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Kisspeptin-10

KP-10Kisspeptin-10 (human)Metastin (45-54)Metastin 45-54Human metastin 45-54KiSS-1 (112-121)

Kisspeptin-10 (KP-10) is an investigational decapeptide and the minimal active fragment of kisspeptin/metastin that activates the KISS1R (GPR54) receptor to stimulate GnRH and downstream LH/FSH release in the reproductive hormone axis.

Sequence fingerprint

YNWNSFGLRF

  • Nonpolar5
  • Polar4
  • Basic (+)1
  • 10 residues

Tyr-Asn-Trp-Asn-Ser-Phe-Gly-Leu-Arg-Phe-NH2 (C-terminally amidated decapeptide)

Overview

Kisspeptin-10 (KP-10), also known as metastin (45-54), is a 10-amino-acid peptide corresponding to the C-terminal end of the larger kisspeptin/metastin protein encoded by the KISS1 gene. It is the minimal fragment needed to activate the kisspeptin receptor KISS1R (also called GPR54, and historically AXOR12 / hOT7T175).

When KISS1R is activated on hypothalamic GnRH neurons, it stimulates the release of gonadotropin-releasing hormone (GnRH), which signals the anterior pituitary to secrete luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Because of this, kisspeptin sits near the top of the hypothalamic-pituitary-gonadal (reproductive) axis and has been studied as a tool for probing and modulating reproductive hormone signaling.

Kisspeptin-10 has a very short circulating half-life (~4 minutes), so any effect it has on gonadotropin release is brief and transient. The longer 54-amino-acid form, kisspeptin-54, sustains LH release for considerably longer (its plasma half-life is roughly 32 minutes), which is why much human clinical work uses KP-54 rather than KP-10.

In research, kisspeptin-10 is used as a reference agonist to characterize KISS1R signaling and newer receptor agonists, and kisspeptin compounds have been investigated in early-phase human studies for conditions such as hypothalamic amenorrhea, for triggering oocyte maturation in assisted reproduction, and for sexual brain processing in hypoactive sexual desire disorder.

Regulatory note: Kisspeptin-10 is not an approved medicine in the US, EU, UK, or elsewhere. It is an investigational/research-only substance; in October 2024 the FDA's Pharmacy Compounding Advisory Committee voted against permitting it for pharmacy compounding, citing insufficient safety and efficacy data. Material sold by chemical suppliers is labeled "research use only" and not for human consumption. No claims of safety or efficacy for unsupervised human use are supported by the available evidence.

Chemistry: C63H83N17O14, molecular weight ~1302.4 g/mol, CAS 374675-21-5, PubChem CID 25240297. Sequence: Tyr-Asn-Trp-Asn-Ser-Phe-Gly-Leu-Arg-Phe-NH2 (YNWNSFGLRF), a C-terminally amidated decapeptide.

Mechanism, evidence & status

Kisspeptin-10 is the C-terminal decapeptide fragment of the KISS1 gene product (kisspeptin/metastin) and the minimal sequence required to activate the receptor KISS1R (also called GPR54). In animal and human studies, receptor activation on hypothalamic GnRH neurons stimulates GnRH release, which in turn drives secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the anterior pituitary. Reported circulating half-life is very short (roughly 4 minutes), so its effect on gonadotropin release is brief and transient relative to the longer kisspeptin-54.

Human evidence
Preclinical and early-phase human research (Phase 1/2 clinical studies); no approved indication
Regulatory status
Investigational research peptide. NOT approved by the FDA, EMA, MHRA, or any major regulator as a medicine, and not an authorized therapeutic product. In October 2024 the FDA's Pharmacy Compounding Advisory Committee voted to exclude kisspeptin-10 from the bulk drug substances permitted for compounding, citing insufficient safety and efficacy data. Studied only in academic and clinical-trial settings; sold elsewhere strictly as a "research use only" / not-for-human-use chemical.
Research applications
  • Used as a research tool to probe KISS1R/GPR54 signaling and the kisspeptin-GnRH-gonadotropin reproductive axis.
  • Investigated in early clinical research for stimulating LH/FSH release in reproductive disorders such as hypothalamic amenorrhea and for triggering oocyte maturation in assisted-reproduction contexts.
  • Explored in human neuroimaging/behavioral studies examining kisspeptin's effects on sexual and emotional brain processing (e.g., hypoactive sexual desire disorder).
  • Serves as a reference agonist in pharmacology for characterizing newer KISS1R agonists (e.g., MVT-602).
Safety considerations
  • Not an approved drug; no established safety profile for unsupervised human use, and quality/purity of research-sourced material is unverified (PubChem CID 25240297; CAS 374675-21-5).
  • In controlled clinical research, single doses of kisspeptin have generally been reported as well tolerated, but data come from monitored trial settings and do not establish safety outside them (PMC randomized trials, e.g. PMC9898824).
  • Because it acts on the reproductive (GnRH/LH/FSH) axis, off-target hormonal effects are plausible; long-term and repeated-dosing safety in humans is not established.
  • Very short plasma half-life (~4 min) means peripheral effects on hormone release are brief and transient (PMC5413024).
References
  1. [1]PubChem Compound: Kisspeptin-10 (CID 25240297)PubChem (NCBI)
  2. [2]Mechanistic insights into the more potent effect of KP-54 compared to KP-10 in vivo (half-life, KISS1R/GnRH mechanism)PMC / PLoS ONE
  3. [3]Effects of Kisspeptin on Sexual Brain Processing and Penile Tumescence in Men With HSDD: A Randomized Clinical TrialPMC / JAMA Network Open
  4. [4]Kisspeptin-10 (human), CAS 374675-21-5 — Guide to Pharmacology / IUPHAR ligand recordIUPHAR/BPS Guide to Pharmacology