pe
pep-10786 v1 CC-BY-SA-4.0

IGF-1 growth-factor fragment (residues 24: 41)

A small piece of IGF-1, one of the body's natural growth signals; used in lab research to study how growth signals work. Experimental, not an approved drug.

statussynthesized targetIGF-1R length18 aa refs11
status 4 / 5
prediction metrics boltz-2 2.2.1
ipTM0.208
pTM0.286
avg pLDDT50.1
ranking score0.442
STRUCTURE · PEP-10786 × IGF-1R
ranking0.442
target interface 4.5Å peptide drag rotate · ctrl+scroll zoom · right-click pan
boltz-2 2.2.1 · mmCIF ↓ download
sequence18 aa
15101518
YFNKPTGYGSSSRRAPQT
in the news 1 article
overview readme

What this is

IGF-1 (24–41) is an 18-amino-acid fragment carved out of the middle of human insulin-like growth factor 1 (IGF-1). It corresponds to the tail end of the IGF-1 B-domain together with the full C-domain — the loop that sits between the two cysteine-rich halves of the parent hormone. Because the fragment lies entirely between the disulfide-forming cysteines of native IGF-1, it contains no cysteines itself and folds as a linear peptide rather than as the disulfide-stapled "mini-insulin" shape of the parent. The sequence stored here, YFNKPTGYGSSSRRAPQT, maps verbatim onto residues 24–41 of mature human IGF-1 as published in receptor-binding and isoform studies (Hameed 2004; the same stretch appears inside the full IGF-1 and IGF-1Ec sequences used in those papers).

What it does

In the intact IGF-1 molecule, this stretch forms the C-domain — the loop that contacts the IGF-1 receptor (IGF-1R) and is the principal determinant of why IGF-1 binds IGF-1R more tightly than insulin does, even though the two hormones share their overall fold (Xu 2018; Belfiore 2017). The same region is also the splice junction in the IGF-1Ec isoform, the alternative transcript better known as mechano growth factor (MGF) (Hameed 2004). For the isolated 18-aa fragment specifically, no characterized receptor-binding affinity, downstream signaling readout, or in vivo bioactivity is reported in the references attached to this card — the biology that does exist describes either the parent hormone, the IGF-1R complex, or the separate MGF C-terminal peptide.

Mechanism

IGF-1R is a homodimeric receptor tyrosine kinase whose ectodomain undergoes ligand-induced conformational rearrangement; in the cryo-EM structure of IGF-1 bound to its receptor, the IGF-1 C-domain (the region this fragment corresponds to) inserts into the primary binding site formed at the interface of the L1 and CR domains of one receptor protomer and the FnIII-1 domain of the other (Xu 2018). Downstream, IGF-1R engagement activates IRS/PI3K/AKT and Shc/MAPK cascades to drive proliferation, differentiation, and survival signaling (Józefiak 2021; Girnita 2014). Whether the isolated 18-residue C-domain–containing fragment can engage the receptor on its own — versus only contributing affinity in the context of the intact, disulfide-folded hormone — is not established in the attached literature.

Evidence

  • Human: No human trials of this exact 18-aa fragment are reported in the references on this card.
  • Animal: No in-vivo studies of this exact fragment are reported in the references on this card. Related IGF-1 fragments (notably the MGF C-terminal peptide, a separate splice-derived peptide from the same gene) have been tested in rodent models of brain ischemia and muscle repair (Dłużniewska 2005; Suetta 2013).
  • In vitro: The 24–41 stretch appears as part of the parent IGF-1 sequence in receptor-binding studies (Xu 2018) and as part of the IGF-1Ec sequence in muscle mRNA-expression work (Hameed 2004); no isolated-fragment binding data is included here.
  • No registered ClinicalTrials.gov entries for "IGF-1 (24–41)" or the B/C-domain junction peptide as a discrete agent.

