Kisspeptin-2: fish reproductive-signaling peptide (FNFNPFGLRF)
A natural fish hormone that triggers the release of reproductive hormones in fish; not found in humans and 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: Endogenous fish neuropeptide / reproductive signaling decapeptide
Evidence tier: Animal-only evidence
Status: No approved therapeutic status identified. Research peptide studied in teleost fish models.
Best-supported effect: Stimulation of luteinizing hormone and follicle-stimulating hormone secretion in teleost fish (animal models); greater potency than Kisspeptin-1 in this system
Main caveat: The KiSS-2 gene is absent in placental mammals, including humans. No mammalian or human biology is established for this peptide.
What this is
Kisspeptin-2 is a ten-amino-acid peptide (decapeptide) encoded by the KiSS-2 gene, one of two paralogous kisspeptin genes identified in non-placental vertebrates. It is an endogenous peptide in teleost fish species such as sea bass, where KiSS-2 mRNA is expressed in brain and gonadal tissue. The KiSS-2 gene appears to have been lost in the lineage leading to placental mammals, and Kisspeptin-2 has no established endogenous counterpart in humans. Functional studies in fish indicate that Kisspeptin-2 is more potent than its paralog Kisspeptin-1 in stimulating gonadotropin release, making it a subject of comparative reproductive endocrinology research in non-mammalian vertebrate species.
Evidence map
| Evidence layer | Grade | What it supports |
|---|---|---|
| Human | None | No human evidence is present. The KiSS-2 gene is absent in placental mammals. |
| Animal | Weak | Gonadotropin (LH and FSH) secretion stimulated by Kisspeptin-2 in teleost fish (sea bass); comparative potency advantage over Kisspeptin-1 reported in the same fish system |
| In vitro | None | No cell or binding assay data are present |
| Computational | None | No computational or structural prediction data are present |
| Mechanism | Plausible | Kisspeptin-2 is proposed to act through kisspeptin receptor (Kiss1R / GPR54) in fish; receptor specificity relative to mammalian Kiss1R is not established in the available literature |
Animal evidence is based on a single published comparative study in sea bass; independent replication in additional species or systems is not documented.
Claim check
| Claim | Verdict | Evidence layer | Confidence |
|---|---|---|---|
| Stimulates LH and FSH secretion in teleost fish | Supported (animal) | Animal | Medium — single study; species-limited to teleost fish |
| Greater gonadotropin-releasing potency than Kisspeptin-1 | Supported (animal) | Animal | Medium — comparative finding within single fish study; not replicated in other systems per source |
| Relevant to human reproductive biology | Not established | None | High — the KiSS-2 gene is absent in placental mammals; no human biology basis identified in source |
| Suitable as a therapeutic candidate in mammals | Not established | None | High — no mammalian experimental data present in source; gene-loss biology creates a fundamental translation barrier |
Experimental exposure
This section reports exposure used in animal experiments. It does not establish human dosing.
| Context | System | Experimental exposure | Duration | Endpoint | Limitation |
|---|---|---|---|---|---|
| Comparative fish study | Sea bass (Dicentrarchus labrax) | Kisspeptin-2 decapeptide; exact dose and route not individually extracted from source | Not reported in source | LH and FSH secretion; comparative potency vs. Kisspeptin-1 | Single species; no mammalian translation established; exposure details not individually extracted |
Preclinical safety signals
No toxicology or safety data are present. The peptide has been studied only in teleost fish comparative experiments. No mammalian safety or tolerability data are identified.
Regulatory status
No approved therapeutic status identified. This card describes a research peptide derived from comparative vertebrate genomics and fish reproductive biology, not an approved medicine. No WADA classification data are present.
| Region / body | Status | Notes |
|---|---|---|
| US (FDA) | No approved status identified | Not an approved drug; no IND or clinical program identified in source |
| EU (EMA) | No approved status identified | Not an approved medicine; source does not report EU regulatory history |
| WADA | Not checked | Source does not report anti-doping classification; status not independently verified in this card |
Mechanism
Kisspeptin-2 is proposed to act as an agonist at kisspeptin receptors in teleost fish, stimulating the hypothalamic–pituitary–gonadal axis and triggering the release of luteinizing hormone and follicle-stimulating hormone. In the available literature, comparative functional experiments in sea bass demonstrate greater gonadotropin-stimulating activity for Kisspeptin-2 than for Kisspeptin-1, consistent with differential receptor binding or activation potency.
