Secretin-receptor activator (CHEMBL1256314)
A lab-made copy of secretin, the gut hormone that helps control digestion, tuned to switch on its receptor, 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
This is a 27-amino-acid research peptide designed to act at the secretin receptor (SCTR), the same receptor that the hormone secretin uses to signal through the gut. It is a constrained analog of secretin's active core: the two cysteines visible at positions 7 and 9 of the stored sequence (HSDGTFCSCYSRLQDSARLQRLLQGLV) form an intramolecular disulfide bond that locks the N-terminus into the shape it adopts when bound to its receptor (Dong et al., 2010). The disulfide ring is not represented in the raw 1-letter sequence shown — only the two cysteines that close it. It is catalogued in ChEMBL as CHEMBL1256314 and is a tool compound, not an approved drug.
History
The peptide comes out of a structure-activity line of work on secretin analogs aimed at understanding which conformation of secretin's amino terminus is the one that actually engages the receptor. Dong and colleagues (2010) used intramolecular disulfide bond constraints — replacing pairs of residues with cysteines that then form a covalent bridge — to lock the amino terminus into candidate shapes and test which shapes preserved binding and signaling. The work was published in Bioorganic & Medicinal Chemistry Letters.
What it does
In a cellular assay, it activates the human secretin receptor with an EC50 of 0.1 nM (ChEMBL CHEMBL1256314). That puts it in the same potency range as native secretin at its own receptor. The point of the molecule is not therapeutic — it is to test a structural hypothesis about how the flexible N-terminus of secretin docks into its receptor.
Mechanism
Native secretin engages the secretin receptor, a class B G-protein-coupled receptor, in two parts: the C-terminal helix of the peptide first anchors to the receptor's extracellular domain, and then the flexible N-terminus inserts into the transmembrane core to trigger signaling. The conformation that the N-terminus must adopt at this second step has been the central question for the field. Dong and colleagues (2010) used the cysteine-to-cysteine disulfide approach to physically constrain candidate conformations of the N-terminus and read out which constraints preserved binding and activation. The Cys7–Cys9 disulfide bridge in this 27-mer is one such constraint, and its sub-nanomolar EC50 supports the hypothesis that the active-state N-terminus is compatible with that local geometry.
Evidence
- Human: No human trials. This is a research tool compound.
- In vitro: EC50 = 0.1 nM at the human secretin receptor (ChEMBL CHEMBL1256314). The disulfide-constraint design and structure-activity rationale are described in Dong et al. (2010).
- Animal: No animal studies in the dossier.
Regulatory status
- US/EU: Not approved. Research-use chemical; not a drug product.
- WADA: Not specifically listed.
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 peptide bind so tightly mainly because its shape is already fixed before it reaches its receptor?
If this turns out to be the reason, drug designers could try to build next-generation gut-hormone drugs that work at very low doses by copying the locked shape, which might help reduce side effects. That could matter for patients needing long-term therapy for conditions such as chronic pancreatitis or short bowel syndrome.
If the chemical ring that gives this peptide its shape were made from tougher chemistry, could it survive long enough in the body to be a drug?
If the peptide could survive longer in the bloodstream, it might become a real treatment for digestive disorders or other conditions where the secretin pathway is disrupted, helping patients who currently have no good options.
Does locking the front end of this peptide into a ring stop it from triggering related receptors that share similar chemistry?
If this peptide avoids related receptors, it could be developed into a safer research tool or drug for conditions like pancreatitis without causing unwanted blood pressure or airway effects linked to related receptors.
Could this strong secretin-receptor activator change how bone is broken down, which is relevant to osteoporosis?
The secretin receptor does appear in bone cells, so if this peptide changes how bone is broken down, it could point scientists toward a new line of osteoporosis research. This is an early, unproven idea rather than a near-term treatment.
Do the rigid front end and the helical tail of this peptide each latch onto a different part of the receptor?
If each end binds a separate site, researchers could try making shorter versions that block or only partly activate the receptor, which might be useful where full receptor activation is unwanted.
▸full evidence table1 metrics
| metric | value | tool |
|---|---|---|
| EC50 | 0.1 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{pep10445,
sequence = {HSDGTFCSCYSRLQDSARLQRLLQGLV},
target = {sctr},
author = {peptidemodel},
year = {2026},
status = {bioassayed}
}