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 endogenous agonist at KISS1R (GPR54) to stimulate GnRH and subsequent LH/FSH release. KP-54 is investigational 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 half-life (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 half-life |
Development and approval status
| Jurisdiction | Status and indication | Product/source | As of |
|---|---|---|---|
| No jurisdiction | Investigational; 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).
Mechanism and pharmacology
Full agonist at KISS1R on GnRH neurons, stimulating pulsatile GnRH release. KP-54 has a plasma half-life 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 | Double-blind, placebo-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 | RCT 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 |
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; intravenous not practical for chronic use |
| Abbara et al. (2025) | DBPC crossover RCT; 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)
Intravenous 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).
Subcutaneous 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.
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.
Compounding: No general exemption or lawful-compounding conclusion follows from investigational 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