Kisspeptin-54: natural hormone that triggers puberty and fertility signaling
A natural brain hormone that tells the body to start and maintain puberty and reproductive cycles; studied as a potential fertility treatment but not yet an approved drug.
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
Aliases: Metastin (human)
Class: Endogenous neuropeptide / KISS1R ligand
Evidence tier: In vitro / assay evidence
Status: No approved therapeutic status identified in attached sources
Best-supported effect: High-affinity binding to kisspeptin receptor (KISS1R / GPR54) in receptor-binding assays (Ki ~1.45 nM at human GPR54, ~1.81 nM at rat GPR54)
Main caveat: Receptor-binding data do not establish in vivo efficacy; no animal efficacy data or human trial data are identified
What this is
Kisspeptin-54 (KP54) is the full-length, 54-amino-acid human form of kisspeptin, an endogenous peptide encoded by the KISS1 gene. It is also known under the historical alias Metastin, which reflects its initial identification as a product of a metastasis-suppressor gene locus. KP54 is the endogenous ligand for the G-protein-coupled receptor KISS1R (GPR54), a receptor involved in reproductive neuroendocrine regulation and, based on the gene's original characterization, in the suppression of tumor metastasis. The 54-residue sequence includes the conserved C-terminal RF-amide motif shared with shorter kisspeptin fragments (KP10, KP13, KP14), which are considered the minimally active receptor-binding region.
Evidence map
| Evidence layer | Grade | What it supports |
|---|---|---|
| Human | None identified | No human trial data identifieds available literature |
| Animal | None identified | Referenced animal study (mouse gonadotropin; Gottsch 2004) listed in source but animal efficacy data not individually extracted |
| In vitro | In vitro moderate | Receptor-binding assay data: Ki 1.81 nM (rat GPR54) and 1.45 nM (human GPR54); source also describes KISS1-encoding-gene role in tumor-metastasis suppression and gonadotropin stimulation |
| Computational | None identified | No computational or structural prediction data attached |
| Mechanism | Plausible | Agonism at KISS1R (GPR54) is the stated primary mechanism; downstream gonadotropin-releasing hormone (GnRH) pathway engagement is biologically plausible based on the receptor class |
Claim check
| Claim | Verdict | Evidence layer | Confidence |
|---|---|---|---|
| Binds KISS1R (GPR54) with high affinity | Supported (in vitro) | In vitro | Medium — Ki values from single vendor-source catalog entry; independent replication not extracted |
| Stimulates gonadotropin secretion | Supported (in vitro / early animal) | In vitro | Low — stated as catalog descriptor with supporting reference (mouse model, Gottsch 2004); detailed study data not individually extracted |
| Suppresses tumor metastasis | Weak (in vitro / descriptor) | In vitro | Low — stated as catalog descriptor based on the KISS1 gene's metastasis-suppressor characterization (Kotani 2001); no in vivo anti-metastatic trial data attached |
| Human therapeutic use for any indication | Not established | None | High — no human trial data present |
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-binding assay | Rat GPR54 receptor | Concentration yielding Ki = 1.81 nM | Not individually extracted | Receptor binding affinity (Ki) | Single catalog-available data point; assay protocol not fully described in source |
| Receptor-binding assay | Human GPR54 receptor | Concentration yielding Ki = 1.45 nM | Not individually extracted | Receptor binding affinity (Ki) | Single catalog-available data point; assay protocol not fully described in source |
Assay limitations
- Binding Ki values are reported as catalog descriptor data; the original assay methodology, conditions, and controls are not individually extracted's available literature.
- Receptor binding affinity does not establish functional agonism, downstream signaling magnitude, or in vivo activity.
- No animal efficacy data or human safety or efficacy data are identified.
- In vitro binding data cannot be extrapolated to systemic pharmacokinetics, bioavailability, or therapeutic outcome in any species.
Regulatory status
No approved therapeutic status identified. This card describes a research-grade peptide based on an endogenous human sequence. No FDA, EMA, or equivalent major regulatory approval for any therapeutic use is described in the attached sources.
| Region / body | Status | Notes |
|---|---|---|
| US (FDA) | No approved therapeutic use identified | Not an approved drug; research-grade synthetic peptide |
| EU (EMA) | No approved therapeutic use identified | Status not extracted in source |
| WADA | Not checked in this card | Source-bundle does not address anti-doping classification |
Mechanism
KP54 is an agonist at KISS1R (GPR54), a Gq/11-coupled G-protein-coupled receptor. Receptor activation engages phospholipase C–mediated signaling, increasing intracellular calcium. In the hypothalamic reproductive axis, KISS1R activation on GnRH neurons is recognized as a key upstream regulator of GnRH pulse generation and gonadotropin (LH, FSH) release. The connection to tumor-metastasis suppression reflects the original KISS1 gene characterization: the gene product was identified as a suppressor of metastatic colonization, independent of primary tumor growth. The specific mechanism by which KP54 or its fragments inhibit metastatic signaling is not fully described in the attached source.
