IGF-II growth factor fragment (IGF-II 33-40)
A tiny piece of IGF-II, a natural body growth factor; studied in the lab for how it interacts with growth signals, research tool only, not an approved drug.
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.
Named peptide fragment — synthesized for research; ClinicalTrials.gov trials registered for parent compound or class
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Endogenous peptide fragment — receptor binding/activity established in published literature; CT.gov evidence
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What this is
IGF-II (33-40) is an eight-amino-acid fragment of insulin-like growth factor II (IGF-II), a small protein hormone that the body makes naturally. The stored sequence here, SRVSRRSR, corresponds to a short stretch of residues from the middle of the parent IGF-II molecule rather than the full hormone. IGF-II itself is one of two insulin-like growth factors (the other being IGF-I) that signal mainly through the type 1 IGF receptor (IGF-1R) and play a central role in growth, tissue repair, and metabolism (LeRoith 2021).
This card describes a short peptide fragment derived from that larger hormone. It should not be conflated with intact IGF-II or with IGF-I — the biology summarised below comes from work on the full-length ligands and on the IGF-1R receptor, because that is what the dossier supports. Fragment-specific evidence is sparse.
What it does
In its full-length form, IGF-II binds to the same receptor used by IGF-I — the type 1 insulin-like growth factor receptor (IGF-1R), a transmembrane tyrosine kinase. Ligand binding relaxes conformational restraints in the receptor's dimeric ectodomain and triggers transphosphorylation of the intracellular kinase domains, launching downstream signalling that drives cell growth, differentiation, and survival (Xu 2018, Girnita 2014). IGF-1R is closely related to the insulin receptor and the two can heterodimerise, with their isoform composition shaping the metabolic versus mitogenic balance of the response (Belfiore 2017).
What the isolated SRVSRRSR fragment does on its own — whether it binds the receptor, modulates IGF binding-protein interactions, or has any independent activity — is not documented in the sources gathered for this card.
Mechanism
The IGF-1R is a disulfide-linked α₂β₂ homodimer in the receptor tyrosine kinase family. A single IGF molecule engages the receptor across both half-sites of the ectodomain; binding shifts the autoinhibited dimer into an active configuration that allows the two intracellular kinase domains to transphosphorylate each other on activation-loop tyrosines (Xu 2018). The activated receptor then recruits IRS adaptors and Shc, feeding into the PI3K–Akt and Ras–MAPK pathways that mediate the growth, anti-apoptotic, and proliferative effects of IGF signalling (Girnita 2014).
Circulating IGFs do not travel free in plasma — they are carried by a family of IGF binding proteins (IGFBPs) that regulate ligand availability at target tissues. Engineered IGF-I variants that bind IGFBPs poorly, such as des(1-3)IGF-I and Long-R3-IGF-I (LR3-IGF-I, with an N-terminal extension and an Arg substitution at position 3), are more potent in vivo than native IGF-I because more of the injected dose reaches the receptor (Tomas 1993). The same logic underlies the increased delivery of LR3-IGF-I from blood into extracellular wound-fluid sites compared with native IGF-I, where IGFBPs slow endothelial transit (Bastian 2000). These observations describe the parent ligands, not the SRVSRRSR fragment.
History
IGF-I and IGF-II were characterised in the 1970s as the "somatomedin" activities mediating many of growth hormone's effects on tissue growth. Decades of work since have mapped the IGF axis — ligands, six high-affinity IGFBPs, and the IGF-1R and IGF-2R receptors — into one of the better-studied endocrine systems, with clinical interest spanning growth disorders, diabetes, ageing, and oncology (LeRoith 2021, Fernández-Garza 2025). The dossier does not contain a primary record of when or by whom the IGF-II (33-40) fragment specifically was first synthesised or studied.
Evidence
- Human: No human trials of the SRVSRRSR fragment itself are present in the dossier. A first-in-human study of a PEGylated recombinant full-length human IGF-I has been reported (Kletzl 2017), and a clinical review summarises growth hormone and IGF-1 use in aging contexts (Fernández-Garza 2025) — both relate to parent IGF ligands rather than this fragment.
