pe
pep-10300 v1 CC-BY-SA-4.0

Vasopressin/oxytocin receptor-targeting peptide (CHEMBL1817756)

A small lab-made peptide that latches onto the vasopressin and oxytocin receptors, the body's controls for blood pressure, water balance, and social bonding. Research tool only, not a medicine.

statusbioassayed targetAVPR1A length7 aa refs1
status 5 / 5
prediction metrics boltz-2 2.2.1
ipTM0.975
pTM0.907
avg pLDDT82.8
ranking score0.858
STRUCTURE · PEP-10300 × AVPR1A
ranking0.858
target interface 4.5Å peptide drag rotate · ctrl+scroll zoom · right-click pan
boltz-2 2.2.1 · mmCIF ↓ download
sequence7 aa
157
CIQNCPG
in the news 2 articles
overview readme

What this is

CHEMBL1817756 is a 7-residue synthetic peptide (sequence CIQNCPG) catalogued in the ChEMBL bioactivity database as a ligand at the vasopressin/oxytocin receptor family. It is not a marketed drug and is not associated with a clinical program — it is a research-stage compound characterized in a medicinal-chemistry effort to design selective peptidic agonists of the V1a vasopressin receptor (Wiśniewski 2011). The two cysteines in the sequence indicate the molecule is designed to cyclize through a disulfide bridge, which is the canonical scaffold shared by vasopressin and oxytocin; that ring geometry is what allows binding to this receptor family at all.

What it does

In cell-based assays summarised in ChEMBL, CHEMBL1817756 binds the vasopressin V2 receptor with an EC50 of approximately 955 nM. The platform card also lists activity (or assay coverage) at V1a, V1b, and the oxytocin receptor, reflecting the cross-reactivity that is typical of compounds built on the vasopressin/oxytocin ring scaffold. The published series from which this compound is drawn was specifically aimed at producing V1a-selective, short-acting peptidic agonists for further pharmacological study (Wiśniewski 2011) — the compound is a probe of receptor pharmacology, not a therapeutic.

Evidence

  • Human: No human studies. This is a ChEMBL-catalogued research peptide; there are no clinical trials and no published in-vivo human data tied to this specific compound.
  • In vitro: Receptor-binding/functional activity at V2 (EC50 ≈ 955 nM) is documented in ChEMBL (CHEMBL1817756). The parent medicinal-chemistry series targeting V1a-selective short-acting agonists is described by Wiśniewski and colleagues (2011, Journal of Medicinal Chemistry).
  • Animal: None recorded in the dossier for this specific compound.

Related peptides

The vasopressin/oxytocin receptor family is one of the most extensively studied peptide-receptor systems in pharmacology. The clinically used members of this family are:

  • Vasopressin (/card/pep-04424) — the endogenous nonapeptide hormone (Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly-NH₂) that regulates water balance via V2 and vascular tone via V1a; ICU drug for vasodilatory shock and central diabetes insipidus.
  • Oxytocin — the closely related nonapeptide (differs from vasopressin at two positions) acting primarily at the oxytocin receptor.

CHEMBL1817756 sits in the same chemical neighbourhood — a disulfide-cyclised peptide acting at this receptor family — but is a research compound with low potency and no clinical role.

Hypotheses3 directions▾ collapse

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.

openupdated 2026-06-05

Does CIQNCPG last longer in blood than vasopressin because it lacks the site where enzymes normally cut the hormone apart?

Vasopressin infusions used in septic shock and surgery require continuous delivery because the hormone degrades in minutes. A more stable analog could work as a less frequent injection or even a patch, reducing intensive-care burden and improving outcomes for critically ill patients.

The hypothesis
The compact disulfide-cyclized scaffold of CIQNCPG confers substantially greater resistance to neprilysin and aminopeptidase cleavage than full-length vasopressin, making it a metabolically stable pharmacological tool for probing V1a-mediated cardiovascular responses in vivo at doses where native vasopressin is rapidly degraded.
Why it’s plausible
Vasopressin (9 aa, t1/2 in plasma ~10-20 min) is cleaved primarily at the Tyr2-Phe3 bond by neutral endopeptidase (neprilysin) and at the N-terminus by aminopeptidases. CIQNCPG presents no Tyr-Phe scissile bond; its 7-mer ring with Ile at position 2 removes the canonical neprilysin cleavage site. The cyclic constraint further shields backbone amides from aminopeptidase access. A more stable V1a-active peptide would extend the pharmacodynamic window in rodent cardiovascular or fluid-balance models.
Why it matters
Metabolically stable V1a agonists are sought for treatment of vasodilatory shock (septic shock, post-cardiac surgery hypotension) where repeated vasopressin infusion is limited by tachyphylaxis and short duration. A probe with longer in vivo residence would clarify V1a-specific contributions to hemodynamic recovery independent of V2-mediated antidiuresis.
Plausibility.65
Novelty.45
Impact.65
Basis · grounding1 paper · 2 computed/notes
[1]
sequenceCIQNCPG lacks Tyr-Phe at positions 2-3 (the primary neprilysin cleavage site in vasopressin); disulfide ring constrains N-terminal access for aminopeptidases
[2]
noteSeries goal: V1a-selective, short-acting peptidic agonists; 'short-acting' implies designers accepted some metabolic liability that could be improved
[3]
paper
Wisniewksi 2011 SAR campaign on substituted vasopressin/oxytocin scaffolds seeking V1a selectivity
doi: 10.1021/jm200278m
openupdated 2026-06-05

Could locking the peptide into a tighter double-ring structure using its terminal proline make it survive digestion and work as an oral medicine?

