 analogue were compared directly in that setting ^[9]. Clearance matters here more than it usually would, because the entire premise of this class of molecule is a change in distribution rather than in receptor activity.

The negative result came from the central nervous system. In adult rats subjected to unilateral hypoxic-ischaemic brain injury, agents were administered into the lateral cerebral ventricle two hours after the insult and neuronal loss assessed five days later across cortex, striatum, hippocampus, dentate gyrus and thalamus. Insulin-like growth factor 1 at 20 µg reduced neuronal loss in every region. The truncated variant did not — not at 2 µg, not at 20 µg, and only as a non-significant trend at 150 µg. Insulin-like growth factor 2 given alongside insulin-like growth factor 1 blocked the protective effect and reduced accumulation of labelled insulin-like growth factor 1 in the injured hemisphere ^[8].

The authors' interpretation is the reason this result belongs on the page: the binding proteins appear to target insulin-like growth factor 1 to the site of injury, so a variant that escapes them escapes the targeting too. Weak binding-protein affinity is an advantage in the bloodstream and a liability in the brain. Any general statement that this variant is "more potent" is contradicted by this experiment.

Findings described in this section were observed in animals.

Current Research Status

Status as of September 22, 2026. This block is rendered from maintained fields, not from prose, so it cannot go stale in one place and stay current in another.

IGF-1 DES(1-3) vs Related Compounds

The comparisons below are structural and evidential. No comparison of effect is made on this page.

Native IGF-1

The 70-residue human sequence beginning GPET. This variant is the same chain beginning at the threonine. Recombinant human insulin-like growth factor 1 is a separate substance with its own register record, its own clinical literature and its own regulatory position in the United States; none of that record concerns this variant.

IGF-1 LR3 :: The other classical binding-protein-evading analogue. It substitutes arginine for the glutamate at position 3 and adds a 13-residue N-terminal extension; this variant deletes the position-3 glutamate along with the two residues before it. The two reach the same place by opposite edits and behave similarly wherever both have been tested ^{[7, 5, 9]}. MGF and PEG-MGF :: Derived from an alternatively spliced transcript of the same gene, not from cleavage of the mature protein. Structurally unrelated to this construction despite sharing a family name.

Evidence base

Tesamorelin has an approved product and phase 3 trials. This variant has no clinical record of any kind. On a page that tiers its evidence, that is the difference that matters most.

Chemical & Molecular Characteristics

The sequence is a register record. TLCGAELVDALQFVCGDRGFYFNKPTGYGSSSRRAPQTGIVDECCFRSCDLRRLEMYCAPLKPAKSA is the 67-residue chain recorded under UNII AG0WVP88OA. Aligned against the parent protein it is residues 4 through 70, which is why the register's alternative name for the substance is 4-70-insulin-like growth factor I (human).

The single-letter string omits the disulphides. Six cysteines in that chain form three disulphide bonds that give the insulin-like growth factor domain its fold. The register lists no structural modifications for this substance because the folding is implicit in the sequence, not written into it. A linear string is not a statement that the protein is linear — and in this case the fold is precisely what survives the truncation.

The registry number is the register's. CAS 112603-35-7, carried in the same record. Its check digit is arithmetically consistent.

Two fields are blank on purpose. No molecular formula is published for this substance by the register, and no PubChem compound identifier resolves for the name. Both are shown as unknown rather than estimated. The molecular weight of 7370.0 g/mol is the register's own calculated average mass for the 67-residue chain.

It is a natural product as well as a reagent. The variant has been purified from bovine colostrum, isolated from adult human brain and reported from porcine uterus, and is believed to result from post-translational cleavage of insulin-like growth factor 1 rather than from a distinct transcript ^{[2, 3, 11]}. That origin is unusual in this library and is worth stating alongside the identifiers.

Frequently Asked Questions

Scientific References

1. Ullrich A, Gray A, Tam AW, et al.. Insulin-like growth factor I receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificity The EMBO journal; 1986. PMID 2877871 doi:10.1002/j.1460-2075.1986.tb04528.x
2. Carlsson-Skwirut C, Jörnvall H, Holmgren A, et al.. Isolation and characterization of variant IGF-1 as well as IGF-2 from adult human brain FEBS letters; 1986. PMID 3709807 doi:10.1016/0014-5793(86)80568-3
3. Francis GL, Upton FM, Ballard FJ, et al.. Insulin-like growth factors 1 and 2 in bovine colostrum. Sequences and biological activities compared with those of a potent truncated form The Biochemical journal; 1988. PMID 3390164 doi:10.1042/bj2510095
4. Bagley CJ, May BL, Szabo L, et al.. A key functional role for the insulin-like growth factor 1 N-terminal pentapeptide The Biochemical journal; 1989. PMID 2730580 doi:10.1042/bj2590665
5. Tomas FM, Knowles SE, Owens PC, et al.. Insulin-like growth factor-I (IGF-I) and especially IGF-I variants are anabolic in dexamethasone-treated rats The Biochemical journal; 1992. PMID 1371669 doi:10.1042/bj2820091
6. Read LC, Tomas FM, Howarth GS, et al.. Insulin-like growth factor-I and its N-terminal modified analogues induce marked gut growth in dexamethasone-treated rats The Journal of endocrinology; 1992. PMID 1613443 doi:10.1677/joe.0.1330421
7. 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 Journal of molecular endocrinology; 1992. PMID 1378742 doi:10.1677/jme.0.0080213
8. Guan J, Williams CE, Skinner SJ, et al.. The effects of insulin-like growth factor (IGF)-1, IGF-2, and des-IGF-1 on neuronal loss after hypoxic-ischemic brain injury in adult rats: evidence for a role for IGF binding proteins Endocrinology; 1996. PMID 8603600 doi:10.1210/endo.137.3.8603600
9. Gillespie CM, Hazel SJ, Walton PE, et al.. Effects of chronic renal failure on plasma clearance of insulin-like growth factor I, des-(1-3)IGF-I, and LR3IGF-I The American journal of physiology; 1996. PMID 8897852 doi:10.1152/ajpendo.1996.271.4.E649
10. Tomas FM, Lemmey AB, Read LC, et al.. Superior potency of infused IGF-I analogues which bind poorly to IGF-binding proteins is maintained when administered by injection The Journal of endocrinology; 1996. PMID 8708565 doi:10.1677/joe.0.1500077
11. Ballard FJ, Wallace JC, Francis GL, et al.. Des(1-3)IGF-I: a truncated form of insulin-like growth factor-I The international journal of biochemistry & cell biology; 1996. PMID 8930132 doi:10.1016/1357-2725(96)00056-8
12. Tomas FM, Walton PE, Dunshea FR, et al.. IGF-I variants which bind poorly to IGF-binding proteins show more potent and prolonged hypoglycaemic action than native IGF-I in pigs and marmoset monkeys The Journal of endocrinology; 1997. PMID 9415072 doi:10.1677/joe.0.1550377

Every identifier above is resolved against PubMed, Crossref or ClinicalTrials.gov at build time, and the title returned by the register is compared with the title stored here. A page does not publish if a reference fails to resolve.

Research-Use Information

For in vitro research use only. This material is a laboratory reagent. It is not a drug, food, dietary supplement, or cosmetic and is not for human or veterinary use, including ingestion, injection, or any other administration. No information on this page describes or implies any effect in humans or animals. Sold only to researchers under our Terms of Sale.