Blood-vessel-relaxing VIP peptide (CHEMBL3102923)
A lab-engineered fragment of VIP, a natural nerve-and-gut hormone that relaxes blood vessels and reduces inflammation; used only as a lab research tool.
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 17-amino-acid analog of vasoactive intestinal peptide (VIP), a hormone released 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 CHEMBL3102923 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. The stored sequence RKQKAVKKYLNSILNGK represents the bare peptide backbone; the active molecule in the Giordanetto series carries a lactam staple (a side-chain-to-side-chain amide crosslink) that is absent from the raw sequence shown here.
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 17-mer analog was characterized as a VPAC1 agonist (ChEMBL CHEMBL3102923) with EC50 = 1.16 nM; the same series of designed analogs reported by Giordanetto and colleagues (2013) showed sub-nanomolar potency and improved glucose-dependent insulin secretion in pancreatic islet assays for the lead stapled variants.
Mechanism
The sequence RKQKAVKKYLNSILNGK spans the C-terminal half of the native VIP sequence (approximately residues 15–28 of the 28-residue peptide), plus a C-terminal Gly-Lys (GK) extension. Compared with native VIP at that region, the sequence contains a Met→Lys substitution that introduces a second lysine available for lactam bond formation. Giordanetto and colleagues (2013) employed an i, i+4 lactamization strategy — forming a covalent amide bridge between the side chains of a lysine and glutamic acid four residues apart — to stabilize the α-helical conformation the peptide adopts on receptor binding. Reinforcing the helix is important because VIP and its analogs interact with VPAC receptors via a two-site mechanism: the central and C-terminal portion of the peptide docks on the large extracellular N-terminal domain of the receptor, while the N-terminus of the ligand engages the transmembrane bundle to trigger cAMP production through Gαs (Couvineau and colleagues, 2012). Being only a C-terminal fragment, this 17-mer lacks the full VIP N-terminus; it represents the helix-stabilized receptor-docking domain rather than a full agonist scaffold.
Evidence
- In vitro: ChEMBL bioassay record CHEMBL3102923 reports EC50 = 1.16 nM at the VPAC1 receptor, with the source publication being Giordanetto and colleagues (ACS Medicinal Chemistry Letters, 2013). That paper characterized a series of lactam-stapled and hydrocarbon-stapled VIP analogs and showed that stapling at the 13–17 position of VIP improved α-helical content and modulated receptor potency; the most potent hydrocarbon-stapled analog reached EC50 = 0.049 nM at VPAC2 (Giordanetto and colleagues, 2013).
- Animal: No in vivo studies of this specific 17-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
- pep-10477 — a 30-mer VIP analog from the same Giordanetto 2013 series (CHEMBL3102922, EC50 = 0.21 nM), representing a full-length scaffold from the same medicinal-chemistry program.
- PACAP (pituitary adenylate cyclase-activating polypeptide) is the other endogenous high-affinity ligand for VPAC1, sharing the same Gαs/cAMP signaling axis (Couvineau and colleagues, 2012).
▸full evidence table1 metrics
| metric | value | tool |
|---|---|---|
| EC50 | 1.16 nM | GPCRDB/ChEMBL |
▸3-letter notation
▸recipeboltz-2 2.2.1
| parameter | value |
|---|---|
| model | boltz-2 2.2.1 |
| weights | — |
| hardware | vast_v100_32gb |
| mlx version | — |
| python | — |
| random seed | 1 |
| msa strategy | colabfold_local |
| runtime | — |
| predicted by | — |
| predicted at | 2026-05-22 |
▸citationbibtex
@peptide{pep10478,
sequence = {RKQKAVKKYLNSILNGK},
target = {vpac1},
author = {peptidemodel},
year = {2026},
status = {bioassayed}
}