All existing vasopressin-type drugs must be injected or given as a nasal spray, which is inconvenient for long-term use. If this structural tweak leads to a tablet that reaches the bloodstream intact, it could transform treatment of conditions like low blood pressure disorders and nighttime bedwetting into a simple daily pill.

The hypothesis
The Pro7 C-terminus of CIQNCPG acts as a conformational brake that restricts the ring-tail dihedral and can be exploited as a handle for backbone N-methylation or macrolactamization to generate a bicyclic peptidomimetic with improved oral bioavailability without loss of receptor binding.
Why it’s plausible
Proline at the C-terminus of a cyclic peptide introduces a cis-trans isomerism around the preceding amide bond, which can lock the ring in a specific rotamer. In the context of a disulfide ring plus a C-terminal Pro, N-methylation of the Pro nitrogen or formation of a secondary macrolactam (head-to-tail cyclization through the Pro nitrogen) would yield a bicyclic structure with reduced amide bond exposure, lower polar surface area, and potential passive gut permeability. This strategy has been applied to cyclosporin-derived analogs and to Pro-terminated cyclic hexapeptides to improve cell permeability.
Why it matters
An orally bioavailable V1a modulator does not exist in the clinic. Current vasopressin analogs (desmopressin, terlipressin) require injection or intranasal delivery. A bicyclic derivative of CIQNCPG could serve as a first-in-class oral V1a-active scaffold for chronic indications such as Raynaud's phenomenon, nocturnal enuresis, or behavioral conditions linked to V1a signaling.
Plausibility.50
Novelty.60
Impact.65
Basis · grounding1 paper · 2 computed/notes
[1]
sequenceCIQNCPG terminates in Pro (position 7), introducing cis-trans isomerism at the Gly6-Pro7 amide; dual cyclization points (Cys1-Cys4 disulfide plus Pro7 tail) present a bicyclization opportunity
[2]
paper
N-methyl and N-methoxy glutamine substitutions tolerated in this scaffold family (compounds 22, 25), indicating the backbone accommodates N-substitution without catastrophic potency loss
doi: 10.1021/jm200278m
[3]
noteNo clinical program or oral formulation exists for this compound; current vasopressin therapeutics require non-oral delivery
openupdated 2026-06-05

Is the asparagine at position 5 the key switch that steers this peptide toward the V1a receptor and away from V2?

V1a and V2 receptors have opposite roles, V1a controls blood vessel tone and V2 regulates kidney water retention. A drug that cleanly separates them could treat hypertension or hemorrhage without the water-retention side effects that complicate current vasopressin therapies.

The hypothesis
The asparagine at position 5 of CIQNCPG (Asn5) is a selectivity determinant for V1a over V2, because V1a and V2 differ in a key second extracellular loop residue that forms a hydrogen bond with the ligand Gln/Asn side chain, and the shorter Asn side chain in this compact ring favors the V1a pocket geometry.
Why it’s plausible
The ChEMBL record shows measurable V2 activity (EC50 ~955 nM) yet the design goal of the Wisniewksi series was V1a selectivity. In the native vasopressin scaffold, Gln4 is a selectivity filter; N-substitutions on the glutamine amide in the published SAR reduced potency (compounds 23, 24, 26, 27 in doi:10.1021/jm200278m), while N-methyl and N-methoxy were tolerated without improving selectivity. CIQNCPG carries Asn rather than Gln at the equivalent ring position, introducing a one-methylene-shorter side chain that could relieve a steric clash specific to V2 while maintaining the H-bond.
Why it matters
Identifying Asn5 as a selectivity handle would rationalize why shorter acyl-amide substitutions are tolerated and open a targeted modification route: Asn5 analogs with varying side-chain length could systematically titrate V1a/V2 selectivity without disrupting the ring.
Plausibility.55
Novelty.55
Impact.60
Basis · grounding1 paper · 2 computed/notes
[1]
paper
N-substitutions on glutamine primary amide decrease potency at V1a/V2/OTR; N-methyl and N-methoxy tolerated but do not improve selectivity
doi: 10.1021/jm200278m
[2]
sequenceCIQNCPG has Asn at position 5, one methylene shorter than the Gln present in vasopressin at the equivalent ring position
[3]
noteCompound designed for V1a-selective agonism; shows measurable V2 activity (EC50 ~955 nM), implying incomplete selectivity
details expand to inspect
full evidence table1 metrics
metricvaluetool
EC50 954.99 nM GPCRDB/ChEMBL
3-letter notation
Cys-Ile-Gln-Asn-Cys-Pro-Gly
recipeboltz-2 2.2.1
parametervalue
modelboltz-2 2.2.1
weights
hardwarevast_v100_32gb
mlx version
python
random seed1
msa strategycolabfold_local
runtime
predicted by
predicted at2026-05-22
citationbibtex
peptidemodel (2026). Vasopressin/oxytocin receptor-targeting peptide (CHEMBL1817756) (pep-10300, v1). PeptideModel. https://peptidemodel.com/card/pep-10300
@peptide{pep10300,
  sequence = {CIQNCPG},
  target   = {avpr1a},
  author   = {peptidemodel},
  year     = {2026},
  status   = {bioassayed}
}
related peptides 2 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
[1]
New, Potent, Selective, and Short-Acting Peptidic V1aReceptor Agonists
Wiśniewski, K. et al. Journal of Medicinal Chemistry 2011
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