pe
pep-10477 v1 CC-BY-SA-4.0

VIP hormone copy: relaxes blood vessels, calms inflammation (research peptide, code CHEMBL3102922)

A lab-made version of a natural body hormone (called VIP) that widens blood vessels, helps control insulin, and quiets inflammation. Used only as a research tool, not a medicine.

statusbioassayed targetVPAC1 length30 aa refs1
status 5 / 5
prediction metrics openfold3-mlx 0.3.1
ipTM0.840
pTM0.709
avg pLDDT48.3
ranking score0.908
STRUCTURE · PEP-10477 × VPAC1
ranking0.908
target interface 4.5Å peptide drag rotate · ctrl+scroll zoom · right-click pan
openfold3-mlx 0.3.1 · mmCIF ↓ download
sequence30 aa
151015202530
HSDAVFTDNYTRLRK QIAVKEYLNKILNGK
overview readme

What this is

This is a 30-amino-acid analog of vasoactive intestinal peptide (VIP), a hormone made by nerves and gut cells that relaxes blood vessels and smooth muscle, helps regulate insulin release, and acts as an anti-inflammatory signal in the immune system. The molecule is catalogued in the ChEMBL bioactivity database under identifier CHEMBL3102922 and was reported by Giordanetto and colleagues (ACS Medicinal Chemistry Letters, 2013) as part of a series of VIP derivatives designed to be more drug-like than the natural 28-residue peptide. It is a research compound — not a marketed drug — used to study how VIP-family receptors respond to engineered changes in the peptide backbone.

What it does

Native VIP binds two closely related class B G-protein-coupled receptors, VPAC1 and VPAC2. Both receptors couple to Gαs and raise intracellular cAMP when activated (Couvineau and colleagues, Frontiers in Endocrinology, 2012). Through this signaling, VIP causes vasodilation, smooth-muscle relaxation in the gut and airway, glucose-dependent insulin secretion from pancreatic β-cells, and a shift of T-cell populations toward anti-inflammatory phenotypes. This analog was characterized as a cAMP-stimulating agonist in cells expressing a human VIP-family receptor (Giordanetto and colleagues, 2013); the same family of designed analogs in that study showed sub-nanomolar potency in glucose-dependent insulin-secretion assays in MIN6 β-cells.

Mechanism

The stored sequence HSDAVFTDNYTRLRKQIAVKEYLNKILNGK is a 30-mer derived from native human VIP (HSDAVFTDNYTRLRKQMAVKKYLNSILN, 28 aa) with three internal substitutions (M17→I, K20→E, S25→K) and a C-terminal Gly-Lys (GK) extension. Giordanetto and colleagues (2013) used the I17-VIP-GK template as a reference scaffold for their series; the I17 substitution and GK tag improve handling and assay behavior versus the native sequence, and the K20/S25 positions correspond to the i, i+4 register exploited in their lactamized and olefin-stapled analogs to stabilize the receptor-bound α-helix. The 30-residue analog therefore captures the helical pharmacophore that engages the receptor extracellular domain and transmembrane bundle of class B GPCRs as described for VPAC1 (Couvineau and colleagues, 2012), with side-chain changes intended to bias secondary structure toward the active conformation.

Evidence

  • In vitro: ChEMBL bioassay record CHEMBL3102922 reports EC50 = 0.21 nM for cAMP accumulation in CHO Flp-in cells expressing a human VIP-family receptor, measured by TR-FRET, with the source publication being Giordanetto and colleagues (ACS Medicinal Chemistry Letters, 2013). That paper situates this compound within a series whose lead stapled and lactamized analogs showed improved helical content, protease stability, and insulinotropic potency relative to native VIP in MIN6 β-cell assays.
  • Animal: No in vivo studies of this specific 30-mer are present in the dossier sources.
  • Human: No human studies.

Regulatory status

This is a research-grade compound. It has no FDA or EMA approval and no marketing authorization in any jurisdiction. It is not a controlled substance.

Related peptides

  • VIP itself and other VIP-family analogs share the same receptors (VPAC1 and VPAC2) and the same general mechanism of cAMP elevation. Related research analogs from the same medicinal-chemistry program target VPAC2 for glucose-dependent insulin secretion (Giordanetto and colleagues, 2013).
  • PACAP (pituitary adenylate cyclase-activating peptide) is the other endogenous high-affinity ligand for VPAC1 and VPAC2 (Couvineau and colleagues, 2012).
details expand to inspect
full evidence table1 metrics
metricvaluetool
EC50 0.21 nM GPCRDB/ChEMBL
structural qualityopenfold3
0
metricvaluenote
gpde0.807global PDE — lower = better
disorder0.189fraction disordered
chain pair ipTM (A, B)0.840interface quality
3-letter notation
His-Ser-Asp-Ala-Val-Phe-Thr-Asp-Asn-Tyr-Thr-Arg-Leu-Arg-Lys-Gln-Ile-Ala-Val-Lys-Glu-Tyr-Leu-Asn-Lys-Ile-Leu-Asn-Gly-Lys
recipeopenfold3-mlx 0.3.1
parametervalue
modelopenfold3-mlx 0.3.1
weightsaedd8f3eb814e392…
hardwareapple_m4_base_16gb
mlx version0.31.1
python3.14.3
random seed42
msa strategycolabfold
diffusion samples1
runtime409s
predicted bymlx@peptide
predicted at2026-04-24
python3 openfold3/run_openfold.py predict --query_json {query.json} --runner_yaml examples/example_runner_yamls/mlx_runner.yml --output_dir {output_dir} --num_diffusion_samples 1
citationbibtex
peptidemodel (2026). VIP hormone copy: relaxes blood vessels, calms inflammation (research peptide, code CHEMBL3102922) (pep-10477, v1). PeptideModel. https://peptidemodel.com/card/pep-10477
@peptide{pep10477,
  sequence = {HSDAVFTDNYTRLRKQIAVKEYLNKILNGK},
  target   = {vpac1},
  author   = {peptidemodel},
  year     = {2026},
  status   = {bioassayed}
}
related peptides 5 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 1 papers
discussion no comments
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