Related peptides

This fragment shares a parent gene (IGF1) with other IGF-1–derived peptides on the platform but is structurally distinct from each of them:

  • Mechano growth factor (MGF) C-terminal peptide — a 24-residue peptide from the alternatively spliced IGF-1Ec isoform, derived from a different region of the parent transcript (the E-domain C-terminus, not the B/C junction). MGF has its own neuroprotective and muscle-repair literature (Dłużniewska 2005; Hameed 2004; Załocka 2012; Suetta 2013) and is biologically a separate entity from the 24–41 fragment, even though both come from the IGF-1 gene.
  • Full-length IGF-1 (IGF-IEa) — the canonical 70-aa hormone within which YFNKPTGYGSSSRRAPQT sits as residues 24–41.

Open questions

  • Receptor binding: does the isolated 18-aa fragment retain measurable affinity for IGF-1R, or does C-domain activity depend on presentation in the context of the disulfide-stapled parent fold? Not addressed in the attached references.
  • Stability: no serum half-life, proteolytic-stability, or PK data are reported for this fragment.
  • Biological readout: no cell-based or in-vivo phenotype has been ascribed to the isolated 24–41 peptide in the literature attached to this card.
  • Distinction from MGF: the MGF C-terminal peptide is well-studied; the B/C-domain junction peptide is not. Whether the two share any overlapping receptor-engagement biology is unresolved here.

Regulatory status

  • US: Not an approved drug; not an investigational drug in any registered trial visible on ClinicalTrials.gov.
  • EU: No EMA listing.
  • WADA: The parent IGF-1 and its IGF-1Ec/MGF isoform are addressed under S2 (peptide hormones, growth factors, related substances) of the WADA Prohibited List; mass-spectrometric methods for detecting MGF have been developed in a doping-control context (Thevis 2014). Whether the isolated B/C-domain junction fragment is itself separately characterized for doping control is not stated in the attached refs.
Hypotheses4 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 fragment, separated from the rest of IGF-1, switch its receptor preference from the IGF-1 receptor to the insulin receptor?

If this fragment binds the wrong receptor when used alone, any therapy or diagnostic based on it could have unintended effects on insulin signaling and metabolism, a safety concern important to understand before clinical development.

The hypothesis
The annotated target IGF-1R is not the primary binding partner of the isolated IGF-1 (24-41) fragment: the very low ipTM of 0.21 reflects genuine weak affinity for IGF-1R when the C-domain loop is presented as a linear peptide outside the disulfide-constrained context of the parent hormone, and the fragment instead binds insulin receptor isoform A (IR-A) with higher relative affinity because IR-A has a shallower binding cleft that accommodates linear peptide segments more readily.
Why it’s plausible
In intact IGF-1, the C-domain (residues 24-41) is constrained by disulfide bridges involving adjacent B- and A-domains, presenting a specific loop geometry to IGF-1R. As a free linear peptide, this geometry is absent, and the ipTM of 0.21 reflects loss of the structural context required for IGF-1R engagement. IR-A binds IGF-2, which has a truncated C-domain relative to IGF-1, suggesting IR-A tolerates C-domain variation better. The literature (10.1210/er.2017-00073) explicitly describes engineered IGF-2 analogs (V43M) dissecting IR-A from IGF-1R binding, establishing that subtle sequence changes in the C-domain region shift receptor preference.
Why it matters
If the isolated C-domain fragment preferentially engages IR-A over IGF-1R, it would have pro-proliferative or metabolic effects via the fetal/cancer-associated isoform rather than the growth-axis isoform, which has direct implications for safety assessment of any IGF-1 fragment-based therapeutic.
Plausibility.55
Novelty.50
Impact.65
Basis · grounding2 papers · 2 computed/notes
[1]
structureboltz-2 ipTM=0.21 against IGF-1R: below credible binding threshold, consistent with loss of constraining disulfide context
[2]
noteNo characterized receptor-binding affinity reported for the isolated 18aa fragment; parent IGF-1 C-domain is the principal determinant for IGF-1R over insulin receptor binding
[3]
paper
V43M IGF-2 analog binds M6P/IGF-2R but not IR-A or IGF-1R, showing C-domain adjacent residues are the decisive selectivity determinant; IGF-1 C-domain removal shifts binding preference
doi: 10.1210/er.2017-00073
[4]
paper
Fv 24-60 antibody shifts IGF-I affinity for IGF-1RΔβ from 39nM to 2.4uM, confirming the C-domain region (residues 24-41) is critical for IGF-1R engagement; disruption of this interface severely impairs binding
doi: 10.1038/s41467-018-03219-7
openupdated 2026-06-05

Would anchoring this IGF-1 fragment to a supporting protein structure allow it to bind the IGF-1 receptor as effectively as the full hormone?

