Valosin (VQY): gut peptide in the glucagon family
A small peptide first found in pig intestine in 1985, part of the same family as glucagon. It acts on the gut and is used as a lab research tool, not an approved 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
Valosin (also written VQY from its first three residues) is a 25-amino acid peptide first isolated from porcine intestinal tissue in 1985. It belongs to the glucagon peptide superfamily and is classified on this platform under the glucagon receptor (GCGR), a class B GPCR that is a target of next-generation multi-agonist obesity drugs. The original isolation paper described biological activity on the gastrointestinal tract of dogs (Schmidt and colleagues, FEBS Letters, 1985). Chemical synthesis of the full 25-residue sequence was reported shortly after (AKAJI and colleagues, Chemical and Pharmaceutical Bulletin, 1987). Valosin is primarily known today as the eponymous peptide embedded in the precursor of valosin-containing protein (VCP/p97), the major mammalian AAA-ATPase — the protein takes its name from the original porcine intestinal peptide.
History
Valosin was isolated from porcine intestine and characterized by Schmidt and colleagues in 1985 (FEBS Letters). At the time of isolation, no structural homology to known proteins or nucleotide sequences was found. The discovery report noted preliminary evidence of biological effects on the dog gastrointestinal tract. The following year, Koller and colleagues (Nature, 1987) used a cDNA clone to identify the precursor protein that contained the valosin sequence; that precursor protein — a large, ubiquitously expressed AAA-ATPase — subsequently became known as valosin-containing protein (VCP), or p97. Total chemical synthesis of the valosin 25-residue sequence was confirmed by AKAJI and colleagues (Chemical and Pharmaceutical Bulletin, 1987), establishing the sequence identity and enabling pharmacological study.
What it does
The 1985 isolation report identified gastrointestinal biological activity in dog models (Schmidt and colleagues, 1985), though detailed receptor-level pharmacology of the valosin peptide itself has not been extensively characterized in the published literature. The platform assigns GCGR (glucagon receptor) as the primary target, consistent with valosin's classification in the glucagon superfamily based on structural relatedness. Most subsequent research on "valosin-containing protein" has concerned the VCP/p97 AAA-ATPase — a distinct and far larger molecular entity — rather than the valosin peptide itself.
Evidence
- Human: No human clinical trials of the valosin peptide have been published.
- Animal: Preliminary biological activity on the gastrointestinal tract reported in dog models at the time of the original isolation (Schmidt and colleagues, FEBS Letters, 1985). No subsequent controlled animal studies of the isolated peptide identified in this dossier.
- In vitro: No in vitro receptor binding or functional assay data for the valosin peptide are present in this dossier.
Known effects
- Gastrointestinal biological activity in dog models (Schmidt and colleagues, 1985) — evidence level: single observation from isolation report
Regulatory status
- US / EU: Not approved, not an investigational drug. Research-characterized peptide only.
- WADA: No restrictions identified.
Related peptides
- Glucagon — endogenous GCGR agonist; prototype ligand for the same receptor family (/card/pep-04430)
- Retatrutide — synthetic tri-agonist (GLP-1R / GIPR / GCGR) in clinical development for obesity; the GCGR component shares the receptor targeted by valosin's classification
Mechanism
Valosin is a 25-residue peptide whose sequence begins Val-Gln-Tyr (VQY), placing it in the glucagon superfamily. The precursor protein identified by Koller and colleagues (Nature, 1987) is the source of the VCP/p97 AAA-ATPase name — the large cytosolic ATPase takes its name from containing the valosin sequence, though VCP/p97 itself (a ~97 kDa hexameric unfoldase) has no connection to gastrointestinal or GCGR biology. Receptor-level pharmacology of the isolated valosin peptide at GCGR — binding affinity, cAMP induction, GLP-1R cross-reactivity — has not been reported in the literature captured in this dossier.
Open questions
- Receptor-level characterization of valosin at GCGR (and potentially GLP-1R, given structural relatedness) has not been published; whether valosin acts as a full agonist, partial agonist, or weak binder at GCGR is unknown
- The relationship between the valosin peptide and the large body of VCP/p97 biology (protein quality control, autophagy, ubiquitin-chain processing) is one of nomenclature only — whether the valosin sequence within the VCP precursor has any intrinsic signaling role has not been explored
- Human ortholog and cross-species conservation of the valosin sequence relative to the porcine source have not been characterized in the dossier sources
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.
Does valosin actually work through the glucagon receptor, or does it act on a different gut receptor to produce the digestive effects seen in dogs?
Knowing the real receptor target could reveal a new signaling pathway controlling gut motility or secretion, with implications for treatments of irritable bowel syndrome or gastroparesis.
Does valosin bind the glucagon receptor without fully switching it on, and if so, does it favor one signaling pathway over another?
If true, valosin could provide a natural blueprint for drugs that tune the glucagon receptor more selectively, potentially reducing side effects of current metabolic medicines. Patients with obesity or diabetes might eventually benefit from treatments built on this kind of partial signal.
Does the tyrosine at position 3 of valosin act like the missing histidine that other glucagon-family peptides use to activate their receptor?
If a tyrosine can replace histidine at this critical position, chemists could design more stable glucagon-related drug candidates that avoid known problems with histidine-containing peptides, such as sensitivity to chemical degradation.
Could valosin naturally limit how strongly glucagon raises blood sugar, and could a drug based on it do the same more safely than current approaches?
If true, this could point to a gentler way to lower blood glucose in type 2 diabetes without the risk of blocking glucagon so completely that dangerous side effects arise. People with diabetes could benefit from a new kind of therapy with a wider safety margin.
Could the small valosin peptide, which is naturally embedded in a larger protein called VCP, disrupt or tune VCP's function when applied from outside the cell?
VCP is overactive in several cancers and protein-misfolding diseases. If valosin can dampen its activity, it might open a new class of biologics targeting conditions from multiple myeloma to a rare genetic muscle disease called IBMPFD.
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.7708308696746826 | boltz-2 |
| ranking score | 0.7825126051902771 | boltz-2 |
▸structural qualityopenfold3
| metric | value | note |
|---|---|---|
| gpde | 0.907 | global PDE — lower = better |
| disorder | NaN | fraction disordered |
▸3-letter notation
▸recipeboltz-2 1.0
| parameter | value |
|---|---|
| model | boltz-2 1.0 |
| weights | — |
| hardware | nvidia_nim_api |
| mlx version | — |
| python | — |
| random seed | — |
| msa strategy | none |
| diffusion samples | 1 |
| runtime | — |
| predicted by | mlx@peptide |
| predicted at | 2026-04-24 |
▸citationbibtex
@peptide{pep10682,
sequence = {VQYPVEHPDKFLKFGMTPSKGVLFY},
target = {gcgr},
author = {peptidemodel},
year = {2026},
status = {designed}
}