Bottom line
Kisspeptin-54 (KP-54), originally named metastin, is the longest biologically active cleavage product of the KISS1 metastasis-suppressor gene. It acts as an An entry with substantial scientific visibility or identity value. Biological rationale and non-human evidence do not establish patient benefit. परिभाषा का स्रोत: Scope and selection methodology · शब्दावली agonist at KISS1R (GPR54) to stimulate GnRH and subsequent LH/FSH release. KP-54 is A clinical-stage candidate with scientific or public relevance. Investigation is not approval, and a studied exposure is not a recommendation. परिभाषा का स्रोत: Scope and selection methodology · शब्दावली only — no FDA- or EMA-approved product was identified — with phase 1/2 trials in hypothalamic amenorrhea, hypogonadotropic hypogonadism, and as a potential fertility treatment. It has a longer plasma The time for the amount of a substance in the body to fall by half. परिभाषा का स्रोत: Neutral gloss; usage context: Routes, devices, and absorption primer · शब्दावली (28 min) than kisspeptin-10 (~4 min), making it the preferred isoform for most clinical studies.
Identity and composition
| Field | Verified information |
|---|---|
| Preferred name | Kisspeptin-54 |
| Key aliases | KP-54; metastin; KISS1 (68-121); human metastin |
| Molecular/sequence identity | 54-amino-acid peptide; C-terminal decapeptide (residues 45-54) = kisspeptin-10 |
| Modifications/form | C-terminal amidation; full-length KISS1 product |
| Stable identifiers | UniProt Q8NG95 (KISS1); IUPHAR/BPS ligand 1288 |
| Identity caveats | Human KP-54 sequence differs from other species, limiting translation. KP-54 and KP-10 are equipotent at KISS1R in vitro, but KP-54 has longer in vivo The time for the amount of a substance in the body to fall by half. परिभाषा का स्रोत: Neutral gloss; usage context: Routes, devices, and absorption primer · शब्दावली |
Development and approval status
| Jurisdiction | Status and indication | Product/source | As of |
|---|---|---|---|
| No jurisdiction | A clinical-stage candidate with scientific or public relevance. Investigation is not approval, and a studied exposure is not a recommendation. परिभाषा का स्रोत: Scope and selection methodology · शब्दावली; phase 1/2 clinical trials only | Research-grade peptide | 2026 |
Registered trials: NCT05633966 (KASPR, KP-10), NCT05896293 (KP-10), NCT04648969 (KP-10); intranasal KP-54 study (Abbara et al. 2025, EBioMedicine).
- UNITED STATES
- No UNITED STATES row is present in the source status table
- EU/EEA
- No EU/EEA row is present in the source status table
- UNITED KINGDOM
- No UNITED KINGDOM row is present in the source status table
- OTHER DOCUMENTED
- No jurisdiction: Investigational; phase 1/2 clinical trials only
Sport status: WADA: The 2026 List explicitly names kisspeptin and its agonist analogues under S2.2.1 as testosterone-stimulating peptides prohibited at all times in males. Kisspeptin stimulates endogenous GnRH release but is not itself a GnRH analogue.
Mechanism and pharmacology
Full agonist at KISS1R on GnRH neurons, stimulating pulsatile GnRH release. KP-54 has a plasma The time for the amount of a substance in the body to fall by half. परिभाषा का स्रोत: Neutral gloss; usage context: Routes, devices, and absorption primer · शब्दावली of ~28 min in humans (vs. ~4 min for KP-10), and a volume of distribution of ~129 mL/kg. Continuous infusion can produce desensitisation, whereas pulsatile administration maintains responsiveness. KP-54 is equipotent with KP-10 in vitro but produces greater AUC for gonadotropins in vivo due to longer half-life.
Evidence by claim
| Claim/indication | Stage | Grade | Best human evidence | Main result | Important limitations |
|---|---|---|---|---|---|
| LH/FSH stimulation in healthy humans | Phase 1 | B | Neither participants nor investigators know who receives the study material or the comparator. परिभाषा का स्रोत: Neutral gloss; usage context: Evidence grading methodology · शब्दावली, An inactive comparator used in a controlled study. परिभाषा का स्रोत: Neutral gloss; usage context: Evidence grading methodology · शब्दावली-controlled crossover (Dhirn et al. 2005) | i.v. KP-54 (4 pmol/kg/min × 90 min) significantly increased LH, FSH, and testosterone | Small n=6; acute only |
| Hypothalamic amenorrhea — LH pulsatilty | Phase 1/2 | C | Single-blind, dose-ranging (Jayasena 2013, PMID 24517142) | KP-54 infusion increased LH pulses 3-fold vs. vehicle in HA women | Small n=5; infusion only, no ovulation endpoint |
| Intranasal delivery feasibility | Phase 1 | C | A study in which participants are assigned to the study material or a comparator by chance. परिभाषा का स्रोत: Neutral gloss; usage context: Evidence grading methodology · शब्दावली crossover (Abbara 2025) | Intranasal KP-54 (12.8 nmol/kg) increased LH in healthy and HA subjects | Includes KP-54 not KP-10; early stage |
- Aग्रेड A: विशिष्ट लेबल वाले उपयोग के लिए स्थापित
- Bग्रेड B: मध्यम मानव साक्ष्य
- Cग्रेड C: प्रारंभिक मानव साक्ष्य
- Dग्रेड D: केवल प्रीक्लिनिकल
- Eग्रेड E: उपाख्यानात्मक/विपणन दावा
- Xग्रेड X: साक्ष्य दावे का खंडन करता है या समर्थन नहीं करता
Text alternative for the claim-evidence diagram. Each grade is defined below:
