Kisspeptin-10 10mg Peptide

Kisspeptin-10 is the C-terminal decapeptide of the KISS1 gene product, Tyr-Asn-Trp-Asn-Ser-Phe-Gly-Leu-Arg-Phe-NH2, corresponding to residues 112 to 121 of the human precursor (UniProt Q15726). It is C63H83N17O14 at 1,302.4 g/mol as the free base, CAS 374675-21-5, PubChem CID 25240297. Every naturally occurring kisspeptin isoform ends in this same ten-residue sequence, which is why kisspeptin-10 is described in the literature as the minimal fragment retaining full intrinsic activity at the kisspeptin receptor.

The compound has two discovery stories that took seven years to connect. In 1996 a group at the Jake Gittlen Cancer Research Institute in Hershey, Pennsylvania isolated a cDNA from melanoma cells whose metastatic capacity had been suppressed by transfer of chromosome 6, and named it KiSS-1 after the town's chocolate. In 2001 three laboratories independently deorphanised the receptor GPR54 and found the KiSS-1 product was its ligand. In 2003 two human genetics papers reported that loss-of-function mutations in that same receptor cause hypogonadotropic hypogonadism and pubertal failure, which moved a metastasis suppressor to the top of the reproductive hierarchy.

Kisspeptin-10 is not the isoform that produced most of the human clinical record. The Imperial College London programme that ran the in vitro fertilisation trigger trials, the intranasal work and the limbic imaging studies used kisspeptin-54. Kisspeptin-10 has its own human literature, principally from Edinburgh, Boston and Imperial, and the two peptides behave differently enough after peripheral administration that the distinction is the most important thing to get right about this compound.

Kisspeptin-10 is an agonist at KISS1R, the class A rhodopsin-like G protein coupled receptor previously catalogued under three separate names: GPR54, AXOR12 and hOT7T175. The human receptor is 398 residues, encoded on chromosome 19p13.3, and couples to Gq/11. Ligand binding activates phospholipase C, hydrolyses PIP2 to inositol trisphosphate and diacylglycerol, mobilises intracellular calcium and phosphorylates ERK1/2 and p38. Kotani and colleagues reported low nanomolar affinity at both rat and human GPR54 expressed in CHO-K1 cells in 2001, alongside arachidonic acid release, stress fibre formation and inhibition of cell proliferation.

C-terminal amidation is not a formatting detail. Binding affinity at the human receptor is 0.042 nM for kisspeptin-10 and 0.34 nM for kisspeptin-54, while a C-terminally unamidated form binds at 640 nM, roughly four orders of magnitude weaker. The terminal Arg-Phe-NH2 motif places kisspeptin in the RF-amide peptide family, though other members of that family including neuropeptide FF, prolactin-releasing peptide and neuropeptide Y do not activate KISS1R.

The physiological target is the GnRH neuron, not the pituitary gonadotrope. Thompson and colleagues demonstrated the separation in adult male rats in 2004: intracerebroventricular kisspeptin-10 dose-dependently raised plasma LH, a 3 nmol intracerebroventricular dose raised LH at 10, 20 and 60 minutes and testosterone at 20 and 60 minutes, and kisspeptin-10 released LHRH from hypothalamic explants in vitro. Applied directly to anterior pituitary fragments at 100 to 1000 nM, it released neither LH nor FSH. Whatever kisspeptin-10 does to gonadotropins, it does through the hypothalamus.

Downstream of the receptor, kisspeptin-10 produces a biphasic signal with an acute component lasting about five minutes and a prolonged component beyond thirty. GRK2 phosphorylates the receptor and recruits beta-arrestin, which uncouples it from Gq/11 and traffics it into clathrin-coated pits. Most receptors are then resensitised and recycled, a minority are degraded. That cycle is the molecular basis of the tachyphylaxis that dominates the practical pharmacology of this compound.

Lee and colleagues published KiSS-1 in the Journal of the National Cancer Institute in 1996. Transferring human chromosome 6 into the C8161 and MelJuSo melanoma lines suppressed their metastatic capacity by at least 95 percent without touching tumorigenicity, and subtractive hybridisation against the suppressed hybrids pulled out a single novel cDNA. KiSS-1 mRNA appeared only in non-metastatic melanoma cells, was undetectable in heart, brain, liver, lung and skeletal muscle, and was expressed most strongly in placenta. Transfecting the full-length cDNA back into C8161 cells suppressed metastasis in proportion to expression. The work was done at the Jake Gittlen Cancer Research Institute in Hershey, Pennsylvania, and the name is a play on the town's confectionery, with SS marking the suppressor sequence.