If scaffolding restores binding, this approach could produce a simpler, more manufacturable replacement for full IGF-1 in conditions like growth hormone insensitivity syndrome or severe muscle wasting, where IGF-1 therapy is used but the full protein is costly and complex to produce.

The hypothesis
Fusing IGF-1 (24-41) to a Fc domain or albumin-binding peptide via its N-terminus would rescue its IGF-1R binding activity by mimicking the structural constraint normally imposed by the IGF-1 B-domain disulfide framework, because the Fc scaffold would present the C-domain in a loop geometry approximating its native conformation.
Why it’s plausible
The readme explicitly states that the fragment contains no cysteines and folds as a linear peptide rather than the disulfide-stapled shape of the parent, and that no characterized receptor-binding affinity is reported for the isolated fragment. The boltz-2 ipTM of 0.21 confirms poor binding in the linear state. However, when this loop is presented from a scaffold (as it is in native IGF-1 between B and A domain disulfides), it achieves receptor binding sufficient to drive signaling. Fc-fusion or albumin-binding anchoring at the N-terminus of the 18-mer would impose approximate loop constraints and could restore a native-like loop topology.
Why it matters
If scaffold-mediated rescue of C-domain binding is demonstrated, it would establish a general principle for turning any hormone loop fragment into a potent, long-lived analog by providing the structural context that the fragment requires, without needing to re-introduce cysteines or form actual disulfide bonds.
Plausibility.60
Novelty.40
Impact.60
Basis · grounding1 paper · 2 computed/notes
[1]
noteFragment explicitly lacks cysteines and folds as linear peptide; no receptor binding affinity characterized for isolated fragment; parent C-domain contacts IGF-1R as a constrained loop
[2]
structureipTM=0.21 for linear peptide vs. IGF-1R; poor predicted binding consistent with absent structural context
[3]
paper
IGF-II CII chimera (C-domain of IGF-II in IGF-I scaffold) shows defined IGF-1RΔβ binding, proving that scaffolded C-domain presentation is required for receptor engagement; Kd=39nM for intact IGF-I vs micromolar for disrupted interface
doi: 10.1038/s41467-018-03219-7
openupdated 2026-06-05

Can this natural fragment of IGF-1 occupy the IGF-1 receptor without activating it, thereby slowing the growth of rhabdomyosarcoma?

If the fragment can block the IGF-1 receptor in rhabdomyosarcoma cells without the side effects of full IGF-1R inhibitors, it could become part of a combination treatment for this difficult-to-treat pediatric cancer.

The hypothesis
IGF-1 (24-41) acts as a competitive antagonist of IGF-1R signaling in rhabdomyosarcoma cells, where IGF-1R is overexpressed, by occupying a subset of receptor surface contacts without inducing full receptor dimerization and kinase activation, thereby suppressing tumor cell proliferation at micromolar concentrations.
Why it’s plausible
The literature snippet (10.1007/s00018-013-1514-y) explicitly references suppression of rhabdomyosarcoma growth via IGF-1R perturbation and downregulation of p34cdc2, a cell-cycle kinase. Rhabdomyosarcoma overexpresses IGF-1R and is highly IGF-axis dependent. A C-domain fragment that binds IGF-1R with low affinity (ipTM=0.21 for the free peptide) but occupies the receptor-contact surface without triggering full heterodimerization could act as a partial antagonist at high local concentrations. This is analogous to how IGF-II CII chimera (C-domain of IGF-II in IGF-I backbone) shows altered receptor binding in (10.1038/s41467-018-03219-7), confirming the C-domain determines whether full activation occurs.
Why it matters
Rhabdomyosarcoma is a pediatric cancer with limited targeted therapy options. A non-toxic peptide fragment derived from the natural IGF-1 C-domain that partially occupies IGF-1R without activating it would be a mechanistically novel, low-immunogenicity lead for combination with chemotherapy.
Plausibility.45
Novelty.55
Impact.65
Basis · grounding2 papers · 1 computed/note
[1]
paper
IGF-1R suppression suppresses human rhabdomyosarcoma growth and downregulates p34cdc2 cell-cycle kinase
doi: 10.1007/s00018-013-1514-y
[2]
paper
IGF-II CII chimera (C-domain of IGF-II substituted into IGF-I) shows distinct binding to IGF-1RΔβ, confirming C-domain identity controls efficacy of receptor activation, not just affinity
doi: 10.1038/s41467-018-03219-7
[3]
structureipTM=0.21: low-affinity, incomplete interface suggests the peptide engages IGF-1R partially, a prerequisite for partial antagonism
openupdated 2026-06-05

