Comparison
FOXO4-DRI vs. Gonadorelin
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
33515-09-2
Molecular weight
3735 g/mol
1182.29 g/mol
Half-life
0.5 h
0.1 h
Sequence
D-Retro-Inverso-Variante eines FOXO4-Peptid-Fragments (LTLRKEPASEIAQSILEAYSQNGWANRRSGGKR — D-Aminosäuren in umgekehrter Sequenz)pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-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.
Gonadorelin
Gonadorelin acts as an agonist at the GnRH receptor on the gonadotroph cells of the pituitary and triggers release of the gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH). The temporal pattern of receptor exposure is decisive: pulsatile administration mimics the natural hypothalamic secretory rhythm and sustains LH/FSH release, whereas continuous exposure leads to receptor internalisation and desensitisation with subsequent paradoxical suppression of gonadotropins. The latter principle is exploited therapeutically by longer-acting GnRH agonists.
Evidence base
Highest evidence
Animal model
Human trial
Studies
3
4
of which in humans
0
4
Effects recorded
3
4
Open conflicts
1
1
Documented adverse events
1
2
Legal status
Full entries
Frequently asked questions
- What is the difference between FOXO4-DRI and Gonadorelin?
- FOXO4-DRI is classified as "Research other", while Gonadorelin 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. Gonadorelin: Gonadorelin is the synthetic decapeptide with an amino-acid sequence identical to endogenous gonadotropin-releasing hormone (GnRH/LHRH). