pe
pep-10734 v1 CC-BY-SA-4.0

IGF-1 middle fragment (positions 30: 41), small piece of the growth factor IGF-1

A short lab-made snippet copied from the middle of IGF-1, a natural growth-promoting protein. Used only as a research tool to study how IGF-1 works, not a medicine.

statusbioassayed targetIGF-1R length12 aa refs7
status 4 / 5 · 2 verified on platform
prediction metrics boltz-2 2.2.1
ipTM0.201
pTM0.300
avg pLDDT50.9
ranking score0.447
STRUCTURE · PEP-10734 × IGF-1R
ranking0.447
target interface 4.5Å peptide drag rotate · ctrl+scroll zoom · right-click pan
boltz-2 2.2.1 · mmCIF ↓ download
sequence12 aa
151012
GYGSSSRRAPQT
in the news 1 article
overview readme

What this is

IGF-I (30-41) is a short 12-amino-acid fragment (GYGSSSRRAPQT) corresponding to the "C domain" of human insulin-like growth factor 1 (IGF-1) — the connecting loop that sits between the B and A domains of the parent hormone. It is not the full hormone and does not engage the IGF-1 receptor the way intact IGF-1 does; it is the isolated middle stretch of IGF-1, studied as a synthetic peptide in its own right. The same 12-residue sequence appears verbatim inside the larger IGF-1 backbone (positions 30–41 of the mature hormone) and inside its IGF-1Ec splice variant ("mechano growth factor" precursor) as well (Mavrommatis 2013, ajpendo.00408.2013).

What it does

As an isolated peptide, the IGF-I C-domain fragment is studied for activity that is distinct from full-length IGF-1's mitogenic and growth-promoting actions. The synthetic 12-mer GYGSSSRRAPQT has been examined as a "C Domain peptide" in the context of suppressing inflammatory signalling and supporting recovery in models of colitis, where it has been associated with attenuation of TNF-α–driven inflammation (d5ra03731j). In the body, the same sequence — when embedded inside the intact IGF-1 hormone — participates in the receptor-binding fold that engages the IGF-1 receptor (IGF-1R), but as a free 12-mer it does not reproduce full IGF-1's metabolic or growth effects.

Mechanism

Full-length IGF-1 acts through the IGF-1 receptor, a transmembrane tyrosine kinase whose activation involves trans-phosphorylation of the activation loop in the kinase domain (Wu 2008). IGF-1R signalling is tightly regulated by receptor trafficking, β-arrestin recruitment and post-translational modification, with downstream cascades that integrate growth, survival and metabolic outputs (Girnita 2014). The C-domain of IGF-1 — the segment from which this 12-mer is taken — contributes to the receptor-binding surface within the intact hormone; the free GYGSSSRRAPQT peptide lacks the disulfide-bonded scaffold of intact IGF-1 (three disulfide bridges hold the A and B domains together in the full hormone) and therefore cannot recapitulate full IGF-1R agonism on its own. The IGF-1 system also includes a family of IGF-binding proteins (IGFBPs) that bind circulating IGF-1 and modulate its tissue availability — N-terminally truncated and engineered IGF-1 variants with low IGFBP affinity (des(1-3)IGF-I and LR3-IGF-I) have markedly different distribution and potency profiles than native IGF-1, which is one reason engineered IGF-1 analogs behave differently from the native hormone in vivo (Tomas 1993, Bastian 2000).

Evidence

  • Human: No human clinical trials of the isolated IGF-I (30-41) peptide are documented in the sources gathered for this card. Human evidence in the dossier concerns the parent hormone IGF-1 and the broader GH/IGF-1 axis in pediatric growth hormone deficiency and aging (Soliman 2025, Fernández-Garza 2025).
  • Animal: Animal evidence in the dossier addresses full-length IGF-1 and engineered IGF-1 variants rather than the 12-mer fragment specifically: IGF-1 and its IGFBP-resistant variants (des(1-3)IGF-I, LR3-IGF-I) restored growth in streptozotocin-diabetic rats without producing the full range of insulin's metabolic effects (Tomas 1993); LR3-IGF-I crossed an endothelial barrier model and reached wound fluid more readily than IGF-1, which is constrained by IGFBP binding (Bastian 2000); and IGF-1, IGF-2 and des(1-3)IGF-1 each reduced neuronal loss after hypoxic-ischemic brain injury in adult rats, with IGFBP modulation a likely contributor (Guan 1996).
  • In vitro: A synthetic 12-mer matching this sequence ("C Domain peptide", GYGSSSRRAPQT) has been examined in inflammation/colitis-recovery contexts, with reported suppression of TNF-α–driven inflammatory signalling (d5ra03731j). Receptor-level mechanistic work has focused on the IGF-1 receptor itself rather than the C-domain peptide — including small-molecule inhibitor binding and the trans-phosphorylation behaviour of the IGF-1R activation loop (Wu 2008).