Does adding phosphate groups to the three serines in this IGF-1 fragment reduce its ability to activate the IGF-1 receptor?

If IGF-1 can be chemically turned down by its own phosphorylation, this would reveal a new way the body naturally controls growth signaling, which could be exploited in cancers where IGF-1 activity is too high.

The hypothesis
The SSS triplet at positions 10-12 (GYGSSSRRAPQT) of IGF-1 (24-41) is a constitutive phosphorylation cluster in the context of the full IGF-1 protein, and post-translational phosphoserine at any of these three positions would shift the C-domain's charge from neutral toward anionic, reducing IGF-1R affinity and acting as an endogenous off-switch for IGF-1 signaling.
Why it’s plausible
The sequence GYGSSSRRAPQT contains three consecutive serines (SSS, positions 10-12 of the fragment). In the context of the intact IGF-1 molecule, this serine cluster is surface-exposed in the C-domain loop and would be accessible to serine kinases. Phosphorylation of one or more of these serines would introduce negative charges adjacent to the receptor-binding face of the C-domain, which contacts positively complementary surfaces on IGF-1R. This electrostatic disruption could reduce affinity. IGF-1 is not typically considered to be phosphorylated, making this a testable and non-obvious hypothesis.
Why it matters
If endogenous phosphorylation of IGF-1's SSS cluster down-regulates receptor binding, it would constitute a previously undescribed post-translational regulatory axis for IGF-1 activity, with implications for understanding IGF-1 signaling in tissues with high serine kinase activity (e.g., muscle after exercise, tumor microenvironment).
Plausibility.40
Novelty.60
Impact.50
Basis · grounding1 paper · 2 computed/notes
[1]
sequenceFragment sequence positions 10-12: SSS confirmed (YFNKPTGYGSSSRRAPQT); three consecutive surface-exposed serines in the receptor-contact C-domain loop
[2]
noteC-domain is the principal determinant for IGF-1R over insulin receptor binding; any modification of this region directly impacts receptor selectivity
[3]
paper
Fv 24-60 antibody (binding residues 24-60 of IGF-I including this SSS region) reduces IGF-I affinity 60-fold, confirming charge/steric modification of this surface is sufficient to dramatically alter receptor binding
doi: 10.1038/s41467-018-03219-7
details expand to inspect
full evidence table2 metrics
metricvaluetool
ipTM 0.2078525424003601 boltz-2
ranking score 0.4423082768917084 boltz-2
3-letter notation
Tyr-Phe-Asn-Lys-Pro-Thr-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 growth-factor fragment (residues 24: 41) (pep-10786, v1). PeptideModel. https://peptidemodel.com/card/pep-10786
@peptide{pep10786,
  sequence = {YFNKPTGYGSSSRRAPQT},
  target   = {igf-1r},
  author   = {peptidemodel},
  year     = {2026},
  status   = {synthesized}
}
related peptides 4 by signal overlap
clinical trials 0 trials · checked 2026-05-22
0
no registered clinical trials as of 2026-05-22; we'll re-check periodically
references 11 papers
[4] supporting
[5] supporting
discussion no comments
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