Kisspeptin

Technical data

INN name

Kisspeptin

CAS

374675-21-5

Molecular formula

C63H83N17O14

Molecular weight

1302.46 g/mol

Identity and composition

Kisspeptin (Kisspeptin-10 / KP-10) is a bioactive decapeptide derived from the product of the KISS1 gene (metastin/kisspeptin-54), corresponding to its C-terminal residues 45-54. In research it is studied as an upstream regulator of the reproductive axis, capable of stimulating the physiological release of GnRH. Product for research use.

Chemical identity data (verifiable reference):

• CAS: 374675-21-5
• Molecular formula: C63H83N17O14
• Molecular weight: ~1302.5 g/mol
• Sequence: H-Tyr-Asn-Trp-Asn-Ser-Phe-Gly-Leu-Arg-Phe-NH2 (YNWNSFGLRF-NH2, C-terminal amidated)
• Synonyms: Kisspeptin-10, KP-10, Metastin (45-54), Kisspeptin 45-54, PubChem CID 25240297

It is offered in presentations of 5 mg y 10 mg.

Mechanism of action

Kisspeptin-10 is the minimal bioactive fragment of kisspeptin and acts as agonist of the G protein-coupled receptor KISS1R (GPR54). Its activation in the GnRH neurons of the hypothalamus stimulates the release of GnRH, which in turn triggers the pituitary secretion of LH and FSH, activating the hypothalamic-pituitary-gonadal (HPG) axis.

Unlike direct GnRH agonists, kisspeptin works as upstream regulator: exogenous administration induces a physiological and pulsatile release of GnRH, instead of an artificial sustained stimulation.

In models of hyperprolactinemia, where prolactin suppresses the expression of endogenous kisspeptin (many kisspeptin neurons express the prolactin receptor, but few GnRH neurons do), it has been observed that exogenous kisspeptin restores pulsatile LH secretion, suggesting that the GnRH neuronal network remains functionally intact (PMC9282259).

Pharmacokinetics

Native KP-10 is characterized by a short half-life, reported approximately between ~55 seconds and ~4 minutes, markedly shorter than that of kisspeptin-54 (KP-54: ~28 min to ~1.8 h) (PMC9125910).

This rapid kinetics favors intravenous bolus or pulsatile administration. In studies an IV bolus was used (for example, 0.24 nmol/kg), observing an LH response in less than 30 minutes (PMC9282259).

The long-acting synthetic analogues (TAK-448, TAK-683) were designed with much longer half-lives (~1.6-2.2 h and up to ~18 h, respectively), as an alternative for sustained effects (PMC9125910).

Scientific evidence

Kisspeptin-10 is a clinical/experimental research tool and not an approved drug. The available evidence comes mainly from small, early-phase studies (proof-of-concept), so its definitive therapeutic efficacy is not established (PMC9125910).

In these exploratory contexts, the following have been investigated, among others:

• Induction of ovulation and oocyte maturation in IVF, especially in patients at high risk of ovarian hyperstimulation syndrome (OHSS).
• Tests of GnRH neuronal function.
• Evaluation of puberty disorders (distinguishing physiological vs pathological hypogonadism).
• Hypothalamic amenorrhea and polycystic ovary syndrome (PCOS).

In hypothalamic amenorrhea, it was observed that chronic twice-daily administration produced complete receptor desensitization (PMC9125910). Overall, the evidence is mostly exploratory and preliminary in nature.

Research applications

Product for research use.

Ideal for research lines such as:

• Study of the HPG axis and KISS1R/GPR54 signaling in experimental models.
• Research on the pulsatile release of GnRH, LH, and FSH as an upstream regulator.
• Exploratory models of reproduction (IVF/OHSS, PCOS, hypothalamic amenorrhea) and of GnRH neuronal function at an early stage.
• Comparative characterization against KP-54 or long-acting analogs.

Not applicable for:

• Any use in humans, diagnosis, treatment, or consumption.
• Protocols that require sustained action from a single bolus, given its short half-life (KP-54 or the analogs are more appropriate for prolonged effects).
• Chronic/frequent dosing schedules without considering the risk of desensitization (tachyphylaxis).

Research protocols

The doses described correspond exclusively to research studies and are presented in a qualitative/hedged manner; they do not constitute a usage guideline.

In studies the route used was intravenous bolus, taking advantage of the short half-life of KP-10. For example, an IV bolus of 0.24 nmol/kg, with an LH response observed in under 30 minutes (PMC9282259).