The receptor target (KISS1R / GPR54) is stated consistently in available literature. Binding data (Ki values) are from in vitro assay; downstream functional activity in human tissue is not characterized in the attached source.
Chemistry
| Field | Value |
|---|---|
| Sequence (one-letter) | GTSLSPPPESSGSRQQPGLSAPHSRQIPAPQGAVLVQREKDLPNYNWNSFGLRF-NH2 |
| Length | 54 amino acids |
| C-terminal modification | C-terminal amidation (-NH2) |
| Topology | Linear |
| N-terminus | Free (H-) |
| Molecular weight | Not provided in source |
| Formula | Not provided in source |
| CAS | Not provided in source |
| Sequence confidence | Needs review — single vendor-source; not cross-checked against an independent primary sequence database in this card |
The sequence contains the conserved C-terminal RF-amide motif (…SFGLRF-NH2), shared with the shorter kisspeptin fragments (KP10, KP13, KP14) and considered the minimally active KISS1R-binding region.
Open questions
- In vivo efficacy — reproductive axis: Does exogenous administration of KP54 produce a reproducible, dose-dependent gonadotropin response in human subjects? Animal and clinical data for shorter kisspeptin fragments exist in the broader literature but are not extracted's available literature.
- Anti-metastatic mechanism: What specific receptor pathway mediates KISS1-associated metastasis suppression? the gene's metastasis-suppressor role but does not detail the molecular mechanism attached to KP54 specifically.
- Fragment vs full-length activity: Shorter kisspeptin fragments (KP10) are widely studied for KISS1R agonism; whether KP54 confers distinct pharmacological properties relative to KP10 in vivo is not addressed in the attached source.
- Human safety profile: No toxicology, pharmacokinetics, or adverse-event data for exogenous KP54 administration are identified.
- Formulation and stability: lyophilized storage at ≤ −20 °C; in vivo formulation, stability, and route-specific pharmacokinetics are not addressed.
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 the extra, probably unstructured section of KP54 change how strongly and how long it activates its receptor compared to shorter kisspeptin fragments?
If true, doctors could pick a longer-acting or shorter-acting kisspeptin form for fertility treatment, better matching natural hormone pulses. The idea is reasonable but not yet shown: real differences between KP54 and the shorter KP10 are reported in animals, while the specific structure numbers behind this proposal are not in this card.
Could acting on the kisspeptin receptor, which is overactive in papillary thyroid cancer, slow tumor growth?
The receptor really is overexpressed and does fire off a growth signal in these tumor cells. But whether switching it on slows growth or speeds it up is still unknown, so it is not yet clear whether a KP54-like activator or a blocker would help. Resolving this could open a targeted option beyond surgery and radioiodine.
Can KP54 help stop cancer cells from spreading even in tumors that lack the kisspeptin receptor?
Some studies do show the KISS1 gene suppresses spread in cells that lack its receptor, so a receptor-free route is plausible. The specific idea here, that KP54's proline-rich region grips the surrounding tissue scaffold, is one untested guess among several. If a receptor-free route exists, it could widen which cancers might benefit.
Could engineers build a better version by replacing the part of KP54 that breaks down quickly with something that survives longer in the bloodstream?
A longer-lasting kisspeptin could mean fewer injections during fertility treatment. One caution: in animals the full-length KP54 already lasts longer than the short fragment, so the tail may matter for that staying power. Whether an engineered version truly beats native KP54 would have to be tested, not assumed.
Does KP54 send a somewhat different internal signal than KP10, even though both bind the same receptor?
If the two forms favor different internal pathways, clinicians could pick the form that avoids receptor burnout during fertility treatment. This is a reasonable but unproven idea: reported KP54-versus-KP10 differences exist, yet some studies show KP54 still drives the receptor uptake this proposal assumes it avoids, and the structure numbers cited for it are not in this card.
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.8898584842681885 | boltz-2 |
| ranking score | 0.6852999329566956 | 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{pep10561,
sequence = {GTSLSPPPESSGSRQQPGLSAPHSRQIPAPQGAVLVQREKDLPNYNWNSFGLRF},
target = {kiss1r},
author = {peptidemodel},
year = {2026},
status = {synthesized}
}