Kisspeptin-54 Research, Specifications & Scientific Information

Introduction

Kisspeptin-54 is the form of kisspeptin that actually circulates in human blood, and it is the form that has been given to people. Its shorter relative Kisspeptin-10 is the C-terminal fragment that carries the receptor-binding motif; this is the whole peptide, 54 residues, originally described under the name metastin.

What makes its clinical record distinctive is where in the reproductive axis it acts. Every conventional way of driving a luteinising hormone surge works at or below the pituitary. This peptide works above it, on the hypothalamic neurons that release gonadotropin-releasing hormone ^[1]. The surge it produces is therefore the body's own, in the body's own shape — and an academic group at Imperial College London spent a decade testing whether that difference matters, first in healthy volunteers and then as a trigger for egg maturation in in vitro fertilisation ^{[3, 5]}.

The answer, so far, is that it is feasible and that the trials are small. Sixty participants in the largest, open-label, from one centre. No commercial development programme is on record and the compound is approved nowhere.

What Is Kisspeptin-54?

Kisspeptin-54 is a 54-residue peptide encoded by the KISS1 gene, described as the major circulating isoform of kisspeptin in humans ^[3]. The gene's product is cleaved into several peptides of different lengths — 54, 14, 13 and 10 residues — which share an identical amidated C-terminal decapeptide and differ in what precedes it.

That shared C-terminus is the functional part. It is an RFamide motif, and the amide is required for receptor activation: every biologically active kisspeptin works through the same terminal sequence at the same receptor, KISS1R, formerly called GPR54. The longer isoforms are not more potent at the receptor; they persist longer in the circulation, which is a pharmacokinetic difference rather than a pharmacodynamic one and is the practical reason the 54-residue form was chosen for the clinical trigger studies.

The substance is registered as a protein in the FDA/NCATS Global Substance Registration System under UNII 2VG74ZW2K5, with CAS registry number 388138-21-4 and PubChem compound identifier 71306396.

It is not approved by the U.S. Food and Drug Administration for any indication, and no marketing application for it is on record in the United States. Every human administration on record has been under an investigator-led research protocol.

Kisspeptin-54 Specifications

Kisspeptin-54 is the major circulating isoform of kisspeptin in humans and the peptide originally described under the name metastin. The FDA/NCATS Global Substance Registration System classifies it as a protein and records it under UNII 2VG74ZW2K5 with CAS registry number 388138-21-4; PubChem carries the same substance under compound identifier 71306396 with molecular formula C258H401N79O78 and average mass 5857 g/mol. The full 54-residue sequence is not reproduced here in single-letter code because no public register queried for this page publishes it as a machine-readable string against those identifiers; what is stated instead is the part that determines the pharmacology. All biologically active kisspeptins share the same C-terminal RFamide decapeptide, which is itself kisspeptin-10, and the amide at that C-terminus is required for receptor activation. The shorter and longer isoforms therefore act at the same receptor through the same terminal motif and differ chiefly in how long they persist in plasma.

Values that a public register does not carry are shown as not publicly characterised rather than estimated. Identifiers are reference values; the certificate of analysis supplied with a laboratory order is the record for a given lot.

How Does Kisspeptin-54 Work?

The receptor is KISS1R, a Gq/11-coupled class A G protein-coupled receptor. Its position in the reproductive axis is what makes the pharmacology interesting.

KISS1R is expressed on hypothalamic gonadotropin-releasing hormone neurons. Kisspeptin binding stimulates those neurons to release GnRH, and GnRH in turn drives luteinising hormone and follicle-stimulating hormone secretion from the anterior pituitary ^[1]. The peptide therefore never touches the pituitary directly. It operates one step further up.

The importance of that step was established genetically before it was established pharmacologically: people carrying mutations that inactivate kisspeptin signalling are infertile ^[3]. A pathway whose loss abolishes reproductive function is a pathway whose stimulation is worth examining, and that is the logic the whole programme rests on.