It was further documented that chronic twice-daily administration in hypothalamic amenorrhea led to complete receptor desensitization, which highlights the importance of the administration pattern in experimental design (PMC9125910). The consulted literature provides no additional fixed-dose protocols by presentation (5 mg / 10 mg).

Reconstitution

Standard general laboratory guide (not a use indication): the lyophilized peptide is usually reconstituted with bacteriostatic water (sterile water with ~0.9% benzyl alcohol as preservative), which allows multiple withdrawals while maintaining relative sterility.

Usual handling recommendations:

• Allow the peptide vial to reach room temperature before reconstituting.
• Add the diluent, letting it run down the wall of the vial, without directing the stream directly onto the powder.
• Do not shake; swirl gently until fully dissolved.
• Calculate the diluent volume according to the desired concentration, considering the nominal 5 mg or 10 mg content of the vial.

For assays where the preservative may interfere, sterile water for injection may be preferred, assuming its single-use nature.

Stability and storage

General laboratory handling standard for peptides (not an indication for use):

• Lyophilized (unreconstituted): is the most stable form. It is typically stored refrigerated in the short term and frozen for long-term storage, protected from moisture and light.
• Reconstituted in solution: is less stable and must be kept refrigerated, being used within a relatively short timeframe.

Good practices: avoid repeated freeze-thaw cycles, aliquot where applicable to minimize handling of the stock, and keep the vials well closed. Since KP-10 is a decapeptide, careful handling is advisable to preserve its integrity.

Safety profile

Profile based on limited data from early-phase studies and small cohorts with short exposure; it does not constitute a safety evaluation for clinical use.

In these exploratory studies no increases in adverse events versus placebo were reported (with no significant changes in nausea, heart rate or blood pressure) nor serious adverse events, and a selective hypothalamic action was described without affecting GH, prolactin or TSH (PMC9125910).

Relevant warning: the chronic or frequent administration can cause receptor desensitization and loss of response (tachyphylaxis), observed with twice-daily dosing in hypothalamic amenorrhea (PMC9125910).

The safety data are limited to small populations and brief exposures, so the long-term profile is not characterized.

Comparative context

Within the kisspeptin family and its functional class:

• KP-10 vs KP-54: KP-10 is the minimal bioactive fragment, with potency comparable to KP-54 for activating KISS1R, but with a much shorter half-life. For this reason, KP-54 is preferable when sustained effects via bolus are sought.
• Long-acting analogs (TAK-448, TAK-683): were designed specifically to prolong the duration of action relative to native KP-10.
• Compared to direct GnRH agonists: kisspeptin acts upstream, on GnRH neurons, generating a more physiological release and, in IVF protocols, being associated with a lower risk of OHSS (PMC9125910).

The choice between these molecules depends on the experimental objective: rapid, pulsatile action (KP-10) versus sustained exposure (KP-54 or analogs).

History and development

Kisspeptin-10 is identified as the C-terminal decapeptide (residues 45-54) derived from the gene product KISS1, whose complete peptide is metastin/kisspeptin-54. It corresponds to the minimal fragment capable of activating the KISS1R receptor (GPR54), which made it a key tool for studying the role of the kisspeptin-GnRH pathway in reproduction.

Its subsequent development led to the design of long-acting synthetic analogs (TAK-448 and TAK-683), explored separately to overcome the short half-life of native KP-10. It remains an early-phase research reagent and not an approved drug (PMC9125910).

FAQ

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Average rating: 4.9 out of 5, based on 7 customer ratings.

Certificate of analysis per batch

Kisspeptin batch with certificate of analysis published in the COA catalog:

• Lot EXO010626146B — 5 mg, issued 2026-05-30

Scientific references (4)

Peer-reviewed literature on Kisspeptin, with its PubMed identifier where available:

• Kisspeptin and Endometriosis-Is There a Link? (Meczekalski B et al. · Journal of clinical medicine · 2024) PMID 39768606.
• The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54 (Kotani, et al. · Journal of Biological Chemistry · 2001) PMID 11457843.
• The GPR54 gene as a regulator of puberty (Seminara, et al. · The New England Journal of Medicine · 2003) PMID 14573733.
• Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males (Dhillo, et al. · The Journal of Clinical Endocrinology & Metabolism · 2005) PMID 16174713.

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