Gila monster venom peptide that activates the GLP-1 diabetes target (Exendin-3)
A natural peptide from Gila monster venom that activates the same receptor targeted by diabetes drugs like semaglutide; 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.
Snapshot
Class: Venom-derived glucagon superfamily peptide
Evidence tier: In vitro / assay evidence
Status: No approved therapeutic status identified. Research and reference compound; not an approved drug.
Best-supported effect: Receptor-mediated cAMP stimulation in pancreatic acinar cells (in vitro, low-concentration exendin-receptor interaction) and VIP-receptor-mediated cAMP and amylase release at higher concentrations — characterized in original isolation studies.
Main caveat: No animal efficacy data or human trial data are present. All described activity is from biochemical receptor and cell-system characterization.
What this is
Exendin-3 is a 39-amino-acid peptide originally isolated from the venom of the beaded lizard (Heloderma horridum). It is a member of the glucagon superfamily, a family of structurally related peptides that includes glucagon, GLP-1, VIP, and related hormones. Exendin-3 is distinct from exendin-4 (isolated from Heloderma suspectum), which served as the structural basis for the approved GLP-1 receptor agonist exenatide; the two exendins are related but separate molecules with different sequences. Published research characterizes exendin-3 as interacting with putative exendin receptors at low concentrations and with VIP receptors at higher concentrations, producing cAMP and amylase responses in pancreatic acinar cell systems. Exendin-3 has no approved therapeutic application.
Evidence map
| Evidence layer | Grade | What it supports |
|---|---|---|
| Human | None identified | No human evidence is identifieds available literature |
| Animal | None identified | No animal experiment data are identifieds available literature |
| In vitro | Weak | Receptor-mediated cAMP stimulation in pancreatic acinar cell systems; VIP-receptor-mediated cAMP and amylase release at higher concentrations; characterized in the original 1992 isolation paper |
| Computational | None identified | No structure prediction or docking data are identifieds available literature |
| Mechanism | Plausible | Dual-receptor interaction model described in source: exendin-receptor at low concentrations, VIP receptor at higher concentrations; mechanistic basis consistent with glucagon superfamily pharmacology |
Claim check
| Claim | Verdict | Evidence layer | Confidence |
|---|---|---|---|
| Stimulates cAMP in pancreatic acinar cells via exendin receptors | Supported (in vitro) | In vitro | Medium — original isolation characterization; single available literature |
| Stimulates cAMP and amylase release via VIP receptors at higher concentrations | Supported (in vitro) | In vitro | Medium — described in original isolation source; single available literature |
| Therapeutic equivalence to exenatide or exendin-4 | Not established | None | High confidence in absence — exendin-3 is a distinct molecule; evidence from exendin-4-derived compounds cannot be applied to this card |
| Any human efficacy for any indication | Not established | None | High confidence in absence — no human trial data present in available literature |
Assay conditions
This section reports concentrations or conditions used in assays. It does not establish animal or human exposure.
| Context | System | Assay condition | Timepoint | Endpoint | Limitation |
|---|---|---|---|---|---|
| Receptor interaction characterization | Pancreatic acinar cell system | Low concentration (exendin-receptor range) | Not individually extracted from source | Increase in cellular cAMP | Source descriptor only; exact concentrations not individually extracted |
| Receptor interaction characterization | Pancreatic acinar cell system | Higher concentration (VIP-receptor range) | Not individually extracted from source | Increase in cellular cAMP and amylase release | Source descriptor only; exact concentrations not individually extracted |
Assay limitations
- Assay conditions (cell system, concentration ranges, species of origin for cell preparations) are not individually extracted from the available literature.
- receptor activity in summary terms only; no tabular assay results, MIC values, or dose-response curves are reproduced in the available literature file.
- In vitro receptor interactions do not establish in vivo pharmacology, systemic tolerability, or therapeutic effect in any species.
- No comparison to exendin-4 or GLP-1 receptor agonist potency is documented.
Mechanism
Exendin-3 is described in the available literature as acting through two receptor systems in a concentration-dependent manner: at low concentrations it interacts with putative exendin receptors on pancreatic acinar cells, producing an increase in intracellular cAMP; at higher concentrations it interacts with vasoactive intestinal peptide (VIP) receptors, stimulating both cAMP accumulation and amylase release. This dual-receptor pharmacology is consistent with the structural relationship of exendin-3 to the glucagon superfamily, members of which share receptor cross-reactivity at sufficient concentrations. The specific identity and classification of the "putative exendin receptor" described in the 1992 isolation paper reflects the nomenclature and receptor landscape of that period; subsequent work in the exendin field has more precisely characterized GLP-1 receptor interactions for related peptides, but the available literature does not individually document exendin-3's GLP-1 receptor affinity or selectivity data.
Chemistry
| Field | Value |
|---|---|
| Sequence (one-letter) | HSDGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPS |
| Sequence (three-letter) | H-His-Ser-Asp-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH₂ |
| Length | 39 amino acids |
| Topology | Linear |
| C-terminal modification | Amide (–NH₂) |
| Origin | Venom of Heloderma horridum (beaded lizard) |
| Molecular weight | Not provided in source |
| Formula | Not provided in source |
| CAS | Not provided in source |
| Sequence confidence | Needs review |
Open questions
- Animal and in vivo pharmacology: No animal experiment data are present. Whether the in vitro receptor activity translates to in vivo effects in any species is not established from the available literature.
- GLP-1 receptor affinity: Exendin-3's affinity and selectivity for the GLP-1 receptor relative to other glucagon superfamily receptors is not documented in the available literature. The 1992 isolation paper predates precise GLP-1 receptor pharmacology; updated binding data are not individually extracted here.
- Comparison to exendin-4: The sequence and pharmacological differences between exendin-3 and exendin-4 (the basis for exenatide) are not analyzed in the available literature. Whether exendin-3 shares exendin-4's GLP-1 receptor agonist properties is not established in this card.
- Human relevance: No human trial, pilot, or clinical characterization is present.
- Sequence verification: Sequence is drawn from the CU source entry only. Independent primary-source verification against the Eng 1992 original publication has not been performed in this card-writing pass.
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.9116411805152893 | boltz-2 |
| ranking score | 0.7716017961502075 | boltz-2 |
▸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 | colabfold_nvidia |
| diffusion samples | 1 |
| runtime | — |
| predicted by | mlx@peptide |
| predicted at | 2026-04-25 |
▸citationbibtex
@peptide{pep10589,
sequence = {HSDGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPS},
target = {glp-1r},
author = {peptidemodel},
year = {2026},
status = {synthesized}
}