Lab-made VIP hormone copy (CHEMBL3102926)
An experimental copy of VIP, a natural body signal that relaxes smooth muscle in the gut, lungs, and brain; 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
CHEMBL3102926 is a 28-residue synthetic analog of vasoactive intestinal peptide (VIP) — a naturally occurring hormone and neuropeptide first isolated from porcine duodenal extracts by Said and Mutt in 1970. VIP is present throughout the gut, brain, and lungs, where it controls smooth-muscle tone, immune activity, and glandular secretion. This analog was designed as a research tool: its sequence carries several substitutions relative to native VIP and a two-residue C-terminal extension (Gly-Lys) that facilitates peptide synthesis and chromatographic purification. The stored sequence (HSDAVFTDNYTRRKQAVKKYLNSILNGK) does not carry the C-terminal amide that native VIP bears; the Gly-Lys tail replaces the amidated asparagine that caps the endogenous peptide's C-terminus. ChEMBL records an EC50 of 1.37 nM at the VPAC1 receptor, placing its potency in the low-nanomolar range typical of VIP-class ligands (ChEMBL3102926).
What it does
VIP acts through two closely related receptors, VPAC1 and VPAC2, which are found on immune cells, smooth muscle, airway epithelium, liver, and neurons. VPAC1 is the predominant subtype on resting monocytes, macrophages, and lung tissue. When a VIP-class ligand binds VPAC1, it activates a Gs protein that stimulates adenylyl cyclase, raising intracellular cyclic AMP (cAMP); the resulting PKA and Epac signaling suppresses pro-inflammatory cytokines such as IL-6 and TNF-α while promoting the anti-inflammatory mediator IL-10. This analog's low-nanomolar VPAC1 potency means it can engage that pathway at concentrations similar to native VIP.
The Giordanetto and colleagues (ACS Medicinal Chemistry Letters, 2013) study that characterized this compound's parent scaffold was principally aimed at VPAC2, which mediates glucose-dependent insulin secretion from pancreatic β-cells — a target of interest for type-2 diabetes pharmacology. The parent paper used the M17I / Gly-Lys-extended backbone as a reference point for stapled cyclic analogs; VPAC1 potency data for this specific compound appear in the ChEMBL bioassay record rather than in the publication's main tables.
Evidence
- Human: No human data. This is a biochemical research compound; no clinical studies have been conducted with CHEMBL3102926.
- Animal: No in vivo data reported for this specific analog.
- In vitro: EC50 = 1.37 nM at the human VPAC1 receptor in a cAMP functional assay (ChEMBL3102926). The parent compound class (stapled VIP derivatives tested by Giordanetto and colleagues, 2013) showed sub-nanomolar VPAC2 potency and enhanced glucose-dependent insulin secretion in isolated pancreatic islets compared with native VIP.
Mechanism
VPAC1 (gene name VIPR1) is a class B G protein-coupled receptor (GPCR). Agonist binding engages the N-terminal ectodomain first, positioning the peptide's C-terminal helix against the transmembrane bundle; together, these contacts activate the Gs heterotrimer. Adenylyl cyclase stimulation raises cAMP, which activates both protein kinase A (PKA) and the exchange protein Epac. PKA phosphorylates CREB and other transcription factors linked to anti-inflammatory gene programs; Epac activates Rap1 GTPase. In immune cells, this pathway inhibits NF-κB-driven cytokine release. In bronchial smooth muscle, elevated cAMP promotes relaxation. VIP and its analogs also bind VPAC2 (gene VIPR2) with comparable affinity; selectivity between the two subtypes requires specific substitutions at positions 11, 22, and 28 of the VIP sequence (Giordanetto and colleagues, 2013 context; Nicole and colleagues, 2000 alanine-scanning work).
Open questions
- Whether the Gly-Lys C-terminal extension meaningfully alters VPAC1 vs VPAC2 selectivity relative to native VIP has not been characterized in the published literature.
- Proteolytic stability of this analog in plasma has not been reported.
- No in vivo pharmacokinetic or efficacy data exist.
- The relationship between the EC50 measured at VPAC1 and VPAC2 for this specific compound has not been published; it is unclear whether the GK tail shifts the VPAC1/VPAC2 potency ratio.
Related peptides
- Native VIP (aviptadil) — the endogenous 28-residue parent peptide with C-terminal amide and Met-17; FDA Orphan Drug status for ARDS and pulmonary arterial hypertension.
- [Ala11,22,28]-VIP — a triple-substituted VIP analog with >1,000-fold VPAC1 selectivity over VPAC2, developed by Nicole and colleagues (2000) as a selective pharmacological probe.
- BAY 55-9837 — a 32-residue VPAC2-selective analog used to dissect the insulin-secretory role of VPAC2 from VPAC1-mediated hepatic glucose production.
▸full evidence table1 metrics
| metric | value | tool |
|---|---|---|
| EC50 | 1.37 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{pep10481,
sequence = {HSDAVFTDNYTRRKQAVKKYLNSILNGK},
target = {vpac1},
author = {peptidemodel},
year = {2026},
status = {bioassayed}
}