IGF-1 DES

01 · What it is

The evidence for DES(1-3)IGF-1 is real, internally consistent, and belongs almost entirely to one Australian laboratory studying catabolic rats between 1990 and 1997 — and the property that makes the molecule more potent than IGF-1 in a dish is the same property that makes it disappear fastest from the bloodstream.

DES(1-3)IGF-1 is human insulin-like growth factor 1 with the N-terminal tripeptide glycine-proline- glutamate removed, leaving 67 residues. The truncation reduces the molecule’s affinity for the insulin-like growth factor binding proteins by a large margin while leaving receptor binding intact, which raises its apparent potency in any system where binding proteins compete for ligand.

One fact separates it from every other compound in this family and deserves stating early, because it is routinely conflated with a claim it does not support: DES(1-3)IGF-1 is not an invention. It occurs naturally. It has been isolated from bovine colostrum, human brain and porcine uterus, and it is generated by post-translational cleavage rather than by design ¹³. It is produced in serum by an acid protease acting on free IGF-I, and in the experiment that showed this, only the 7.5 kDa free fraction was susceptible — the binding-protein-associated pool was not ¹¹. That the molecule exists in mammals is a statement about biochemistry. It is not evidence that administering it does anything useful in a person, and no study has tested that question.

The literature runs to 195 records, concentrated between 1991 and 1997, and divides in two. The larger half is anabolic work in catabolic rodent models, dominated by a single group — Ballard, Francis, Read, Tomas and Wallace, working between the CSIRO Division of Human Nutrition and the University of Adelaide, whose names appear on most of the primary papers cited below. The smaller half is reagent use: DES(1-3)IGF-1 as the ligand that shows an effect is binding-protein-independent ²², and as the radioligand that evades binding-protein interference in IGF-1 immunoassays ¹².

No human study is indexed. Not a pharmacokinetic study, not a tolerability study, not a trial. A 2026 review of unregulated compounds acting on the growth hormone–IGF-1 axis places analogues of this kind in its lowest evidence tier, defined by a complete absence of human studies ²⁴.

02 · Evidence at a glance

Evidence grade

Preclinical — no human study of any kind is indexed

Structure

67 residues; human IGF-1 lacking the N-terminal tripeptide Gly-Pro-Glu

Origin

Naturally occurring; isolated from bovine colostrum, human brain and porcine uterus ¹³

Endogenous generation

By an acid protease acting on free, unbound IGF-I in serum ¹¹

Design consequence

Greatly reduced binding-protein affinity; receptor binding retained

Indexed records

195, concentrated 1991–1997

Human trials

None

Human subjects to date

0

Principal research base

One Australian group across most primary papers ^1,3,4,7,8,13

Reproducible animal finding

Anabolic in catabolic rodent models — diabetic ⁴, dexamethasone-treated ⁸, renal failure ⁷, gut-resected ³

Potency versus IGF-1

At least equal in diabetic rats ⁴; 3–5 fold in olfactory bulb culture ¹⁰

Pharmacokinetic weakness

Binding-protein association essentially absent ²; rapid catabolism in vivo ²⁰

Approval status

None, any jurisdiction

03 · Mechanism of action

The receptor is unchanged

DES(1-3)IGF-1 binds the type 1 IGF receptor with affinity comparable to native IGF-1 and activates the same downstream machinery — receptor autophosphorylation, insulin receptor substrate recruitment, and divergence into the PI3K/Akt and Ras/MAPK arms. In human colon carcinoma cells, cell-surface type 1 receptors bound IGF-I and des-(1-3)-IGF-I identically, and the difference between the two molecules lay entirely in whether the cell’s own binding proteins could intercept them ⁹. Nothing about the receptor interaction is novel. The molecule is native IGF-1 with a handle removed.

The handle that was removed

The N-terminal tripeptide Gly-Pro-Glu is the principal contact region for the binding proteins. Deleting it drops affinity for the whole family, which is why the truncated variant is more potent wherever binding proteins are present and no more potent where they are not. That distinction is demonstrable: in colon carcinoma cells every binding-protein form the cells produced was unable to bind des-(1-3)-IGF-I ⁹; in glioma cell lines the analogues and native ligands produced different proliferative responses traceable to the same mechanism ¹⁶.

The effect is quantitative rather than absolute. Binding protein 3 still inhibited des(1-3)IGF-I- induced receptor phosphorylation in a dose-dependent manner over a concentration range similar to that for IGF-I, alongside IGF-II and Long(R3)IGF-I ²². The escape is partial, and the literature that treats DES as a fully binding-protein-blind ligand overstates the case.

