Comparison
FOXO4-DRI vs. Kisspeptin-10
Two peptides side-by-side — identity, evidence base, legal status and known adverse events.
Identity
Category
Research other
Research other
CAS no.
2074706-72-8
374675-21-5
Molecular weight
3735 g/mol
1302.44 g/mol
Half-life
0.5 h
0.07 h
Sequence
D-Retro-Inverso-Variante eines FOXO4-Peptid-Fragments (LTLRKEPASEIAQSILEAYSQNGWANRRSGGKR — D-Aminosäuren in umgekehrter Sequenz)H-Tyr-Asn-Trp-Asn-Ser-Phe-Gly-Leu-Arg-Phe-NH2Mechanism of action
FOXO4-DRI
FOXO4-DRI is the D-retro-inverso variant of a peptide fragment of the FOXO4 transcription factor. In senescent cells, FOXO4 is bound to p53, which suppresses p53-mediated apoptosis — the cells survive in a secreting 'zombie-like' state (senescence-associated secretory phenotype, SASP). The DRI peptide disrupts this FOXO4-p53 binding, freeing p53, and the senescent cell initiates apoptosis. Healthy cells are largely unaffected because p53 is not held back by FOXO4 in them. This selectivity was the central finding of the original 2017 publication.
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.
Evidence base
Highest evidence
Animal model
Human RCT
Studies
3
4
of which in humans
0
4
Effects recorded
3
4
Open conflicts
1
1
Documented adverse events
1
1
Legal status
Full entries
Frequently asked questions
- What is the difference between FOXO4-DRI and Kisspeptin-10?
- FOXO4-DRI is classified as "Research other", while Kisspeptin-10 is classified as "Research other". FOXO4-DRI: Synthetic peptide with D-Retro-Inverso structure (all amino acids as D-form, sequence reversed), developed in 2017 as an experimental senolytic candidate. Goal: selective apoptosis of senescent cells via disruption of the FOXO4-p53 interaction. So far evaluated exclusively preclinically. 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. This page contrasts both neutrally and source-based — with no usage or dosing recommendation.
- Which peptide is better supported by science, FOXO4-DRI or Kisspeptin-10?
- The highest available evidence level is "Animal model" for FOXO4-DRI and "Human RCT" for Kisspeptin-10. 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 FOXO4-DRI and Kisspeptin-10 in Germany and the United States?
- Germany: FOXO4-DRI — Research only, Kisspeptin-10 — Unapproved. United States: FOXO4-DRI — Research only, Kisspeptin-10 — Research only. These are factual summaries with source and review date on the individual pages.