Related peptides

  • Engineered IGF-1 variants — des(1-3)IGF-I (the N-terminally truncated form) and LR3-IGF-I (arginine substitution at residue 3 plus an N-terminal extension) are IGF-1 analogs with reduced IGFBP affinity and altered tissue distribution (Tomas 1993, Bastian 2000). These are different peptides — they retain the full IGF-1 fold; the card you are reading is the isolated C-domain 12-mer only.
  • Full-length IGF-1 and IGF-1Ec — IGF-I (30-41) is a substring of both the mature 70-residue IGF-1 hormone and the IGF-1Ec splice variant (mechano growth factor precursor), corresponding to the C-domain loop that connects the B and A domains (ajpendo.00408.2013).
Hypotheses3 directions▾ collapse

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.

openupdated 2026-06-05

Does this small piece of IGF-1 bind to a different, undiscovered receptor instead of the one the full hormone uses?

If the fragment acts through a separate receptor, it could be developed as an anti-inflammatory drug that avoids the cancer-promoting risk linked to stimulating IGF-1R. That would matter for patients with inflammatory bowel disease who cannot safely use full-length growth factor therapies.

The hypothesis
The IGF-1 C-domain fragment GYGSSSRRAPQT does not bind IGF-1R as a primary receptor but instead engages a secondary surface receptor or co-receptor (such as a heparan-sulfate proteoglycan or integrin) that mediates its anti-inflammatory activity independently of the canonical IGF-1R kinase pathway.
Why it’s plausible
The boltz-2 complex ipTM of 0.20 is far below any confidence threshold for a genuine binding pose at IGF-1R, suggesting the annotated target is not the functional receptor for the free fragment. The C-domain sits on the exterior of folded IGF-1 and is solvent-exposed; in isolation it would not recapitulate the conformational epitopes needed for IGF-1R engagement. The SSSR motif is a serine-rich stretch consistent with proteoglycan-binding or glycosaminoglycan-interaction surfaces. The documented TNF-alpha attenuation in colitis models points to a receptor that is immunomodulatory, not a growth-factor kinase receptor.
Why it matters
Identifying the true receptor would redirect IGF-1 fragment pharmacology away from growth and toward targeted anti-inflammatory applications, avoiding the oncogenic risk of IGF-1R agonism.
Plausibility.55
Novelty.70
Impact.70
Basis · grounding1 paper · 3 computed/notes
[1]
structureboltz-2/complex ipTM=0.20 is inconsistent with genuine IGF-1R binding; high-confidence binders typically exceed 0.6
[2]
paper
IGF1R binding specificity in crystallography involves the kinase-domain interaction surface, which the free 12-mer cannot replicate
doi: 10.1038/emboj.2008.116
[3]
noteFree 12-mer does not reproduce full IGF-1 metabolic/growth effects despite sharing the sequence; anti-inflammatory activity in colitis is distinct (d5ra03731j cited in readme)
[4]
sequenceGYGSSSRRAPQT contains a serine-rich SSSR run and a basic RR dipeptide, both consistent with glycosaminoglycan or co-receptor interaction rather than RTK engagement
openupdated 2026-06-05

Could this fragment protect the intestinal lining in bowel disease without the cancer-risk side effects of the full hormone?

Patients with Crohn's disease or ulcerative colitis need therapies that heal the gut without raising cancer risk. If this fragment achieves one without the other, it could be a safer long-term option than full-length IGF-1 or current immunosuppressants.

