Comparison
Kisspeptin-10 vs. MOTS-c
Two peptides side-by-side — identity, evidence base, legal status and known adverse events.
Identity
Category
Research other
Research other
CAS no.
374675-21-5
1627580-64-6
Molecular weight
1302.44 g/mol
2174.61 g/mol
Half-life
0.07 h
no data
Sequence
H-Tyr-Asn-Trp-Asn-Ser-Phe-Gly-Leu-Arg-Phe-NH2Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-ArgMechanism of action
Kisspeptin-10
Kisspeptin-10 comprises the ten C-terminal amino acids sufficient for binding to the KISS1R receptor (also GPR54). KISS1R is a G-protein-coupled receptor expressed predominantly on GnRH neurons in the hypothalamus. Activation signals through the Gq/11-phospholipase C pathway to release gonadotropin-releasing hormone (GnRH), which in turn drives the pituitary to secrete luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Kisspeptin signaling is regarded as an indispensable trigger of puberty; inactivating mutations in KISS1R are associated with absent puberty (idiopathic hypogonadotropic hypogonadism). Beyond the reproductive axis, KISS1R expression is described in limbic brain regions, discussed as a possible mechanism for the effects on sexual and emotional processing observed in imaging studies.
MOTS-c
MOTS-c arises from a short open reading frame located in the 12S rRNA region of the mitochondrial genome — unlike most peptides it is therefore not encoded by nuclear DNA. Mechanistically, preclinical work describes MOTS-c as modulating the folate cycle and the de novo purine biosynthesis tethered to it, thereby affecting the AMP/ATP ratio and, downstream, AMP-activated protein kinase (AMPK). Under metabolic stress, an AMPK-dependent translocation of the peptide into the cell nucleus and involvement in the regulation of stress-responsive genes (including via antioxidant-response-element-regulated transcription factors) have also been reported. These models derive predominantly from cell culture and rodents; the extent to which they reflect human physiology after administration of exogenous synthetic MOTS-c is not established by human studies.
Evidence base
Highest evidence
Human RCT
Human trial
Studies
4
4
of which in humans
4
1
Effects recorded
4
4
Open conflicts
1
1
Documented adverse events
1
1
Legal status
Full entries
Frequently asked questions
- What is the difference between Kisspeptin-10 and MOTS-c?
- Kisspeptin-10 is classified as "Research other", while MOTS-c is classified as "Research other". Kisspeptin-10: Kisspeptin-10 is the shortest bioactive fragment (10 amino acids) of the endogenous neuropeptide kisspeptin, encoded by the KISS1 gene. It acts as an agonist at the KISS1R (GPR54) receptor and stimulates hypothalamic GnRH neurons, driving release of LH and FSH. Kisspeptin is a master switch of puberty and reproduction and is studied in humans, notably by the group of Waljit Dhillo (Imperial College London), in reproductive disorders and in sexual and emotional brain processing. It is not an approved drug. MOTS-c: MOTS-c is a 16-amino-acid mitochondrial-encoded peptide (mitochondrial-derived peptide, MDP) whose open reading frame lies within the 12S rRNA region of mitochondrial DNA. In basic research (including the laboratories of Changhan Lee and Pinchas Cohen) it is described as a regulator of metabolic homeostasis and an activator of the AMPK pathway, and is sometimes discussed as an 'exercise mimetic'. The evidence comes almost entirely from cell and animal models; controlled human trials of MOTS-c as a therapeutic are lacking. It is not approved as a medicine anywhere and is traded on the grey market as a research chemical. This page contrasts both neutrally and source-based — with no usage or dosing recommendation.
- Which peptide is better supported by science, Kisspeptin-10 or MOTS-c?
- The highest available evidence level is "Human RCT" for Kisspeptin-10 and "Human trial" for MOTS-c. A higher evidence level means more robust data, but says nothing about suitability for an individual. The full body of evidence is on each peptide's own page.
- What is the legal status of Kisspeptin-10 and MOTS-c in Germany and the United States?
- Germany: Kisspeptin-10 — Unapproved, MOTS-c — Unapproved. United States: Kisspeptin-10 — Research only, MOTS-c — Unapproved. These are factual summaries with source and review date on the individual pages.