Feedback and secretion

Like IGF-1, the truncated variant participates in the negative feedback that governs the somatotropic axis. In cultured rat anterior pituitary cells, IGF-I, IGF-II and des(1-3)IGF-I all altered growth hormone and binding protein secretion, with the truncated variant showing the lowest half-maximal concentration of the three ⁶. Administration to diabetic rats induced binding proteins while having only a slight effect on measured IGF-I concentrations ⁴ — a result whose interpretation is complicated by the fact that immunoassays for IGF-I behave differently in the presence of a variant they may or may not detect ¹².

Clearance, and why it is the weak point

The design succeeds and then fails at the same step. Because DES(1-3)IGF-1 does not enter the ternary complex, it is not protected by it. In rats, association with binding proteins was greater for IGF-II, present for IGF-I, and essentially absent for the truncated analogue, with correspondingly faster plasma clearance ². In tumour-bearing nude mice, iodinated des(1-3)IGF-I catabolised very fast, with rapid appearance of non-precipitable iodine ²⁰. Clearance, degradation and organ distribution were mapped for IGF-I, des-(1-3)IGF-I and LR3IGF-I together in a rat model of chronic renal failure ¹⁴.

A molecule engineered to avoid the system that extends its half-life has a short half-life. This is not a defect in the design; it is the design.

04 · Key research findings

Anabolic effects in catabolic rodent models. This is the compound’s core literature and it is consistent. In diabetic rats, treatment increased weight gain, nitrogen retention and muscle protein synthesis, and the paper concluded that des(1-3)IGF-I is at least as potent as full-length IGF-I ⁴. In dexamethasone-treated rats, subcutaneous osmotic-pump administration partially reversed the catabolic state, and the variants outperformed IGF-I — the paper’s title says “especially IGF-I variants” ⁸. In rats with renal failure, both molecules improved nitrogen balance and food utilisation, and muscle protein degradation was significantly attenuated with des(1-3)IGF-I treatment but not significantly affected in either IGF-I group ⁷. In rats after removal of 80% of the jejunum and ileum, both enhanced growth over seven days ³. In lit/lit mice, a single 30 µg injection of the truncated variant produced greater effects than the same dose of IGF-I ¹.

Five models, one group, one direction: in an animal that is losing tissue, the truncated variant preserves more of it than IGF-1 does. Whether that generalises past 1997, past rodents, or past protocols designed by the laboratory that made the molecule, has not been tested.

Effects on differentiated and transformed cells. In olfactory bulb organ culture, des(1-3)IGF-I was 3–5 fold more potent than IGF-I on amino acid uptake in a dose-dependent response ¹⁰. In human colon carcinoma cells it promoted differentiation rather than proliferation, in an experiment designed to mimic an IGF-II autocrine loop ⁹. In rat ovarian theca-interstitial cells, both des(1-3)IGF-I and long R3-IGF-I produced greater effects on DNA synthesis than IGF-I ¹⁸. In human glioma cell lines, the analogues showed different proliferative effects from the native factors ¹⁶. In fibroblast-embedded collagen gels, des(1-3)IGF-I produced 4.5% gel contraction at 10 ng/mL, P < 0.01, where IGF-I required 30–100 ng/mL for comparable effect ¹⁷.

Higher potency at lower concentration is reproducible in culture, and culture is where the binding proteins the molecule was built to evade are most easily controlled — which makes these the least surprising results in the file rather than the most impressive.

Endogenous generation and the biochemistry of the variant. The definitional review of the molecule reports isolation from bovine colostrum, human brain and porcine uterus, and attributes it to post-translational cleavage ¹³. Serum acid protease activity generates it from free IGF-I but not from the binding-protein-associated pool ¹¹. Recombinant expression in Chinese hamster ovary cells established that both IGF-I and the potent truncated variant could be secreted and purified from a mammalian system ⁵.

The natural occurrence is well established. The inference sometimes drawn from it — that an endogenous molecule is a safe one to inject — does not follow, and nothing in this literature tests it.

Effects on glucose handling. In transgenic mice overexpressing binding protein 1, the hypoglycaemic response to IGF-I was attenuated relative to wild-type, while the responses to insulin and to des(1-3)IGF-I were not ¹⁵ — a clean demonstration that binding protein 1 modulates IGF-I but not the truncated variant. Separately, injections of binding protein 1 induced insulin release in normal and streptozotocin-diabetic rats, with des-variants used to dissect the mechanism ¹⁹. In cats with diabetes mellitus, total IGF-I measured by radioimmunoassay using des(1-3)IGF-I as radioligand tracked changes in the 140 kDa ternary complex ²¹.

