Shortened IGF-1 growth factor that dodges the body's blockers (des(1-3)-IGF-1)
A trimmed version of the natural growth signal IGF-1 that slips past the proteins which normally hold it back, showing stronger cell-growth and nerve-protecting effects in animal studies; experimental, not an approved drug.
- Class
- Truncated IGF-1 variant / growth factor analogue
- Status
- Not approved for any therapeutic indication; research-chemical market only
- Best-supported effect
- Near-complete IGFBP resistance and approximately 10× IGF-1R potency vs native IGF-1 (preclinical biochemical characterization); neuroprotective and neurotrophic effects in rodent CNS and retinal models
- Main caveat
- No human clinical trials for any indication; the central localized muscle growth claim is mechanistically plausible but has no human or directly applicable animal hypertrophy evidence in source
A researcher, an agent, or an algorithm wrote down the sequence and picked a target to hit.
An AI model like OpenFold3 or AlphaFold built a 3D structure and scored how well it fits the binding site.
A second contributor repeated the computation on their own hardware and the scores matched.
A chemistry service or a researcher ordered the sequence, it was manufactured, and mass spectrometry confirmed the right molecule was produced.
A binding or activity measurement confirmed that it actually does what the computer predicted — or didn't.
Snapshot
Class: Truncated IGF-1 variant / growth factor analogue
Evidence tier: Animal-only evidence
Status: Not approved for any therapeutic indication; research-chemical market only
Best-supported effect: Near-complete IGFBP resistance and approximately 10-fold greater IGF-1R potency vs native IGF-1 (preclinical biochemical characterization); neuroprotective and neurotrophic activity in rodent CNS and retinal models
Main caveat: No human clinical trials have been conducted for any indication; the central "localized muscle growth" claim has no human imaging or controlled evidence, and no directly applicable animal hypertrophy study is present in the available literature
What this is
IGF-1 DES — formally des(1-3)-IGF-1 — is a naturally occurring truncated form of insulin-like growth factor 1, first identified in bovine colostrum and later detected in the human central nervous system and other tissues. It lacks the first three N-terminal amino acids (Gly-Pro-Glu) of native IGF-1, which constitute the principal domain for binding to IGF-binding proteins (IGFBPs). This structural difference confers near-complete IGFBP resistance and an approximately 10-fold increase in potency at the IGF-1 receptor (IGF-1R) relative to native IGF-1. The very short plasma half-life — estimated at tens of minutes — is an intrinsic consequence of the truncation, not an engineered property; loss of IGFBP stabilization shortens circulating lifetime markedly.
The peptide was characterized through academic research programs from the 1980s onward, notably by groups including Gluckman (New Zealand) and Ballard/CSIRO (Adelaide), and entered the research-reagent market as a cell-culture and in vivo research tool. Unlike IGF-1 LR3 — an engineered long-acting analogue — DES was never developed as a therapeutic agent. Human therapeutic development has not been pursued. It is distinct from mecasermin (Increlex), the FDA-approved IGF-1 product.
Evidence map
| Evidence layer | Grade | What it supports |
|---|---|---|
| Human | None | No human trial data is present |
| Animal | Moderate | Neuroprotection in rodent hypoxic-ischemic brain injury; retinal neuroprotection in diabetic rat models; trophic effects on fetal brain tissue grafts; comparative CNS cholinergic activity vs native IGF-1 |
| In vitro | Moderate | IGFBP-independent IGF-1R binding and activation; dual effects on insulin release from isolated rat islets; comparative receptor-binding characterization vs native IGF-1 and IGF-2 |
| Computational | None identified | No computational or structural prediction data attached |
| Mechanism | Strong | IGF-1R agonism via PI3K/Akt/mTOR and Ras/MAPK pathways is well-established; IGFBP-independence is biochemically characterized across multiple independent research groups |
The animal evidence base is concentrated in neurological and retinal models from the 1980s–1990s. Skeletal muscle hypertrophy evidence — the primary rationale cited in the research-chemical and bodybuilding context — is not individually extracted from any published animal or human study. The community use rationale rests on the mechanistic IGFBP-independence and short half-life characterization rather than on controlled muscle-hypertrophy experiments.