The mammalian kisspeptin system is mediated by Kiss1R (GPR54), encoded by the KiSS-1 gene lineage. Because the KiSS-2 gene has been lost in placental mammals, there is no established endogenous target for exogenous Kisspeptin-2 in humans. Whether Kisspeptin-2 could cross-activate mammalian Kiss1R is not addressed in the available literature.
Target confidence: Inferred from fish comparative studies; not verified in mammalian systems.
Chemistry
| Field | Value |
|---|---|
| Sequence (single-letter) | FNFNPFGLRF |
| Full notation | H-Phe-Asn-Phe-Asn-Pro-Phe-Gly-Leu-Arg-Phe-OH |
| Length | 10 amino acids |
| Topology | Linear |
| Modifications | None reported; free N-terminus (H-), free C-terminus (-OH) |
| Molecular weight | Not reported in source |
| Formula | Not reported in source |
| CAS | Not reported in source |
| Sequence confidence | Needs review — single source (catalog/database entry); no independent sequence verification in available literature |
Open questions
- Mammalian receptor cross-reactivity: Whether Kisspeptin-2 binds or activates the mammalian kisspeptin receptor (Kiss1R / GPR54) has not been established in the available literature. This is a fundamental prerequisite before any mammalian relevance can be assessed.
- Gene-loss implications: The KiSS-2 gene is absent in placental mammals. Whether any functional analog exists or whether the peptide could have pharmacological activity in mammalian systems via cross-receptor binding remains unstudied per the available literature.
- Species generalizability: Animal evidence is limited to sea bass in the available literature. Whether the gonadotropin-stimulating effect generalizes to other non-placental vertebrates or to any mammalian species is not established.
- Quantitative exposure data: the available literature does not individually extract dose, route, or timing for the fish experiments. These parameters are absent from this card.
- In vitro characterization: No receptor binding assays, cell-based assays, or biochemical characterization data are identified. Receptor affinity and selectivity are unknown from available literature.
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.
Could this naturally fish-specific peptide help control breeding in farmed fish while posing less risk to wild mammals if it leaks into rivers?
Fish farmers use hormone treatments to synchronize breeding, but these chemicals can affect wildlife in nearby waterways. A peptide that only works in fish could make aquaculture more environmentally responsible, benefiting both the industry and ecosystems downstream of fish farms.
Could this fish peptide stimulate the human fertility receptor through a different route than the body's own kisspeptin, avoiding the receptor burnout that limits current treatments?
Treatments that avoid receptor burnout could work over longer periods without losing effectiveness. This would matter greatly for people receiving kisspeptin-based therapies for infertility, potentially reducing the need for complicated dosing regimens.
If scientists close this fish peptide into a ring, could it survive long enough in the bloodstream to work as a once-daily fertility drug?
Current kisspeptin-based treatments break down quickly and need frequent injections. A ring-shaped version could last much longer in the body, potentially allowing simpler dosing for people being treated for infertility or hormone disorders.
Does this fish peptide stick specifically to the fertility receptor without also hitting the nearby receptors that control pain and appetite?
If kisspeptin-2 is naturally selective, it would be a cleaner starting point for drugs than other RF-amide peptides that hit multiple receptors. Patients could benefit from fertility treatments with fewer unintended side effects.
Does a kink in the middle of this fish peptide force its active end into the right shape to hit its receptor harder than the related peptide?
If confirmed, drug designers could lock this bend in place artificially, creating a more stable, potent molecule that activates fertility-related receptors more efficiently. This could lead to smaller, cheaper reproductive hormone treatments.
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.9193800687789917 | boltz-2 |
| ranking score | 0.7435304522514343 | boltz-2 |
▸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{pep10541,
sequence = {FNFNPFGLRF},
target = {kiss1r},
author = {peptidemodel},
year = {2026},
status = {synthesized}
}