The hypoglycaemia signal is the most clinically legible fact in this file: the variant retains IGF-1’s glucose-lowering action and loses the buffering that normally restrains it.

Assay use. A substantial share of the modern citations are methodological. Immunoradiometric and radioimmunoassay measurements of IGF-I were compared using native and des(1-3)IGF-I as radioligands, the latter chosen because binding proteins interfere with the measurement ¹².

A compound whose largest modern footprint is as an assay reagent is a compound whose development programme stopped.

05 · Evidence overview

06 · Safety profile

Animal data. No formal toxicology exists. The rodent studies report physiological endpoints — weight gain, nitrogen balance, muscle protein synthesis, organ mass — over periods of three to seven days, at doses chosen to produce anabolic effects rather than to find a ceiling ^1,3,4,7,8. The mechanistically foreseeable risk is hypoglycaemia, and the transgenic mouse work confirms the relevant point: binding protein 1 attenuates the hypoglycaemic response to IGF-I and does not attenuate the response to the truncated variant ¹⁵. None of these studies was designed as a safety study and none reports adverse events systematically.

Human data. None exists. There is no reported human exposure to DES(1-3)IGF-1 in the peer-reviewed literature at any dose, by any route, for any duration.

What is genuinely unknown. Whether the anabolic effects observed in acutely catabolic rats over one week occur in any other context. The dose-response ceiling in any species — no study reports a maximum tolerated dose. Repeat-dose toxicology, genotoxicity, carcinogenicity and reproductive toxicology, none of which has been performed. Whether the rapid catabolism documented in mice ²⁰ produces fragments with activity of their own. Immunogenicity, unassessed, and relevant because a truncated protein presents a neo-N-terminus. Whether sustained exposure influences the growth of existing neoplastic tissue: the compound promoted differentiation in one carcinoma line ⁹ and increased DNA synthesis in another primary cell type ¹⁸, and no animal study has asked the question. And whether the natural occurrence of the molecule in colostrum and brain ¹³ has any bearing on the safety of injecting a recombinant preparation of it — a question the literature raises by implication and has never addressed.

07 · US regulatory status

Current as of 6 September 2026. DES(1-3)IGF-1 is not approved as a drug in the United States or any other jurisdiction and is not a controlled substance.

The parent molecule is approved. Recombinant human IGF-1 holds marketing authorisation for growth failure in children with severe primary IGF-1 deficiency; a companion product complexing recombinant IGF-1 with recombinant binding protein 3 was developed and subsequently ceased to be available in the United States and Europe for short-stature indications ²³. That second product is worth noting in a guide to a molecule designed to escape binding proteins, because it was designed to do the opposite — to add one, deliberately, in order to prolong half-life and reduce side effects ²³.

Under the World Anti-Doping Code, insulin-like growth factor 1 and its analogues fall within the prohibited peptide hormones and growth factors class. Competitors should consult the current Prohibited List directly rather than rely on secondary summaries, including this one.

08 · Limitations of the evidence

1. There is no human evidence of any kind. No indexed study reports administration of DES(1-3)IGF-1 to a person. Every claim in this guide describes rodents or cells.

1. Research concentration is extreme, and it is the central weakness of this file. The anabolic findings that constitute the compound’s reputation come overwhelmingly from one laboratory group working across a seven-year window ^1,3,4,7,8,13. Independent replication of the whole-animal anabolic result, by a group with no stake in the molecule, is not present in the indexed record.

1. The models are acute and artificial. Streptozotocin diabetes, dexamethasone catabolism, surgical removal of 80% of the small intestine, induced renal failure, and a growth-hormone-deficient mouse strain ^1,3,4,7,8. Each isolates a catabolic mechanism over days. None resembles a physiological state, and none was followed beyond a week.

1. Animal-to-human translation is obstructed by the very system the compound targets. Binding-protein affinities, protease activity and ternary-complex composition differ across species. A molecule defined by its interaction with that system is a molecule whose behaviour should be expected to differ across species, and no bridging work exists.

1. The pharmacokinetics argue against the use the compound is put to. Binding-protein association is essentially absent ² and catabolism is rapid ²⁰. Potency measured in a dish, where clearance does not apply, is not potency in an animal, and the literature reports the first far more often than the second.