The receptor arrived from the other direction. GPR54 had been described in 1999 as an orphan G protein coupled receptor with roughly 40 percent homology to galanin receptors. In 2001 three groups deorphanised it. Ohtaki and colleagues at Takeda isolated a 54-residue C-terminally amidated peptide from human placenta, named it metastin, and showed it inhibited chemotaxis and invasion of receptor-transfected CHO cells and attenuated pulmonary metastasis of receptor-transfected B16-BL6 melanoma in mice. Kotani and colleagues in Brussels isolated 54, 14 and 13 residue peptides from the same tissue, named them kisspeptins, and characterised the signalling. Muir and colleagues published the same receptor as AXOR12. Three names for one receptor, all still in circulation.

Nothing in that decade suggested reproduction. That came in 2003 from two independent human pedigrees. De Roux and colleagues mapped a consanguineous family with five affected siblings to chromosome 19p13 and found a homozygous 155-nucleotide deletion in GPR54 spanning the intron 4 to exon 5 splice acceptor. Seminara and colleagues found a homozygous L148S substitution in one pedigree and compound heterozygous R331X and X399R mutations in an unrelated proband, showed both reduced inositol phosphate accumulation in transfected COS-7 cells, and phenotyped a Gpr54-deficient mouse that had isolated hypogonadotropic hypogonadism yet normal hypothalamic GnRH content and a preserved response to exogenous GnRH. The lesion was upstream of GnRH release, not in GnRH itself.

The genetics closed from both ends over the following decade. Teles and colleagues reported an activating GPR54 mutation, Arg386Pro, in a girl with idiopathic central precocious puberty, with prolonged intracellular signalling in vitro. Topaloglu and colleagues reported an inactivating mutation in KISS1 itself in a large consanguineous family with failure of pubertal progression, which had been the missing piece: until then only receptor mutations had been described in humans.

The four named isoforms are not analogues of one another. They are nested fragments of a single precursor, and their C-terminal ten residues are identical. Kisspeptin-54, also called metastin, is residues 68 to 121 of human KISS1. Kisspeptin-14 is 108 to 121, kisspeptin-13 is 109 to 121, and kisspeptin-10 is 112 to 121. Every one of them ends in Arg-Phe-NH2 and every one of them activates the same receptor through the same decapeptide contact surface. In isolated human coronary artery, kisspeptin-10, kisspeptin-13 and kisspeptin-54 were vasoconstrictors of comparable potency and efficacy, which is what identical pharmacophores should produce in a tissue bath.

In a living animal they diverge sharply, and the reason is not receptor pharmacology. D'Anglemont de Tassigny and colleagues gave systemic kisspeptin-54 or kisspeptin-10 to male mice and measured plasma LH at 10 minutes and at 2 hours. Kisspeptin-54 sustained LH release far longer. Measured directly, kisspeptin-54 had a bloodstream half-life of approximately 32 minutes against approximately 4 minutes for kisspeptin-10. The obvious explanation is clearance, so the authors tested it: repeating kisspeptin-10 injections every 10 minutes for an hour still failed to reproduce the sustained rise from a single kisspeptin-54 injection. Peripherally administered kisspeptin-54 raised c-Fos in GnRH neurons behind the blood brain barrier, and kisspeptin-10 did not. The data are consistent with kisspeptin-54 crossing that barrier and kisspeptin-10 being less able to.

In humans the gap narrows. Jayasena and colleagues ran the only direct equimolar comparison, giving healthy men three-hour intravenous infusions of vehicle, kisspeptin-10, kisspeptin-54 and GnRH at 0.1, 0.3 and 1.0 nmol/kg/h, five subjects per dosing group. At 1.0 nmol/kg/h the mean area under the LH curve was 10.81 plus or minus 1.73 h.IU/L for kisspeptin-10, 14.43 plus or minus 1.27 for kisspeptin-54 and 34.06 plus or minus 5.18 for GnRH. The two kisspeptin isoforms produced similar gonadotropin output at the doses tested, and GnRH was roughly three-fold more potent than kisspeptin-10 and two-fold more potent than kisspeptin-54. The rodent superiority of kisspeptin-54 did not clearly reproduce in a human intravenous infusion.

The practical consequence is a citation problem rather than a chemistry problem. The in vitro fertilisation trigger trials, the intranasal delivery work, the limbic imaging studies and the twice-weekly hypothalamic amenorrhoea protocol all used kisspeptin-54. Listings that attach those results to a vial of kisspeptin-10 are describing a different peptide. The kisspeptin-10 human record is real and separate: Edinburgh's pulse-frequency work, Boston's pulse-generator resetting, Imperial's dimorphism and chronic-administration studies.