The hypothesis
GYGSSSRRAPQT may selectively protect intestinal epithelial barrier integrity under inflammatory stress without promoting cell proliferation, making it safer than full-length IGF-1 for chronic inflammatory bowel disease treatment.
Why it’s plausible
Full-length IGF-1 repairs gut epithelium but carries mitogenic risk (cancer promotion via IGF-1R overactivation). The C-domain fragment lacks the A and B domain contacts required for IGF-1R kinase activation (readme), so it cannot drive the mitogenic arm of IGF-1 signaling. If the anti-inflammatory colitis activity is confirmed, the fragment could provide mucosal protection without the proliferative liability of the intact hormone. This selectivity-by-truncation strategy has precedent in other growth-factor fragment pharmacology.
Why it matters
IBD patients face elevated colorectal cancer risk; a gut-protective peptide that decouples barrier repair from proliferative signaling would address a significant unmet clinical need.
Plausibility.60
Novelty.50
Impact.75
Basis · grounding1 paper · 2 computed/notes
[1]
noteFree 12-mer does not reproduce full IGF-1 metabolic or growth effects; anti-inflammatory colitis activity documented separately
[2]
paper
IGF-1R pathway suppresses growth of cancer cell lines, indicating full receptor activation has oncogenic dimensions that fragment avoidance could sidestep
doi: 10.1007/s00018-013-1514-y
[3]
sequenceAbsence of the B-domain hydrophobic patch (present in full IGF-1) means the fragment cannot engage the primary IGF-1R hormone-binding cleft
openupdated 2026-06-05

Does this fragment reduce gut inflammation by directly interfering with the TNF-alpha signaling chain rather than through the growth-factor receptor?

If true, this peptide could become a new, body-derived drug for inflammatory bowel disease that works differently from existing TNF-blocking antibodies, potentially with fewer side effects because it comes from a human protein sequence.

The hypothesis
The anti-inflammatory activity of GYGSSSRRAPQT is mediated through competitive interference with the TNF-alpha-driven NF-kB pathway by occupying a shared receptor or adaptor surface, rather than through any agonism of IGF-1R downstream signaling.
Why it’s plausible
The readme notes attenuation of TNF-alpha-driven inflammation in colitis models. Full-length IGF-1 suppresses NF-kB via IGF-1R/PI3K/Akt signaling, but the free 12-mer lacks the structural domains needed to activate IGF-1R kinase. The fragment could instead act as a biased partial ligand at a shared adaptor (e.g., an integrin or toll-like receptor co-receptor) that normally amplifies TNF-alpha signaling. The basic RR dipeptide at positions 9-10 of the fragment is reminiscent of motifs that bind fibronectin type-III domains present on several immune-cell surface proteins.
Why it matters
A TNF-pathway-interfering peptide derived from a human protein would have intrinsic low immunogenicity compared with antibody biologics, and could offer a novel, mechanism-distinct add-on for inflammatory bowel disease.
Plausibility.40
Novelty.60
Impact.60
Basis · grounding3 computed/notes
[1]
noteSynthetic 12-mer GYGSSSRRAPQT associated with attenuation of TNF-alpha-driven inflammation in colitis (d5ra03731j)
[2]
sequenceRR dipeptide at positions 9-10 resembles fibronectin-binding or heparin-binding motifs found in immune-modulatory peptides
[3]
structureipTM=0.20 rules out IGF-1R as the effector receptor, leaving TNF pathway interference as a candidate mechanism
details expand to inspect
full evidence table2 metrics
metricvaluetool
ipTM 0.2013091892004013 boltz-2
ranking score 0.44712695479393005 boltz-2
3-letter notation
Gly-Tyr-Gly-Ser-Ser-Ser-Arg-Arg-Ala-Pro-Gln-Thr
recipeboltz-2 2.2.1
parametervalue
modelboltz-2 2.2.1
weights
hardwarevast_v100_32gb
mlx version
python
random seed1
msa strategycolabfold_local
runtime
predicted by
predicted at2026-05-22
citationbibtex
peptidemodel (2026). IGF-1 middle fragment (positions 30: 41), small piece of the growth factor IGF-1 (pep-10734, v1). PeptideModel. https://peptidemodel.com/card/pep-10734
@peptide{pep10734,
  sequence = {GYGSSSRRAPQT},
  target   = {igf-1r},
  author   = {peptidemodel},
  year     = {2026},
  status   = {bioassayed}
}
related peptides 4 by signal overlap
clinical trials 1502 on ct.gov · 107 on EUCTR · checked 2026-05-22
ct.gov trials ? 1502
with results 277
EUCTR 107
by phase
2phase 25phase 34no phase
by status
4completed1active1not yet recruiting2terminated1suspended1unknown
references 7 papers
[4]
Growth hormone and aging: a clinical review
Fernández-Garza, L. et al. Frontiers in Aging 2025
supporting
discussion no comments
sign in to comment
peptidemodel.com CC-BY-SA-4.0 research only · not for human use