Gut-fullness receptor research peptide (YFHRWDF)
A synthetic 7-amino-acid compound that latches onto the receptor the gut hormone CCK uses to signal fullness and trigger digestion; 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 seven-amino-acid synthetic peptide (sequence YFHRWDF) designed as a ligand for the CCK-1 receptor (CCKAR), the gut-and-brain receptor through which the natural hormone cholecystokinin signals satiety, gallbladder contraction, and pancreatic enzyme release. It is not a hormone people take — it is a research compound, catalogued in ChEMBL as CHEMBL1172429, that came out of a medicinal-chemistry program at the University of Arizona exploring multi-target ligands for pain (Lee et al., 2010). In binding assays at CCKAR, it shows an IC50 of 1.585 nM, placing it in the low-nanomolar range typical of well-engineered receptor ligands.
History
The peptide was reported as part of a 2010 paper by Lee and colleagues in Bioorganic & Medicinal Chemistry Letters titled "Design and synthesis of trivalent ligands targeting opioid, cholecystokinin, and melanocortin receptors for the treatment of pain." The work belongs to a long-running effort at Victor Hruby's Arizona group to build single molecules that engage several receptors implicated in pain processing simultaneously, on the rationale that opioid analgesia paired with concurrent activity at non-opioid pain pathways (including CCK, which functions in part as an anti-opioid system) might separate analgesia from opioid tolerance and tachyphylaxis. The YFHRWDF 7-mer is one component within that trivalent design — the fragment intended to address the CCK arm.
What it does
In a cell-free competitive binding assay against CCKAR, the peptide displaces a reference radioligand with an IC50 of 1.585 nM (CHEMBL1172429). That number tells you it binds the receptor tightly; it does not tell you whether it activates the receptor, blocks it, or biases downstream signaling — those functional questions are not resolved by a binding IC50 alone and are not addressed in the dossier for this entry. CCKAR itself is the Gq-coupled receptor that natural CCK uses to drive meal-ending satiety via vagal afferents, gallbladder smooth-muscle contraction, and pancreatic acinar enzyme secretion; any compound binding CCKAR with low-nanomolar affinity is a candidate tool for probing those pathways, but the published context for this specific peptide is pain pharmacology, not metabolic or digestive physiology.
Evidence
- Human: No human studies. This is a preclinical research compound.
- Animal: Not reported in the dossier for this specific 7-mer fragment.
- In vitro: One reported measurement — CCKAR binding IC50 = 1.585 nM (ChEMBL CHEMBL1172429, from Lee et al. 2010).
Related peptides
The peptide's parent context is endogenous cholecystokinin (CCK) and its receptor-active C-terminal octapeptide CCK-8, both of which act at CCKAR. The Lee 2010 trivalent-ligand program also included opioid- and melanocortin-receptor-targeted fragments designed to be linked into a single multi-target molecule.
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 this small peptide latch onto the satiety receptor at a different spot than the body's own fullness signal?
If true, it could lead to appetite-suppressing drugs that trigger the 'full' signal without also squeezing the gallbladder or flooding the gut with digestive enzymes, making them safer and better tolerated.
Do two specific amino acids in the middle of this peptide substitute for the chemically delicate sulfate that the body's own hormone needs to work?
If true, chemists could design stable, easy-to-manufacture CCK-based drugs that do not degrade in blood the way the natural hormone does, opening the door to oral or long-acting therapies.
Can this peptide prevent the body's own 'anti-opioid' signal from weakening painkiller effects over time?
If it works, patients on opioids for chronic pain might stay on lower doses for longer, reducing the risk of dose escalation and dependence.
Can this peptide trigger the 'I'm full' signal in the gut without causing the anxiety or panic that brain CCK receptors can produce?
A gut-selective CCK drug would be much safer for long-term use in obesity or post-meal pain, since it would control appetite or digestion without affecting mood or triggering panic attacks.
Do the three ring-shaped amino acids in this peptide force it into a stable shape that fits the receptor like a key and resists digestion?
Peptide drugs are often broken down too quickly in the body to be useful. If this natural rigidity can be reinforced with small chemical tweaks, it could become a stable, manufacturable drug candidate rather than just a lab tool.
Could this peptide reduce the intense gallbladder squeezing that causes post-meal pain in some patients?
Millions of people suffer from painful gallbladder spasms without a good drug option. If this peptide can gently blunt those contractions, it could spare patients from unnecessary gallbladder removal surgery.
▸full evidence table1 metrics
| metric | value | tool |
|---|---|---|
| IC50 | 1.585 nM | GPCRDB/ChEMBL |
▸structural qualityopenfold3
| metric | value | note |
|---|---|---|
| gpde | 0.984 | 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{pep10308,
sequence = {YFHRWDF},
target = {cckar},
author = {peptidemodel},
year = {2026},
status = {bioassayed}
}