Two hypothalamic kisspeptin populations do different jobs. In humans they sit in the infundibular nucleus and the rostral preoptic area, corresponding to the arcuate nucleus and the rostral periventricular area of the third ventricle in rodents. The infundibular and arcuate population coexpresses kisspeptin, neurokinin B and dynorphin, and is known by the acronym KNDy. The preoptic population does not.

KNDy neurons are the current best candidate for the GnRH pulse generator itself. Neurokinin B acting at NK3R stimulates the network and dynorphin acting at the kappa opioid receptor inhibits it, in an autosynaptic and paracrine loop that converts a tonic input into a rhythm. The output is pulsatile kisspeptin release onto GnRH neurons, which is what produces pulsatile GnRH. The two populations also read different steroid feedback: the KNDy population carries the negative feedback of estradiol and testosterone, while the preoptic population mediates the positive estrogen feedback that generates the preovulatory LH surge in females.

That division explains the sexual dimorphism in the human kisspeptin-10 data. Jayasena and colleagues found that women in the follicular phase did not raise gonadotropins to kisspeptin-10 at intravenous bolus doses up to 10 nmol/kg, subcutaneous bolus up to 32 nmol/kg, or infusion up to 720 pmol/kg/min, while the same women in the preovulatory phase responded to a 10 nmol/kg bolus, and men responded from 0.3 nmol/kg. Responsiveness tracks the steroid environment of the network rather than the amount of peptide delivered.

The same anatomy is why neurokinin B antagonism became a menopause therapy while kisspeptin agonism did not. KNDy neurons hypertrophy and upregulate kisspeptin gene expression after the loss of estrogen feedback, a finding first reported in postmenopausal women and ovariectomised monkeys, and they project into the hypothalamic thermoregulatory centre. Blocking the neurokinin B side of the loop is what reduces vasomotor symptoms. Kisspeptin-10 sits on the stimulatory side of the same circuit.

Gonadorelin is synthetic GnRH itself, pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2, a decapeptide acting at the GnRH receptor on anterior pituitary gonadotropes. Kisspeptin-10 is also a decapeptide, but the resemblance ends there: it acts one level higher, on GnRH neurons in the hypothalamus, and produces no pituitary effect on its own. Thompson and colleagues showed the boundary directly by applying kisspeptin-10 to isolated rat anterior pituitary fragments at 100 to 1000 nM and observing no LH or FSH release, while the same peptide released LHRH from hypothalamic explants.

Because of that, the two compounds test different things. A gonadorelin challenge probes whether the pituitary can respond. A kisspeptin challenge probes whether functional GnRH neurons exist to be driven, which is why kisspeptin is being investigated as a diagnostic of hypothalamic function. In men with congenital hypogonadotropic hypogonadism who had undergone spontaneous reversal, kisspeptin-10 boluses of 0.24 to 2.4 nmol/kg induced LH pulses within 30 minutes in those with sustained reversal but not in those who had relapsed. In unprimed patients a GnRH bolus produced a response where a 0.24 nmol/kg kisspeptin-10 bolus produced none.

Potency also differs, in GnRH's favour. In the equimolar three-hour infusion comparison, LH output was about three-fold higher on GnRH than on kisspeptin-10. The argument for the upstream peptide is not potency but pattern: kisspeptin acts on a neuronal population that still integrates steroid feedback, metabolic state and circadian input, so the GnRH it evokes retains more of the shape of endogenous secretion.

Both desensitise on continuous exposure, and this is where the mechanisms genuinely part company. Continuous gonadorelin downregulates the pituitary GnRH receptor, which is the mechanism long-acting agonists exploit to suppress the axis. Continuous kisspeptin desensitises KISS1R on the GnRH neuron through beta-arrestin recruitment and internalisation. The two are separable experimentally: in agonadal juvenile and adult male monkeys, a 98-hour intravenous kisspeptin-10 infusion peaked at 3 hours and declined by 12, after which a GnRH bolus still raised LH but a kisspeptin-10 bolus did not. The block was at the kisspeptin receptor, with the pituitary still responsive.

Kisspeptin-10 clears fast. Reported terminal half-life is approximately 3 minutes in the human literature and approximately 4 minutes measured directly in mouse bloodstream, against approximately 28 minutes for kisspeptin-54 in humans and approximately 32 minutes in mice. Dhillo and colleagues measured the kisspeptin-54 figure precisely during the first human study: 27.6 plus or minus 1.1 minutes, metabolic clearance rate 3.2 plus or minus 0.2 mL/kg/min, volume of distribution 128.9 plus or minus 12.5 mL/kg. No comparably detailed human pharmacokinetic dataset exists for kisspeptin-10.