Claim check
| Claim | Verdict | Evidence layer | Confidence |
|---|---|---|---|
| Near-complete IGFBP resistance and approximately 10× greater IGF-1R potency vs native IGF-1 | Supported (preclinical) | In vitro / animal | High |
| Neuroprotective and neurotrophic effects in rodent CNS and retinal models | Supported (animal) | Animal | Medium |
| Site-specific localized muscle hypertrophy at injection site in humans | Not established | Animal / in vitro | High — no human imaging, controlled human study, or directly applicable animal hypertrophy experiment supports this claim |
| Short half-life eliminates systemic risk | Weak (preclinical inference) | Animal / in vitro | Medium — shorter half-life reduces systemic exposure vs LR3; acute hypoglycemia and systemic IGF-1R activation are reduced, not absent |
Evidence-layer qualifier note: This is a preclinical-tier card. "Supported (preclinical)" and "Supported (animal)" are the correct verdict forms for positive findings. The localized hypertrophy claim that drives community use is the most prominent unvalidated claim on this card — mechanistically plausible, not directly studied.
Experimental exposure
This section reports exposure conditions used in animal experiments and preclinical studies. It does not establish human dosing.
| Context | System | Experimental condition | Duration / timepoint | Endpoint | Limitation |
|---|---|---|---|---|---|
| Animal experiment | Adult rats; hypoxic-ischemic brain injury model | Des(1-3)-IGF-1 vs native IGF-1 and IGF-2; exact dose not individually extracted in source | Post-injury | Neuronal survival; role of IGF-binding proteins | Rodent model; no human CNS translation established |
| Animal experiment | Diabetic rat retina model | Des(1-3)-IGF-1 treatment; exact dose not individually extracted in source | Predegenerative timepoints | IGF-1R and phospho-Akt (Thr308) immunoreactivity | Rodent diabetic model; no human ophthalmological translation established |
| Animal experiment | Fetal brain tissue grafts | Truncated IGF-1; exact dose not individually extracted in source | Acute / post-graft | Trophic activity in graft tissue | Brain graft preparation; not a standard in vivo model |
| In vitro / animal | Isolated adult rat islets of Langerhans | IGF-1 and DES comparative; exact concentrations not individually extracted | Perifusion timepoints | Insulin release (dual effect) | Isolated-islet preparation; does not characterize systemic pharmacokinetics |
| In vitro / binding assay | Recombinant IGF-1 / IGFBP preparation | Des(1-3)-IGF-1 vs IGF-1 and IGF-2; exact concentrations not individually extracted | Acute | IGFBP inhibition of biological activity | Biochemical assay; characterizes binding properties, not in vivo exposure |
Exact doses and concentrations used in the above experiments are not individually extracted from the available literature. Rows are presented to characterize experimental systems and endpoints studied, not as exposure references for other contexts.
Preclinical safety signals
| Signal | System | Notes |
|---|---|---|
| Acute hypoglycemia potential | Rodent islet studies; IGF-1 pharmacology extrapolation | Dual effect on insulin release documented in isolated rat islets; glucose lowering is shorter-duration than with LR3 but not absent, particularly at higher doses or with vascular administration |
| Mitogenic / proliferative risk with supraphysiologic IGF-1R stimulation | Theoretical; IGF-1 biology background | Supraphysiologic episodic IGF-1R activation in proliferating tissue is a recognized concern based on IGF-1 pharmacology; no chronic exposure or carcinogenicity study specific to DES is identified |
| Local injection-site tissue changes from repeated IM injection | Community observation; uncontrolled | Source describes community reports of local scarring, fibrotic palpable changes, and occasional sterile abscess with repeated injection into the same site; no controlled histological or imaging study is attached |
| Long-term safety in any species or system | Not established | No chronic animal toxicology, carcinogenicity, reproductive, or developmental safety data are individually extracted from the available literature |
Human safety data are absent from the available literature. All signals above are extrapolated from preclinical IGF-1 pharmacology or from uncontrolled community observations, not from systematic human safety surveillance.