1. No randomised controlled trial exists, in any species, for any endpoint. The rodent work is controlled but not randomised in the sense the term carries in clinical research, and no comparative effectiveness question has been asked since 1997.

1. Publication bias cannot be estimated and is likely material. A literature this concentrated, in this era, on a molecule its authors developed, is the classic setting for unpublished null results. Nothing here permits a correction for it.

1. Immunoassay interference contaminates the record. DES(1-3)IGF-1 is used as a radioligand precisely because it behaves differently in IGF-1 assays ¹², which means some reported IGF-I concentrations in studies administering the variant ⁴ carry a methodological caveat the original papers do not always foreground.

1. This guide asserts absence from the indexed record, not absence in fact. No human study appears in PubMed. Unindexed and unpublished work cannot be excluded and cannot be cited.

09 · References

1. Gillespie C, Read LC, Bagley CJ, Ballard FJ. Enhanced potency of truncated insulin-like growth factor-I (des(1-3)IGF-I) relative to IGF-I in lit/lit mice. J Endocrinol. 1990 Dec;127(3):401–405.

   PMID 2280209 ↗

2. Ballard FJ, Knowles SE, Walton PE, et al. Plasma clearance and tissue distribution of labelled insulin-like growth factor-I (IGF-I), IGF-II and des(1-3)IGF-I in rats. J Endocrinol. 1991 Feb;128(2):197–204.

   PMID 2005410 ↗

3. Lemmey AB, Martin AA, Read LC, Tomas FM, Owens PC, Ballard FJ. IGF-I and the truncated analogue des-(1-3)IGF-I enhance growth in rats after gut resection. Am J Physiol. 1991 Feb;260(2 Pt 1):E213–E219.

   PMID 1996625 ↗

4. Tomas FM, Knowles SE, Owens PC, et al. Increased weight gain, nitrogen retention and muscle protein synthesis following treatment of diabetic rats with insulin-like growth factor (IGF)-I and des(1-3)IGF-I. Biochem J. 1991 Jun 1;276(Pt 2):547–554.

   PMID 1710892 ↗

5. McKinnon P, Ross M, Wells JR, Ballard FJ, Francis GL. Expression, purification and characterization of secreted recombinant human insulin-like growth factor-I (IGF-I) and the potent variant des(1-3)IGF-I in Chinese hamster ovary cells. J Mol Endocrinol. 1991 Jun;6(3):231–239.

   PMID 1883485 ↗

6. Simes JM, Wallace JC, Walton PE. The effects of insulin-like growth factor-I (IGF-I), IGF-II and des(1-3)IGF-I, a potent IGF analogue, on growth hormone and IGF-binding protein secretion from cultured rat anterior pituitary cells. J Endocrinol. 1991 Jul;130(1):93–99.

   PMID 1715381 ↗

7. Martin AA, Tomas FM, Ballard FJ, Read LC. Insulin-like growth factor I and its variant, des(1-3)IGF-I, improve nitrogen balance and food utilization in rats with renal failure. Miner Electrolyte Metab. 1992;18(2–5):264–268.

   PMID 1465072 ↗

8. 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. Biochem J. 1992 Feb 15;282(Pt 1):91–97.

   PMID 1371669 ↗

9. Remacle-Bonnet M, Garrouste F, el Atiq F, Roccabianca M, Marvaldi J, Pommier G. des-(1-3)-IGF-I, an insulin-like growth factor analog used to mimic a potential IGF-II autocrine loop, promotes the differentiation of human colon-carcinoma cells. Int J Cancer. 1992 Dec 2;52(6):910–917.

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10. Russo VC, Werther GA. Des (1-3) IGF-I potently enhances differentiated cell growth in olfactory bulb organ culture. Growth Factors. 1994;11(4):301–311.

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11. Yamamoto H, Murphy LJ. Generation of des-(1-3) insulin-like growth factor-I in serum by an acid protease. Endocrinology. 1994 Dec;135(6):2432–2439.

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13. Ballard FJ, Wallace JC, Francis GL, Read LC, Tomas FM. Des(1-3)IGF-I: a truncated form of insulin-like growth factor-I. Int J Biochem Cell Biol. 1996 Oct;28(10):1085–1087.

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14. Gillespie CM, Hazel SJ, Walton PE, Martin AA. Effects of chronic renal failure on plasma clearance of insulin-like growth factor I, des-(1-3)IGF-I, and LR3IGF-I. Am J Physiol. 1996 Oct;271(4 Pt 1):E649–E657.

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