Part of the reason for that clearance is written into the sequence. Takino and colleagues found that active MMP-2, MMP-9, MT1-MMP, MT3-MMP and MT5-MMP all cleave the Gly118-Leu119 bond of the KISS1 protein, and that the same bond is cleaved in the isolated decapeptide. In kisspeptin-10 numbering that is the Gly7-Leu8 bond, in the middle of the sequence. Digestion abolished ligand activity. A peptide whose only pharmacophore contains a matrix metalloproteinase site is not going to have a long circulating life, and this is also why MMP-resistant kisspeptin analogues became a design goal.

The receptor tires faster than the peptide clears. In women with hypothalamic amenorrhoea given kisspeptin-54 twice daily, LH responsiveness fell gradually and FSH responsiveness was nearly abolished by day 2. Moving the same peptide to a twice-weekly interval produced only partial desensitisation, and after 8 weeks reproductive hormones were significantly elevated against saline. The variable that mattered was the interval, not the amount.

The 2026 chronic subcutaneous kisspeptin-10 study made that explicit for this isoform. Fifteen healthy men received acute 8-hour subcutaneous infusions across 1.25 to 10.0 nmol/kg/h, which raised LH, FSH and testosterone dose-dependently against vehicle (P<.0001). A continuous 5-day infusion at 180 nmol/h then left gonadotropins indistinguishable from vehicle even though testosterone stayed up. Splitting delivery into daily 8-hour infusions at 150 nmol/h with 16 hours off sustained the gonadotropin rise across 12 days, and a 1 nmol/kg bolus at the end still evoked a response, confirming the receptor was functional rather than exhausted. Continuous exposure and intermittent exposure to the same compound produce opposite endocrine outcomes.

One caveat belongs with all of this. Tachyphylaxis is a feature of high-dose exogenous administration and may not describe endogenous signalling. Optogenetic activation of kisspeptin neurons in the rostral periventricular area of the third ventricle in female mice persistently stimulates GnRH neuronal firing without the same fade.

Twenty-two kisspeptin studies are registered on ClinicalTrials.gov, and the interventional ones cluster tightly around reproductive endocrinology. NCT05633966, a Phase 1 study of subcutaneous kisspeptin in patients with hypothalamic amenorrhoea and hypogonadotropic hypogonadism, has completed. NCT04648969, a Phase 2 study of prolonged pulsatile kisspeptin administration in hypogonadotropic hypogonadism, has completed. NCT02956447, a Phase 2 study in hyperprolactinaemia, has completed. Phase 2 recruitment continues under NCT05896293 in isolated hypogonadotropic hypogonadism and NCT07224438 in hypothalamic amenorrhoea, and a Phase 1 study using kisspeptin to quantify GnRH neuronal function in health and disease opened in 2026 under NCT07224490.

A metabolic arm ran in parallel and stalled. NCT04958109 evaluated kisspeptin-stimulated insulin secretion during an oral glucose tolerance test and completed; NCT05456854, using a hyperglycaemic clamp, and NCT04532801, using a mixed meal, were both terminated. The underlying human observation is modest: an intravenous kisspeptin-54 infusion at 1 nmol/kg/h for 2 hours in 15 healthy men raised mean post-glucose-load insulin secretion by 4.1 microunits/mL and improved the disposition index, while a later crossover study in 17 women with overweight or obesity found no effect on preprandial or postprandial insulin and glucose.

Appetite is a negative result worth stating plainly. Rodent studies have reported kisspeptin-10 reducing food intake in fasted mice and rats, but in humans an intravenous kisspeptin-54 infusion changed neither self-reported hunger on visual analogue scales nor objective food intake in healthy men, and a further study found no brain response to visual food stimuli. Whatever the rodent appetite data represent, it has not carried across into the human studies performed so far.

The kisspeptin-54 programme holds most of the headline clinical results. Jayasena and colleagues gave 53 women undergoing in vitro fertilisation a single subcutaneous kisspeptin-54 injection across 1.6 to 12.8 nmol/kg to trigger oocyte maturation after recombinant FSH and a GnRH antagonist; eggs were retrieved at 36 hours, fertilisation and embryo transfer occurred in 92 percent (49 of 53), and clinical pregnancy was 23 percent. Abbara and colleagues then ran a Phase 2 study in 60 women at high risk of ovarian hyperstimulation syndrome: oocyte maturation occurred in 95 percent, live birth per transfer across all doses was 45 percent, and no woman developed moderate, severe or critical hyperstimulation. Mills and colleagues reported in 2025 that intranasal kisspeptin-54 at 12.8 nmol/kg raised LH by a mean 4.3 IU/L above placebo in patients with hypothalamic amenorrhoea (P<0.001), with the formulation chemically stable for 60 days at 4 degrees Celsius. All three used the 54-residue isoform.

