Dual pain-and-satiety research peptide (CHEMBL262172 / YGWDF)
A lab-made five-amino-acid molecule designed to act on both pain-signaling and gut-fullness pathways at once; 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 five-amino-acid peptide (YGWDF) that was made as part of a medicinal-chemistry effort to design a single molecule capable of engaging two different receptor systems at once — the opioid receptors (which handle pain signaling) and the cholecystokinin receptors (which handle satiety and gut signaling). It is not a drug, not a hormone, and not a wellness compound. It is a research ligand catalogued in ChEMBL as CHEMBL262172, drawn from a structure–activity series published by Agnes and colleagues (J. Med. Chem., 2006) that explored peptides built on overlapping pharmacophores at the opioid and cholecystokinin receptors.
History
The peptide comes from a 2006 paper in the Journal of Medicinal Chemistry titled "Structure–Activity Relationships of Bifunctional Peptides Based on Overlapping Pharmacophores at Opioid and Cholecystokinin Receptors" (Agnes et al., 2006). The rationale for that program was the observation, building on decades of opioid/CCK crosstalk research, that the C-terminal pharmacophores of opioid peptides (Tyr-Gly-Gly-Phe-... motifs from endogenous enkephalins) and of cholecystokinin (the C-terminal Trp-Met-Asp-Phe-NH₂ tetrapeptide that anchors CCK at its receptors) share enough structural features that a single short sequence might engage both receptor families. YGWDF is one of the short sequences explored in that series.
What it does
In the published assays the peptide was tested for its ability to bind the µ-opioid receptor (OPRM1) and the cholecystokinin A receptor (CCKAR / CCK-1R). The binding affinity recorded for this peptide in ChEMBL is Ki = 5700 nM. That number is in the micromolar range, which in receptor-binding terms is weak — orders of magnitude weaker than the endogenous ligands at either receptor. It is reported here for completeness as the measured value catalogued in ChEMBL (CHEMBL262172), not as evidence of meaningful pharmacological activity.
Evidence
- Human: No human studies. This is a research-stage chemistry ligand.
- Animal: No in vivo activity reported in the source paper specific to this short five-residue compound; the series was characterized primarily by in vitro receptor binding.
- In vitro: One reported binding measurement, Ki = 5700 nM, from the Agnes 2006 SAR series (ChEMBL CHEMBL262172).
Receptor context
The two named targets give the peptide its design intent:
- CCK-1R (CCKAR) is the gut-and-vagal cholecystokinin receptor. Endogenous CCK released from intestinal I-cells after a meal acts at CCK-1R on vagal afferents to produce the "I've eaten enough" satiety signal, and on the gallbladder and pancreas to drive bile release and digestive-enzyme secretion. The minimal active sequence of endogenous CCK at this receptor is the C-terminal sulfated octapeptide Asp-Tyr(SO₃)-Met-Gly-Trp-Met-Asp-Phe-NH₂; YGWDF overlaps with the C-terminal Trp-Met-Asp-Phe motif of CCK in spirit, but without the sulfated tyrosine that is essential for full CCK-1R potency (Agnes 2006, with the underlying CCK biology established by Mutt and Jorpes in 1968 and by Gibbs, Young, and Smith's 1973 satiety paper).
- µ-opioid receptor (OPRM1) is the principal receptor for morphine and for endogenous opioid peptides such as the enkephalins (Tyr-Gly-Gly-Phe-Leu/Met). The N-terminal Tyr of YGWDF is the canonical "message" residue of opioid peptide pharmacophores; the rationale of the Agnes 2006 series was to test whether short sequences could carry both the opioid Tyr-anchor and a CCK-like C-terminus.
The bifunctional design strategy itself — combining opioid agonism with CCK antagonism in one molecule — has been pursued in part because CCK is known to oppose opioid analgesia, so engaging both targets in one ligand was hoped to improve pain control. This specific peptide is best read as one data point in that exploration rather than a lead compound.
Known effects
There are no characterized in vivo effects attributable to this specific peptide. The only measured pharmacological property in the dossier is its weak receptor-binding affinity (Ki = 5700 nM, ChEMBL).
Regulatory status
Not a drug. Not approved by any regulator. Not a controlled substance. Not on the WADA Prohibited List under its ChEMBL identifier. This is a research-grade chemistry ligand from a 2006 medicinal-chemistry SAR series; it has no therapeutic, diagnostic, or wellness use.
Related peptides
- Cholecystokinin (CCK-8) — the endogenous octapeptide whose C-terminal Trp-Met-Asp-Phe-NH₂ motif inspired the C-terminal half of this peptide's design.
- Enkephalins (Met-enkephalin, Leu-enkephalin) — the endogenous opioid pentapeptides (Tyr-Gly-Gly-Phe-Met/Leu) whose Tyr-anchor pharmacophore inspired the N-terminal half.
- Other Agnes 2006 series members — additional bifunctional opioid/CCK ligands reported alongside this peptide in the same SAR study.
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 swapping just the middle amino acid in YGWDF shift the molecule from acting on the fullness receptor to acting mainly on the pain receptor?
If one residue controls the balance between two receptor targets, drug designers could create a precise toolkit of related peptides, each tuned to the right receptor ratio for a specific condition, from pure pain relief to appetite control to both.
Could activating the fullness receptor and the pain receptor simultaneously, with one molecule, prevent the weight gain that opioid painkillers often cause?
If this holds, people on long-term opioid therapy for chronic pain might maintain healthier body weight without an extra prescription, reducing a side effect that contributes to metabolic disease and medication discontinuation.
If the two ends of this peptide are chemically joined into a circle, would it last long enough in the body to act on both receptors?
Short peptides dissolve quickly in the bloodstream before reaching their targets. If a ring-shaped version of YGWDF survives long enough to reach pain and satiety receptors, it could become the starting point for an entirely new class of dual-action medicines for chronic pain and overeating.
Can YGWDF activate the fullness receptor in the gut directly, sending a stop-eating signal to the brain through nerves rather than through the bloodstream?
If the peptide works in the gut before entering the brain, it could reduce appetite and overeating without causing the drowsiness, dependence, or mood changes linked to opioid drugs, opening a safer path for treating obesity or compulsive overeating.
▸full evidence table1 metrics
| metric | value | tool |
|---|---|---|
| Ki | 5700 nM | GPCRDB/ChEMBL |
▸structural qualityopenfold3
| metric | value | note |
|---|---|---|
| gpde | 1.152 | 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{pep10311,
sequence = {YGWDF},
target = {cckar},
author = {peptidemodel},
year = {2026},
status = {bioassayed}
}