The practical consequence, and the hypothesis the trigger trials were built to test, is the shape of the resulting hormone release. A GnRH receptor agonist such as triptorelin or gonadorelin stimulates the pituitary directly and for as long as it is present. Acting through endogenous GnRH neurons instead produces a surge governed by the hypothalamus's own dynamics — shorter, self-limiting, and closer to what happens in an unstimulated cycle. Whether that translates into a clinically meaningful difference is exactly what the ovarian hyperstimulation work was asking.

Kisspeptin-54 Mechanism of Action

The mechanism above is established from human physiology rather than from receptor or cell-culture work on this specific isoform. No in vitro characterisation of kisspeptin-54 was located for this page, and none is claimed: the receptor pharmacology of the kisspeptin family has been characterised principally with the decapeptide, and it is summarised on the Kisspeptin-10 entry.

What can be said about this isoform specifically is that the responses measured in humans are consistent with KISS1R agonism upstream of GnRH — gonadotropin release in men ^[1], increased luteinising hormone pulsatility in women ^[2], and an infusion response that correlates with basal oestradiol ^[6], which is what an upstream stimulus acting on an axis with intact feedback would be expected to produce.

What Is Kisspeptin-54 Being Researched For?

• Oocyte maturation triggering in in vitro fertilisation — the principal application, tested first in a single-arm study and then in a phase 2 randomised trial ^{[3, 5, 4]}.
• Prevention of ovarian hyperstimulation syndrome — the specific clinical problem that motivated the trigger work ^[5].
• Reproductive axis physiology in healthy volunteers — gonadotropin responses in men ^[1], luteinising hormone pulsatility in women ^[2], and the relationship between response and basal oestradiol ^[6].

Each of those is investigator-led clinical research in defined populations under protocol. None of it is research into, or evidence about, research-grade material supplied for laboratory use.

Human Research on Kisspeptin-54

Human clinical research

Results from pharmaceutical clinical trials describe the investigational material and populations used in those studies and should not be interpreted as establishing the effects of research-grade materials offered for laboratory use.

First administration in human males, 2005

Design and result as reported. The study set out to determine the effects of elevating circulating kisspeptin in men. Administration stimulated the hypothalamic-pituitary-gonadal axis, establishing in humans what rodent and primate work had indicated ^[1].

Weight. This is a physiological demonstration in a small volunteer group, and it is the foundation of everything that followed. It shows that the pathway is stimulable in people; it establishes nothing therapeutic.

Luteinising hormone pulsatility in healthy women, 2013

Design. A single subcutaneous bolus injection in healthy women, with luteinising hormone pulsatility as the measured outcome — a finer-grained question than total hormone concentration ^[2].

Result as reported. A single injection temporarily increased luteinising hormone pulsatility ^[2].

Why pulsatility rather than concentration. The reproductive axis encodes information in pulse frequency, not only in amount. A stimulus that raises mean concentration while flattening pulsatility acts differently on the axis from one that preserves it, and this study was designed to tell those apart.

Egg maturation trigger in in vitro fertilisation, 2014

Population. 53 women undergoing in vitro fertilisation, after superovulation with recombinant follicle-stimulating hormone and a GnRH antagonist to prevent premature ovulation ^{[3, 4]}.

Endpoint and design. A single subcutaneous injection at one of four amounts — 1.6 nmol/kg (n = 2), 3.2 nmol/kg (n = 3), 6.4 nmol/kg (n = 24) and 12.8 nmol/kg (n = 24) — with eggs retrieved transvaginally 36 hours later. The primary outcome was egg maturation; eggs were then fertilised by intracytoplasmic sperm injection with transfer of one or two embryos ^[3].

Result. Egg maturation occurred at every amount tested, and the mean number of mature eggs per participant generally rose with the amount given. Fertilisation and embryo transfer occurred in 92% of participants (49 of 53). Biochemical pregnancy occurred in 40% (21 of 53) and clinical pregnancy in 23% (12 of 53) ^[3].