Source also describes the following per available sources contraindications as precaution context: active or recent cancer (especially hormone-sensitive), diabetes or impaired glucose regulation, pregnancy and breastfeeding, pediatric use, active acromegaly or untreated pituitary tumor, and active injection-site infection. These are per available sources cautions based on mechanistic inference, not label exclusions from a controlled trial.
Regulatory status
| Region / body | Status | Notes |
|---|---|---|
| US (FDA) | Not approved | Per available sources, no FDA approval for any indication; distinct from mecasermin (Increlex); distributed via research-chemical channels labeled "not for human use"; Per available sources, distribution for human consumption as unauthorized under the FD&C Act; not a scheduled controlled substance per source |
| EU / UK / Canada | Not authorized | Per available sources, no authorization as a medicine in these jurisdictions; status is per available sources and has not been independently verified in this card-writing pass |
| Australia (TGA) | per available sources Schedule 4 | Per available sources, TGA treats DES as a Schedule 4 prescription-only substance; not independently verified |
| WADA | per available sources prohibited at all times | Per available sources, prohibition under WADA category S2 (peptide hormones, growth factors, related substances and mimetics) as an IGF-1 analogue; applies in and out of competition per source; current list status not independently refreshed in this card-writing pass |
All regulatory and anti-doping statuses above are source-bundle reported. Current status has not been independently verified against live regulatory or anti-doping lists in this authoring pass.
Mechanism
Des(1-3)-IGF-1 is an agonist at the IGF-1 receptor (IGF-1R), a receptor tyrosine kinase. The deletion of the N-terminal Gly-Pro-Glu tripeptide removes the primary IGFBP-binding domain, resulting in near-complete bioavailability at IGF-1R without sequestration by circulating binding proteins. Receptor activation initiates two well-characterized downstream cascades: the PI3K/Akt/mTOR pathway (associated with protein synthesis, glucose uptake, and cell survival) and the Ras/MAPK pathway (associated with proliferation and differentiation). Because circulating IGFBPs normally sequester native IGF-1, the IGFBP-independent DES variant reaches the receptor at proportionally higher free concentrations per molar dose — approximately 10-fold greater potency in characterized assay systems.
The intrinsically short plasma half-life (tens of minutes) reflects the loss of binding-protein stabilization, which normally prolongs native IGF-1 circulating half-life. Rapid clearance is the mechanistic basis for the community claim that effects are primarily local following intramuscular administration. However, the available literature notes that "local-only" is an approximation of the dominant effect, not a guarantee of zero systemic IGF-1R activation.
The N-terminal tripeptide Gly-Pro-Glu released by the truncation is itself described as neuroactive in available literature and has been characterized as a separate bioactive fragment. Its pharmacology is distinct from des(1-3)-IGF-1 acting as an IGF-1R agonist.
Chemistry
| Field | Value |
|---|---|
| Common name | IGF-1 DES; Des(1-3)-IGF-1; Truncated IGF-1; DES |
| Structure | N-terminally truncated form of human IGF-1; lacks first three residues (Gly-Pro-Glu) |
| Length | 67 amino acids (native IGF-1 is 70 aa; DES is the 4–70 fragment) |
| Topology | Linear |
| Key structural feature | Loss of N-terminal IGFBP-binding domain confers IGFBP independence |
| Disulfide bonds | Three disulfide bonds (inherited from native IGF-1 fold) |
| Full amino-acid sequence | Not individually extracted from available literature |
| Molecular weight | Not individually extracted from available literature |
| Molecular formula | Not individually extracted from available literature |
| CAS number | Not individually extracted from available literature |
| Sequence confidence | Needs review — sequence not extracted; structural description derived from source narrative |
The available literature characterizes DES as the naturally occurring 4–70 fragment of native IGF-1, lacking Gly-Pro-Glu at positions 1–3. Synthesis for research and market use has been as a recombinant or synthetic 67-residue fragment. Published research also notes documented supply-chain integrity issues: DES, IGF-1 LR3, and native IGF-1 are reportedly mislabeled for each other in the research-chemical market; no pharmaceutical-grade identity assurance pathway exists for commercial research-chemical products.