- A — Established for a specific labeled use
- 0 claims
- B — Moderate human evidence
- 1 claim: LH/FSH stimulation in healthy humans
- C — Preliminary human evidence
- 2 claims: Hypothalamic amenorrhea — LH pulsatilty; Intranasal delivery feasibility
- D — Preclinical only
- 0 claims
- E — Anecdotal/marketing claim
- 0 claims
- X — Evidence contradicts or does not support the claim
- 0 claims
Key studies
| Study | Design/population | Exposure studied | Endpoints and result | Limitations |
|---|---|---|---|---|
| Dhirn et al. (2005) | DBPC crossover; healthy men (n=6) | i.v. KP-54 4 pmol/kg/min × 90 min vs saline | LH 10.8 vs 4.2 IU/L; FSH and T also significantly increased | n=6; short duration |
| Jayasena et al. (2013) | Single-blind; women with HA (n=5) | i.v. KP-54 infusion (0.01-1.0 nmol/kg/h × 8 h) | Peak LH pulses 5.0/8h vs 1.6/8h (vehicle) | Small n; Administered into a vein. परिभाषा का स्रोत: Neutral gloss; usage context: Routes, devices, and absorption primer · शब्दावली not practical for chronic use |
| Abbara et al. (2025) | DBPC crossover A study in which participants are assigned to the study material or a comparator by chance. परिभाषा का स्रोत: Neutral gloss; usage context: Evidence grading methodology · शब्दावली; healthy men, women, HA patients | Intranasal KP-54 (3.2-25.6 nmol/kg) | LH rise within 30-45 min; no AEs | First intranasal data; small; device-dependent |
Dose and administration evidence
Approved labeled regimen
Not applicable — not approved.
Studied regimens (not recommendations)
Administered into a vein. परिभाषा का स्रोत: Neutral gloss; usage context: Routes, devices, and absorption primer · शब्दावली infusion: 0.01-1.0 nmol/kg/h (8 hours; research only).
Intravenous bolus: 0.3-25.6 nmol/kg (single dose).
Intranasal spray: 3.2-25.6 nmol/kg (single dose; research only).
Administered into the tissue layer under the skin. परिभाषा का स्रोत: Neutral gloss; usage context: Routes, devices, and absorption primer · शब्दावली infusion: 0.1-1.0 nmol/kg/h (8 hours).
What is not established
No established or recommended human dose.
Safety
Human-study signals
Well-tolerated in all reported human studies.
No serious adverse events.
Mild subjective warmth, flushing at high doses.
No nausea or vasomotor symptoms reported with intranasal KP-54.
Desensitisation with continuous exposure; mitigated by pulsatile delivery.
Unknowns and product-quality risks
No chronic safety data (>2 weeks exposure).
No carcinogenicity or reproductive toxicity studies.
Online "kisspeptin-54" products are unregulated and may not be pure or correctly dosed.
Interactions and special populations
Not studied in pregnancy, lactation, children.
Baseline oestradiol levels affect LH response magnitude in women.
No studies with concurrent hormonal contraception.
Regulatory, compounding, and sport notes
Approval: No FDA-approved product or EMA-authorized medicine was identified; status elsewhere requires a current national-register check.
The World Anti-Doping Agency; its Prohibited List classifies many peptides as prohibited substances in sport. परिभाषा का स्रोत: WADA and sport regulation brief · शब्दावली: The 2026 List explicitly names kisspeptin and its agonist analogues under S2.2.1 as testosterone-stimulating peptides prohibited at all times in males. Kisspeptin stimulates An entry with substantial scientific visibility or identity value. Biological rationale and non-human evidence do not establish patient benefit. परिभाषा का स्रोत: Scope and selection methodology · शब्दावली GnRH release but is not itself a GnRH analogue.
Compounding: No general exemption or lawful-compounding conclusion follows from A clinical-stage candidate with scientific or public relevance. Investigation is not approval, and a studied exposure is not a recommendation. परिभाषा का स्रोत: Scope and selection methodology · शब्दावली status; applicable rules are product-, jurisdiction-, and fact-specific.
Evidence gaps
Chronic safety and desensitisation risk.
Efficacy for ovulation induction (phase 2/3 needed).
Optimal formulation and route.
Comparison with standard gonadotropin therapy.
Search notes
Databases and registries: PubMed, ClinicalTrials.gov, IUPHAR/BPS Guide to Pharmacology
Search terms: kisspeptin-54, KP-54, metastin, kisspeptin, human clinical trial
Last searched: 2026-08-06
Inclusion emphasis: Human clinical studies, registered trials
Sources
Dhirn WS, et al. Kisspeptin-54 stimulates the HPG axis in human males. J Clin Endocrinol Metab. 2005;90(12):6609-15. PMID 16174713.
Jayasena CN, et al. Increasing LH pulsatility in HA using KP-54 infusion. J Clin Endocrinol Metab. 2014;99(2):E243-51. PMID 24517142.
Abbara A, et al. Intranasal KP-54 stimulates gonadotropin release. EBioMedicine. 2025. https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(25)00133-1/fulltext
Chan YM, et al. Direct comparison of kisspeptin-10, -54, and GnRH. Hum Reprod. 2015;30(8):1849-56. PMID 26089302.
IUPHAR/BPS Guide – kisspeptin-54 ligand ID 1288. https://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1288
UniProt Q8NG95 (KISS1 precursor).
WADA. 2026 Prohibited List. https://www.wada-ama.org/en/resources/world-anti-doping-program/prohibited-list