Limitations. Single-arm and open-label, with no comparator against a conventional trigger. Two of the four groups contained fewer than five participants, so the apparent relationship between amount and response rests largely on the two larger groups. Pregnancy rates from a single-arm study in a selected population cannot be compared with published rates from other protocols.

Phase 2 trial in women at high risk of ovarian hyperstimulation syndrome, 2015

Population. 60 women at high risk of developing ovarian hyperstimulation syndrome, at a single in vitro fertilisation unit in London during 2013–2014 ^[5].

Endpoint and design. A phase 2, multi-amount, open-label randomised trial using an adaptive design for allocation across four amounts — 3.2 nmol/kg (n = 5), 6.4 nmol/kg (n = 20), 9.6 nmol/kg (n = 15) and 12.8 nmol/kg (n = 20) — after a standard recombinant FSH and GnRH antagonist protocol. The primary outcome was oocyte yield, defined as the percentage of mature oocytes retrieved from follicles of 14 mm or more on ultrasound; secondary outcomes were rates of ovarian hyperstimulation syndrome and of pregnancy ^[5].

Result. Oocyte maturation occurred in 95% of women. The highest oocyte yield, 121%, followed 12.8 nmol/kg — 69% greater than after 3.2 nmol/kg, with a confidence interval from −16% to +153%. Across all amounts, biochemical pregnancy, clinical pregnancy and live birth rates per transfer (n = 51) were 63%, 53% and 45%; the highest rates followed 9.6 nmol/kg, at 85%, 77% and 62%. No woman developed moderate, severe or critical ovarian hyperstimulation syndrome ^[5].

Limitations. Open-label, single-centre, 60 participants, no comparator arm. The confidence interval on the central yield comparison spans zero, which the authors report. The absence of moderate or worse ovarian hyperstimulation syndrome in 60 women is encouraging and is not the same as a demonstrated reduction against an alternative trigger, because no alternative was administered. The authors' own conclusion is that the approach is promising.

Infusion study in women, 2016

Design and result as reported. Subcutaneous infusion stimulated gonadotrophin release in women, and the magnitude of the response correlated with basal oestradiol concentrations ^[6] — evidence that the response depends on the endocrine state of the axis at the time, not only on the amount administered.

How the evidence stands overall

Coherent, physiologically well-grounded and small. The human work comes largely from one academic group; the largest trial enrolled 60 participants; none of the trigger studies was blinded or controlled against an active comparator. A 2017 review describes the approach as promising ^[7], which remains the accurate summary.

Current Research Status

Status as of September 22, 2026. This block is rendered from maintained fields, not from prose, so it cannot go stale in one place and stay current in another.

Kisspeptin-54 vs Related Compounds

Against Kisspeptin-10

Kisspeptin-10 is the C-terminal decapeptide of the same gene product and carries the same receptor-binding motif. The difference is persistence in plasma rather than receptor pharmacology, and it is why the longer isoform was used in the trigger studies ^[3]. Most of the receptor-level characterisation in this family was done with the decapeptide.

Against GnRH and its analogues

Gonadorelin is GnRH itself and triptorelin a long-acting GnRH receptor agonist; both act at the pituitary. This peptide acts on the hypothalamic neurons that release GnRH, one step upstream ^[1]. That single difference in level of action is the entire rationale for studying it as a trigger.

Against human chorionic gonadotropin

The conventional trigger in assisted reproduction acts at the luteinising hormone receptor and persists for days, which is part of why ovarian hyperstimulation syndrome occurs. The comparison is implicit throughout this literature; it has not been made directly in a randomised trial of the two, so no comparative statement is made here.

Evidentiary position

The compound has genuine human data, a clearly defined receptor, and a mechanism supported by human genetics ^[3]. It also has no approval, no registered commercial programme, and no trial larger than sixty people.

No comparison of effect between these compounds is made on this page.