KISS1 and KISS1R are expressed well outside the hypothalamus: placenta, particularly syncytiotrophoblast, along with gonads, adipose tissue, pancreas, liver, small intestine, bone and limbic regions. The receptor is additionally detectable at lower levels in stomach, thymus, spleen, lung, heart, kidney and adrenal. That distribution is the source of most non-reproductive kisspeptin research, and most of it remains preclinical.

The placental biology is the closest thing to a second established role. Bilban and colleagues compared mRNA signatures of highly invasive first-trimester trophoblast against non-invasive term trophoblast, found KiSS-1 and its receptor enriched in the invasive population, and identified kisspeptin-10 in first-trimester trophoblast conditioned medium. Kisspeptin-10, and specifically not the longer isoforms, raised intracellular calcium in those cells and inhibited their migration in explant and transwell assays without touching proliferation. Trophoblast invasion and tumour metastasis are the same cell behaviour under different control, which is why one gene governs both.

The cardiovascular findings deserve more attention than they get in this category. Mead and colleagues localised GPR54 mRNA to the smooth muscle of aorta, coronary artery and umbilical vein, three vessels sharing a developmental origin, and colocalised receptor and peptide to vascular endothelium and to coronary atherosclerotic plaque. Kisspeptin-10 constricted isolated human coronary artery rings, with negative log EC50 of 7.89 plus or minus 0.24. The receptor distribution is described in the source paper as atherosclerosis-prone.

The limbic work is the origin of most consumer interest in this compound, and it used kisspeptin-54. Comninos and colleagues compared kisspeptin against vehicle in 29 healthy heterosexual young men under functional neuroimaging, and found enhanced limbic activity specifically to sexual and couple-bonding stimuli, correlations with psychometric measures of reward, drive, mood and sexual aversion, and attenuated negative mood. A 2025 human study reported that kisspeptin administration stimulated reproductive hormones without affecting anxiety. No equivalent neuroimaging dataset exists for kisspeptin-10.

The 1,302.4 g/mol figure and CAS 374675-21-5 both describe the free base of the human sequence. Lyophilised research peptide is almost always supplied as the acetate or trifluoroacetate salt, so net peptide content on a certificate of analysis will be a fraction of the gross vial mass. A certificate that does not state which mass it is quoting cannot be reconciled against one that does. This distinction is systematically absent from listings in this category.

The species question is specific to this compound and is almost never addressed. Human kisspeptin-10 is YNWNSFGLRF-NH2. Rat and mouse kisspeptin-10, from the rodent Kiss1 precursor, is YNWNSFGLRY-NH2, ending in tyrosine rather than phenylalanine. That is one residue and about 16 daltons of difference in a peptide of 1,302 daltons. A large fraction of the preclinical kisspeptin-10 literature used the rodent sequence, and a vial of the human sequence is not the peptide those experiments used. Any certificate should state which sequence it describes.

C-terminal amidation is the single most consequential quality attribute here, more so than for most peptides. The unamidated free acid binds the human receptor at 640 nM against 0.042 nM for the amide, roughly a four-order-of-magnitude loss. Incomplete amidation or hydrolysis of the terminal amide therefore produces a near-inactive impurity that is only 1 dalton heavier than the parent and will not separate cleanly on a routine gradient. High-resolution accurate-mass data, not unit-resolution mass spectrometry, is what distinguishes them.

Purity and identity answer different questions and should be reported separately. Purity is an HPLC area percentage against total chromatographic response; identity is a mass or sequence confirmation. Volta specifies 99 percent or above by HPLC for material in this class. A figure presented as purity by mass spectrometry has conflated the two measurements. Liquid chromatography with high-resolution mass spectrometry methods for kisspeptin and its analogues in serum and urine were published in 2026 for doping control purposes, which gives some indication of what characterising this peptide properly requires.

For storage, the well-characterised state is the lyophilised powder held cold, dry and protected from light, with repeated freeze-thaw cycles avoided. Reconstituted stability figures of 7 to 30 days at 2 to 8 degrees Celsius circulate widely in this category without a citation attached. No published stability study for kisspeptin-10 in bacteriostatic water was located during this review. The one solution-stability datapoint that does exist in the literature is for a different isoform in a different formulation: intranasal kisspeptin-54 was reported chemically stable for up to 60 days at 4 degrees Celsius.