Lab-made fragment of VIP, a gut-relaxing hormone (CHEMBL3102924)
A short piece of vasoactive intestinal peptide (VIP), a natural gut hormone that relaxes smooth muscle and helps regulate blood flow. Used only as a research tool, not a medicine.
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.
What this is
This is a 13-amino-acid research peptide (sequence AVKKYLNSILNGK) cataloged in ChEMBL as a ligand for the VPAC1 receptor — one of the two main receptors for vasoactive intestinal peptide (VIP), a hormone made in the gut and nervous system that relaxes smooth muscle, regulates blood flow, and tunes immune signaling. The sequence corresponds to the C-terminal helical segment of native VIP (which is itself a 28-residue peptide first isolated from porcine intestine), extended by a short Gly-Lys tail. It is a tool compound from a structure-activity program on stapled VIP derivatives (Giordanetto et al., ACS Medicinal Chemistry Letters 2013), not a clinical drug.
What it does
VPAC1 is a class B G-protein-coupled receptor that, when activated by VIP, raises intracellular cAMP through Gαs coupling — the same general signaling family used by GLP-1, glucagon, and PACAP receptors. The full VIP peptide engages VPAC1 through two regions: the N-terminus, which drives receptor activation, and the central/C-terminal α-helix, which docks into the receptor's large N-terminal extracellular domain (Tan et al., Journal of Biological Chemistry 2007). This card's 13-mer covers only the C-terminal half of that helix, so on its own it represents the "anchor" portion of the VIP pharmacophore rather than a complete agonist scaffold.
History
VIP was originally isolated from porcine intestine and acts through two related class B G-protein-coupled receptors, VPAC1 and VPAC2, that share the same family as the receptors for PACAP, secretin, and GLP-1 (Giordanetto et al., ACS Medicinal Chemistry Letters 2013; Tan et al., Journal of Biological Chemistry 2007). Because native VIP binds both VPAC1 and VPAC2 with comparable potency, much of the medicinal chemistry around VIP has focused on building receptor-selective analogs and on stabilizing the bioactive C-terminal helix. Giordanetto and colleagues (2013) reported a series of olefin-stapled and lactam-bridged VIP derivatives aimed at VPAC2 selectivity and glucose-dependent insulin secretion as a candidate approach for type-2 diabetes; this card's 13-mer is one of the C-terminal sequences associated with that medicinal-chemistry program and was deposited in ChEMBL with a reported EC50 of 0.1 nM.
Evidence
- Human: No clinical trials of this specific 13-mer.
- Animal: No in vivo data in the dossier for this specific sequence.
- In vitro: ChEMBL records an EC50 of 0.1 nM at VPAC1 for this peptide (ChEMBL deposit linked to Giordanetto et al., ACS Medicinal Chemistry Letters 2013). The same medicinal-chemistry program characterized stapled VIP analogs primarily against VPAC2 and glucose-dependent insulin secretion in cell assays.
Related peptides
- VIP (vasoactive intestinal peptide) — the full-length 28-residue parent neuropeptide; this card's sequence overlaps its C-terminal helical region.
- PACAP (pituitary adenylate cyclase-activating polypeptide) — close paralog of VIP that shares VPAC1 and VPAC2 but also activates a third receptor (PAC1) with higher affinity.
- Stapled VIP analogs (Giordanetto 2013 series) — synthetic VIP derivatives with side-chain crosslinks designed to stabilize the C-terminal α-helix and improve metabolic stability and receptor potency.
▸full evidence table1 metrics
| metric | value | tool |
|---|---|---|
| EC50 | 0.1 nM | GPCRDB/ChEMBL |
▸structural qualityopenfold3
| metric | value | note |
|---|---|---|
| gpde | 0.789 | global PDE — lower = better |
| disorder | 0.185 | fraction disordered |
| chain pair ipTM (A, B) | 0.792 | interface quality |
▸3-letter notation
▸recipeopenfold3-mlx 0.3.1
| parameter | value |
|---|---|
| model | openfold3-mlx 0.3.1 |
| weights | aedd8f3eb814e392… |
| hardware | apple_m4_base_16gb |
| mlx version | 0.31.1 |
| python | 3.14.3 |
| random seed | 42 |
| msa strategy | colabfold |
| diffusion samples | 1 |
| runtime | 378s |
| predicted by | mlx@peptide |
| predicted at | 2026-04-24 |
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
@peptide{pep10479,
sequence = {AVKKYLNSILNGK},
target = {vpac1},
author = {peptidemodel},
year = {2026},
status = {bioassayed}
}