- Animal: Rat work on full-length IGF-I and on the LR3-IGF-I variant has shown dose-dependent growth and wound-fluid delivery effects (Tomas 1993, Bastian 2000). No animal data on IGF-II (33-40) is present in the dossier.
- In vitro: Structural and signalling work on IGF-1R itself (Xu 2018) and on receptor regulation (Girnita 2014, Belfiore 2017) provides the receptor-side picture. The dossier contains no in vitro characterisation of the isolated SRVSRRSR fragment.
Open questions
- Whether the isolated SRVSRRSR octapeptide binds IGF-1R, IGFBPs, or any other target with measurable affinity.
- Whether it has agonist, antagonist, or no activity at the IGF-1R, given that IGF-1R binding by the parent ligand depends on multiple contact regions distributed across the IGF molecule (Xu 2018).
- Pharmacokinetics, proteolytic stability, and tissue distribution of the fragment have not been reported in the sources reviewed.
- Whether the fragment can serve as a tool reagent (e.g. as a competitive probe for parent-ligand contacts) or has any therapeutic relevance is not addressed in the dossier.
Regulatory status
- US/EU: Not an approved drug. IGF-II (33-40) is a research peptide fragment; no regulatory authorisation is recorded.
- WADA: Full-length IGF-1 and related growth factors fall under WADA's prohibited list (S2, peptide hormones, growth factors and related substances). The status of short IGF-II fragments is not separately addressed in the dossier sources; treat parent-ligand restrictions as the relevant policy frame for context, not as a verdict on this specific fragment.
Related peptides
- IGF-I and its engineered variants des(1-3)IGF-I and LR3-IGF-I — used in the rat studies above to probe how IGFBP binding shapes in vivo potency and tissue delivery (Tomas 1993, Bastian 2000).
- PEGylated recombinant human IGF-I — tested in a first-in-human pharmacokinetic study (Kletzl 2017).
- Full-length IGF-II — the parent hormone from which this fragment is derived.
Internal cross-reference links to other Peptidopedia cards have been omitted because the relevant pep-ids could not be verified from the dossier.
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.
Is this peptide clinging to its target mainly because it is highly charged, rather than fitting precisely?
If true, chemists would know to redesign the peptide with a better balance of charges so it binds more specifically. This could lead to drugs that hit only the intended target and cause fewer side effects.
Could a very short piece of IGF-II stick to its receptor in an unexpected place?
If true, doctors might one day use ultra-small peptides to gently dial growth signals up or down, instead of flooding the body with large hormones. This could mean safer treatments for children with growth disorders or adults with certain cancers.
Could this short fragment stick to the insulin receptor just as strongly as to its intended target?
If true, drug developers would know early that this peptide is not selective enough on its own. They could then engineer in extra specificity before spending years on development, avoiding drugs that accidentally trigger blood sugar crashes or unwanted cell growth.
Could this peptide find tumors simply because it carries a strong positive charge?
If true, it could be attached to chemotherapy drugs like a guided missile, carrying toxic payloads straight to tumors while sparing healthy tissue. Cancer patients could receive stronger treatments with fewer side effects.
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.2799915671348572 | boltz-2 |
| ranking score | 0.5943511724472046 | boltz-2 |
▸structural qualityopenfold3
| metric | value | note |
|---|---|---|
| gpde | 1.983 | global PDE — lower = better |
| disorder | NaN | fraction disordered |
▸3-letter notation
▸recipeboltz-2 1.0
| parameter | value |
|---|---|
| model | boltz-2 1.0 |
| weights | — |
| hardware | nvidia_nim_api |
| mlx version | — |
| python | — |
| random seed | — |
| msa strategy | none |
| diffusion samples | 1 |
| runtime | — |
| predicted by | mlx@peptide |
| predicted at | 2026-04-24 |
▸citationbibtex
@peptide{pep10735,
sequence = {SRVSRRSR},
target = {igf-1r},
author = {peptidemodel},
year = {2026},
status = {bioassayed}
}