Tiny research peptide (CHEMBL1172246)
A four-letter lab-made peptide that hits three different body receptors at once; 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
CCKAR ligand CHEMBL1172246 is a short four-amino-acid peptide (sequence YGHR) reported in a 2010 medicinal-chemistry paper that set out to make a single molecule capable of engaging three different receptors implicated in pain: the delta opioid receptor (DOR/OPRD1), the cholecystokinin A receptor (CCKAR), and the melanocortin 4 receptor (MC4R). It is not an approved drug, not a clinical candidate, and not a peptide sold for wellness use — it is a research compound catalogued in ChEMBL under the identifier CHEMBL1172246, with a measured binding affinity of IC50 = 125.89 nM reported by the authors. The motivation behind it is the long-standing idea that combining activity at the opioid system with modulation of co-regulating receptors (CCK and melanocortin signaling) could in principle produce analgesia with a different side-effect profile than a pure opioid.
History
The peptide was described by Lee and colleagues (2010) in Bioorganic & Medicinal Chemistry Letters, in a paper titled "Design and synthesis of trivalent ligands targeting opioid, cholecystokinin, and melanocortin receptors for the treatment of pain." The work belongs to a multivalent-ligand design tradition in pain pharmacology in which short peptide fragments or small-molecule pharmacophores known to engage individual receptors are linked or combined to produce a single chemical entity addressing multiple targets at once. The CCK and melanocortin systems were chosen as co-targets because of pre-existing evidence that activation of CCK and central melanocortin signaling each contribute to opioid tolerance and to the maintenance of certain chronic pain states, so an opioid agonist combined with antagonism or modulation of these pathways might preserve analgesia while limiting the development of tolerance.
What it does
In the assay reported by Lee and colleagues, the compound binds the cholecystokinin A receptor (CCKAR) with an IC50 of 125.89 nM. The paper describes it as a trivalent ligand designed against the delta opioid receptor, CCKAR, and MC4R simultaneously, so binding at the other two targets is part of the intended pharmacology. Beyond receptor binding in vitro, no clinical or in vivo efficacy data are attached to this specific four-mer on the platform.
Evidence
- Human: No human studies. This is a research compound with no clinical development.
- Animal: Not characterized in the dossier sources available for this card.
- In vitro: Binding to CCKAR with IC50 = 125.89 nM, reported by Lee and colleagues (2010) and catalogued in ChEMBL as CHEMBL1172246.
Related peptides
The endogenous ligand for the cholecystokinin A receptor is cholecystokinin itself, the gut-and-brain peptide hormone whose C-terminal octapeptide (CCK-8) is the minimal active sequence at CCK-1R and whose biology — postprandial satiety, gallbladder contraction, pancreatic secretion — provides the physiologic context for any CCKAR-targeted ligand. The endogenous ligand at MC4R, the melanocortin-4 receptor co-target of this compound, is α-MSH; MC4R is the same receptor engaged by the clinical melanocortin agonists setmelanotide and bremelanotide. The opioid co-target OPRD1 (delta opioid receptor) is the target of compounds in the enkephalin and dermorphin/deltorphin families.
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 YGHR actually engage all three targeted receptors equally, or is one receptor doing most of the work?
If the compound's activity is dominated by a single receptor, researchers could focus development efforts more precisely, avoiding wasted effort and designing better versions that either improve true multi-receptor engagement or optimize for the one receptor that actually responds.
Does replacing the flexible glycine in YGHR destroy its ability to bind some receptors while preserving others?
If true, this discovery would provide a simple chemical rule for tuning which pain receptors a drug hits, allowing medicinal chemists to dial in desired receptor combinations with a single amino acid substitution, making drug design faster and more predictable.
Would a circular version of YGHR survive in the bloodstream long enough to be a useful drug, and would it become more selective in the process?
If true, this would convert a promising but fragile research molecule into a more drug-like compound, bringing an entirely new class of multi-target pain peptides one step closer to real-world clinical use.
Could this molecule, designed as a painkiller, also act on the gut receptor that stops hunger?
If true, people with both chronic pain and obesity could potentially benefit from a single treatment, addressing two conditions that often worsen each other, without requiring the CNS-active drugs that carry addiction or mood risks.
▸full evidence table1 metrics
| metric | value | tool |
|---|---|---|
| IC50 | 125.89 nM | GPCRDB/ChEMBL |
▸structural qualityopenfold3
| metric | value | note |
|---|---|---|
| gpde | 1.318 | 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{pep10305,
sequence = {YGHR},
target = {cckar},
author = {peptidemodel},
year = {2026},
status = {bioassayed}
}