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Kisspeptin-10

Kisspeptin-10 (KP-10) is an endogenous decapeptide and the shortest biologically fully active C-terminus of the kisspeptin family; it activates KISS1R (GPR54) on hypothalamic GnRH neurons and thereby controls pubertal onset and pulsatile LH/FSH release. Exclusively clinical research material - no FDA/EMA approval.

Sexual Health & Libido · Not medical advice.

Evidence: Level 2 · early clinical research
Type
Single peptide
Category
Sexual Health & Libido
Administration
Injection
Vial code
KP10
Vial sizes
1 mg, 3 mg (lyophilisate, research reagent)
Brand names
None (research reagent; clinical studies use GMP custom synthesis, e.g. Bachem)
Half-life
~4 minutes (i.v.); markedly shorter than KP-54 (~28 min) - which is why clinical programs prefer KP-54 or more stable agonists

Mechanism of action
Acts as an agonist at KISS1R (GPR54), a Gq/11-coupled receptor on hypothalamic GnRH neurons; triggers intracellular Ca2+ and MAPK signaling and drives pulsatile GnRH release, which in turn elicits LH (strongly) and FSH (more weakly) from the anterior pituitary. In tumor models KP-10 additionally inhibits CXCR4 signaling.
Benefits & use
KP-10 is investigated as a physiological trigger for LH/FSH in hypogonadotropic hypogonadism, for stimulation of endogenous testosterone and estradiol release, and as a research tool in reproductive endocrinology and oncology. A clear sexual dimorphism in response has been documented.
Study status
Phase 1 pharmacology in healthy men (George 2011, JCEM) and women (Jayasena 2011, JCEM) plus ongoing trials of pulsatile administration in hypogonadotropic hypogonadism (NCT04648969). Clinical development has shifted toward the more stable KP-54 and the agonist MVT-602 (Phase 2 data, Abbara 2024). KP-10 itself is not FDA- or EMA-approved.
Dosing note
In published studies KP-10 was given almost exclusively i.v. as a bolus (0.5-3 nmol/kg) or as a multi-hour infusion, in newer protocols also subcutaneously in a pulsatile fashion. Research vials come as 1 mg or 3 mg lyophilisate. Peptipedia cannot provide a dosing recommendation.

Use in the injection calculator

Kisspeptin-10 (KP-10) is an endogenous decapeptide and the shortest biologically fully active fragment of the kisspeptin family. It binds the KISS1R (GPR54) receptor on hypothalamic GnRH neurons and acts as the master switch for pubertal onset and pulsatile LH/FSH release in humans. KP-10 is exclusively a clinical research peptide.

What is Kisspeptin-10?

The KISS1 gene on chromosome 1q32 encodes a 145-amino-acid precursor that is cleaved by prohormone convertases into several endogenous peptides: kisspeptin-54 (KP-54), KP-14, KP-13 and KP-10. All share the same C-terminal decapeptide H-Tyr-Asn-Trp-Asn-Ser-Phe-Gly-Leu-Arg-Phe-NH2 (MW ~1.3 kDa, CAS 374675-21-5), which is sufficient for full KISS1R activation. KP-10 was originally described as the 'metastin fragment' - metastin being the older name for KP-54 as a putative tumor suppressor.

How does Kisspeptin-10 work?

KP-10 binds KISS1R (GPR54) on kisspeptinergic neurons of the arcuate nucleus and the anteroventral periventricular region. Via Gq/11 it triggers intracellular calcium and MAPK signaling, driving pulsatile GnRH release. GnRH in turn stimulates the anterior pituitary to release:

  • LH (luteinizing hormone) - sharp, rapid, dose-dependent rise
  • FSH (follicle-stimulating hormone) - to a lesser extent
  • Downstream: testosterone (Leydig cells) and estradiol (granulosa cells)

In tumor models KP-10 can additionally suppress CXCR4 signaling - a secondary effect contributing to the metastasis-suppressive function originally attributed to the KISS1 gene product via KISS1R.

What is the evidence?

The clinical evidence for KP-10 rests on Phase 1 pharmacology in healthy volunteers, supplemented by larger KP-54 programs:

  • Men (George 2011, JCEM): i.v. bolus raised LH in a dose-dependent manner; 22.5-h infusion additionally increased FSH and testosterone (DOI 10.1210/jc.2011-0089).
  • Women (Jayasena 2011, JCEM): clear sexual dimorphism - weaker effect in the follicular phase, marked effect in the pre-ovulatory phase (DOI 10.1210/jc.2011-1408).
  • Puberty: Seminara 2003 (NEJM) first showed that inactivating KISS1R mutations cause hypogonadotropic hypogonadism and absent puberty.
  • Hypogonadotropic hypogonadism: ongoing pulsatile KP trial NCT04648969.
  • IVF trigger (KP-54 / MVT-602): Abbara group (Fertil Steril 2024) confirmed that the KISS1R agonist MVT-602 triggers oocyte maturation with substantially lower OHSS risk than hCG.

KP-10 itself has no FDA or EMA approval - it remains a clinical research peptide.

How is KP-10 administered?

In published studies almost exclusively parenterally:

  • Intravenously as a bolus (study range 0.5-3 nmol/kg) or as a multi-hour infusion
  • Subcutaneously in newer protocols - e.g. pulsatile delivery via pump in hypogonadotropic hypogonadism

Research vials are supplied as lyophilisate (1 mg or 3 mg). If you reconstitute or store peptide material, see the Peptipedia guide on peptide storage and the related walkthroughs. Peptipedia cannot give a dosing recommendation - any use belongs in medical hands.

KP-10 vs. KP-54 - what is the difference?

KP-54 is the longer, considerably more plasma-stable variant (half-life ~28 min) and is preferred in most clinical programs. KP-10 has comparable receptor affinity but only ~4 min half-life i.v. - it is cheaper to synthesize and is therefore the standard tool in pharmacological basic research. For the broader Peptipedia tools overview and comparative context, KP-10 nevertheless remains the reference substance.

Safety and open questions

In the studies conducted so far KP-10 has been well tolerated. Important open questions:

  • Tachyphylaxis - chronic dosing leads to KISS1R desensitization (documented for KP-54 under 2-week dosing).
  • Tumor biology - KP-10 inhibits CXCR4; the oncological relevance is not fully resolved.
  • No approved product - any use outside clinical trials is off-label and unstudied.

FAQ

Is Kisspeptin-10 the same as Metastin?

Metastin is the older name for KP-54, the tumor-suppressive KISS1 gene product. KP-10 carries the last 10 amino acids of metastin and is the minimal active form.

Can Kisspeptin-10 be taken orally?

No - as a peptide it is broken down in the gastrointestinal tract. Clinical research uses i.v. or s.c. routes.

Does KP-10 act differently in women than in men?

Yes - Jayasena 2011 showed a clear sexual dimorphism: LH/FSH rises are smaller in the follicular phase and markedly stronger in the pre-ovulatory phase.

Related peptides

PT-141 (Bremelanotide) Gonadorelin

Sources

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