Dual pain-receptor research peptide (GFHRWDF)
A short lab-made peptide that latches onto two pain-related receptors at once (cholecystokinin and delta-opioid); 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
GFHRWDF is a short synthetic 7-residue peptide that came out of a medicinal-chemistry program designing molecules that bind more than one pain-relevant receptor at the same time. It is catalogued in ChEMBL as CHEMBL1172253 and is not a natural hormone, an approved drug, or a clinical compound — it is a research ligand. On the platform it sits as a probe that engages both the cholecystokinin-1 receptor (CCKAR) and the delta opioid receptor (OPRD1), with a reported binding affinity of Ki ≈ 18 nM.
History
The peptide was reported by Lee and colleagues (2010) in Bioorganic & Medicinal Chemistry Letters as part of a "design and synthesis of trivalent ligands targeting opioid, cholecystokinin, and melanocortin receptors for the treatment of pain" program. The motivation for that program — combining opioid, CCK, and melanocortin pharmacology in one scaffold — sits in the broader pain-pharmacology rationale that simultaneously engaging analgesia-promoting and anti-analgesia receptors might give cleaner pain control than a pure opioid agonist alone. This 7-mer is one of the building blocks from that paper.
What it does
In binding assays drawn from the Lee (2010) work, GFHRWDF interacts with the cholecystokinin-1 receptor and the delta opioid receptor with a Ki of about 18 nM. Beyond that bioassay number, there is no published characterisation of in-cell signalling, animal pharmacology, or human exposure for this specific sequence on the platform's reference set — it is a chemistry-stage ligand, not a tested drug.
Evidence
- Human: No human studies published for this sequence.
- Animal: No animal data on this specific 7-mer in the dossier.
- In vitro: Ki ≈ 18 nM at the receptor pair noted above, from the originating medicinal-chemistry paper (Lee 2010); ChEMBL ID CHEMBL1172253.
Regulatory status
Not an approved drug in any jurisdiction. Not on the WADA Prohibited List by name. This is a research-grade ligand reported in the medicinal-chemistry literature, with no clinical-stage development reported in the dossier.
Related peptides
Cholecystokinin (CCK) and its C-terminal octapeptide CCK-8 are the endogenous ligands at the cholecystokinin-1 receptor that this molecule was designed to engage; dynorphin and enkephalin family peptides are the endogenous ligands at the delta opioid receptor. This card's sequence (GFHRWDF) is unrelated to the canonical CCK C-terminal motif (DYMGWMDF-NH₂) — it is a designed ligand, not a CCK fragment.
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.
Do two oppositely charged amino acids inside GFHRWDF snap together to lock the peptide into the right shape for binding, even before it reaches a receptor?
If the peptide self-organises its shape, chemists could lock that shape permanently with a simple molecular staple, potentially producing a more potent and longer-lasting compound from the same basic scaffold.
Could the same peptide designed to fight pain also reduce appetite by activating a gut signal that tells the brain the stomach is full?
If appetite suppression kicks in at lower doses than pain relief, people with both chronic pain and obesity might one day manage both conditions with a single carefully dosed compound, reducing the pill burden and potential side effects of combination therapy.
Does the unusual starting amino acid in GFHRWDF naturally steer it away from the receptor most responsible for opioid addiction and fatal overdose?
If GFHRWDF truly avoids the mu-opioid receptor, it could serve as a template for pain medicines that are far less likely to cause dependence or life-threatening respiratory depression, a major unmet need in pain management.
Would swapping one hydrogen for a fluorine atom on the second building block of GFHRWDF make it bind the opioid receptor more tightly while leaving the other receptor interaction intact?
If a one-atom change boosts precision at the opioid receptor, it would confirm a simple chemical rule for improving this whole class of dual-target peptides, potentially cutting years off the optimisation timeline for a safer painkiller.
▸full evidence table1 metrics
| metric | value | tool |
|---|---|---|
| Ki | 18 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{pep10307,
sequence = {GFHRWDF},
target = {cckar},
author = {peptidemodel},
year = {2026},
status = {bioassayed}
}