Chemical & Molecular Characteristics

A peptide at the boundary of being a protein. At 54 residues and roughly 5.9 kDa, this molecule is large enough that the FDA/NCATS register classifies it as a protein rather than as a small peptide. Molecular formula C258H401N79O78 and average mass 5857 g/mol are recorded under PubChem compound identifier 71306396, with CAS registry number 388138-21-4 and UNII 2VG74ZW2K5.

The C-terminal amide is not optional. All kisspeptins share an amidated RFamide C-terminus, and that amide is required for receptor activation. A preparation in which the C-terminal amide has hydrolysed to the free acid differs from the intended molecule by one dalton and is not an agonist. This is the single most consequential analytical point about the compound, and it is not resolved by a routine mass measurement on a 5.9 kDa species, where one dalton is well inside the width of the isotope envelope.

Length brings the synthesis burden. A 54-residue peptide made by solid-phase synthesis accumulates deletion sequences — chains missing one residue — as its characteristic impurity. Those differ from the target by roughly 2% of its mass and co-elute closely. Confirming the sequence of a peptide this long requires enzymatic digestion and mapping, not an intact-mass measurement.

No single-letter sequence is published against the registry identifiers queried for this page. The specification table therefore records the sequence descriptively rather than as a string. What is stated — that the molecule is KISS1 residues 68 to 121 with an amidated C-terminus ending in the kisspeptin-10 decapeptide — is the part that determines its pharmacology, and it is left at that rather than completed from an unverified source.

Solubility and adsorption. Peptides of this size and charge distribution adsorb appreciably to glass and to some plastics from dilute aqueous solution, so nominal and actual concentrations can diverge in dilute preparations. This is a general property of peptides in this size range rather than a peculiarity of this one.

Frequently Asked Questions

Scientific References

1. Dhillo WS, Chaudhri OB, Patterson M, et al.. Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males The Journal of clinical endocrinology and metabolism; 2005. PMID 16174713 doi:10.1210/jc.2005-1468
2. Jayasena CN, Comninos AN, Veldhuis JD, et al.. A single injection of kisspeptin-54 temporarily increases luteinizing hormone pulsatility in healthy women Clinical endocrinology; 2013. PMID 23452073 doi:10.1111/cen.12179
3. Jayasena CN, Abbara A, Comninos AN, et al.. Kisspeptin-54 triggers egg maturation in women undergoing in vitro fertilization The Journal of clinical investigation; 2014. PMID 25036713 doi:10.1172/JCI75730
4. The Use of the Hormone Kisspeptin in 'in Vitro Fertilisation' (IVF) Treatment 2012. NCT01667406
5. Abbara A, Jayasena CN, Christopoulos G, et al.. Efficacy of Kisspeptin-54 to Trigger Oocyte Maturation in Women at High Risk of Ovarian Hyperstimulation Syndrome (OHSS) During In Vitro Fertilization (IVF) Therapy The Journal of clinical endocrinology and metabolism; 2015. PMID 26192876 doi:10.1210/jc.2015-2332
6. Narayanaswamy S, Jayasena CN, Ng N, et al.. Subcutaneous infusion of kisspeptin-54 stimulates gonadotrophin release in women and the response correlates with basal oestradiol levels Clinical endocrinology; 2016. PMID 26572695 doi:10.1111/cen.12977
7. Kasum M, Franulić D, Čehić E, et al.. Kisspeptin as a promising oocyte maturation trigger for in vitro fertilisation in humans Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology; 2017. PMID 28393578 doi:10.1080/09513590.2017.1309019

Every identifier above is resolved against PubMed, Crossref or ClinicalTrials.gov at build time, and the title returned by the register is compared with the title stored here. A page does not publish if a reference fails to resolve.

Research-Use Information

For in vitro research use only. This material is a laboratory reagent. It is not a drug, food, dietary supplement, or cosmetic and is not for human or veterinary use, including ingestion, injection, or any other administration. No information on this page describes or implies any effect in humans or animals. Sold only to researchers under our Terms of Sale.