Open questions
- Human translation of localized hypertrophy: The central claim driving community use — site-specific muscle growth at the IM injection site — has no human imaging study, no controlled hypertrophy trial, and no human pharmacokinetic characterization of local versus systemic IGF-1R activation from a representative dose. This is the highest-priority evidence gap for the community use context.
- Controlled animal hypertrophy evidence: No directly applicable animal skeletal muscle hypertrophy experiment is individually extracted. The mechanistic rationale is based on IGFBP-independence and short half-life, not on a measured differential hypertrophy endpoint.
- Human dose-response for any endpoint: The community dose range described in available literature (20–75 mcg IM per site) is derived from rodent-model extrapolation. No human dose-ranging study for any endpoint — hypertrophy, glucose lowering, or adverse effects — has been conducted.
- Chronic local tissue histopathology: Repeated IM injection of a mitogenic peptide into the same anatomical site raises plausible concerns around fibrosis, chronic inflammation, and fibroblast dysregulation. No systematic imaging or histological study is identified.
- Cancer-risk quantification from episodic supraphysiologic IGF-1R activation: The epidemiological literature linking IGF-1 to cancer is based on chronic-exposure associations. The risk implications of repeated short pulses of supraphysiologic IGF-1R stimulation in muscle tissue are unquantified.
- Supply-chain identity and purity: available literature identifies documented mislabeling of DES, LR3, and native IGF-1 in research-chemical supply chains as an active integrity concern. No pharmaceutical-grade identity assurance exists for commercially available research-chemical DES products.
Research directions for this peptide, selected from the current sources — hypotheses you can explore and model. None of it is proven yet; tap any one to see the full thinking.
Does des(1-3)-IGF-1 outperform regular IGF-1 at protecting nerve cells specifically when brain inflammation is high?
If true, it could mean that patients with stroke, head injury, or ALS would benefit from this modified peptide where multiple IGF-1 trials have failed, because the standard molecule was being blocked before it could reach damaged neurons.
Could anchoring des(1-3)-IGF-1 to the collagen scaffolding of joints or bone make it stay active long enough to promote repair?
If true, it would convert a promising but practically useless molecule (it disappears too quickly to dose systemically) into a tool for treating osteoarthritis or accelerating bone healing after fracture, benefiting millions of people who currently have no good pharmacological options.
Could this modified IGF-1 regenerate the gut lining damaged by cancer chemotherapy more effectively than the standard molecule?
If true, it could reduce the severe mouth and gut sores that force many cancer patients to interrupt or stop treatment, potentially allowing more people to complete their chemotherapy courses.
Is des(1-3)-IGF-1 intrinsically better at grabbing its receptor, separate from the fact that it avoids binding proteins?
If true, it would mean the peptide is valuable even in tissues where blocking proteins are absent, expanding its potential uses and guiding the design of next-generation IGF-1 drugs with both properties deliberately engineered.
Does removing the three-amino-acid tip of IGF-1 change which version of its receptor it prefers, and could that make it more useful in metabolic disease?
If true, it would open a route to treating muscle wasting in type 2 diabetes and obesity using a naturally occurring molecule that acts more precisely in diseased tissue rather than all tissues equally, reducing unwanted side effects.
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.459502249956131 | openfold3-mlx |
| ranking score | 0.5779069066047668 | openfold3-mlx |
▸structural qualityopenfold3
| metric | value | note |
|---|---|---|
| gpde | 0.746 | global PDE — lower = better |
| disorder | 0.130 | fraction disordered |
| chain pair ipTM (A, B) | 0.460 | interface quality |
▸3-letter notation
▸recipeopenfold3-mlx 0.3.1
| parameter | value |
|---|---|
| model | openfold3-mlx 0.3.1 |
| weights | — |
| hardware | — |
| mlx version | — |
| python | — |
| random seed | — |
| msa strategy | — |
| diffusion samples | 1 |
| runtime | 137s |
| predicted by | mlx@peptide |
| predicted at | 2026-05-03 |
▸citationbibtex
@peptide{pep10912,
sequence = {GPETLCGAELVDALQFVCGDRGFYFNKPTGYGSSSRRAPQTGIVDECCFRSCDLRRLEMYCAPLKPAKSA},
target = {igf-1r},
author = {peptidemodel},
year = {2026},
status = {computed}
}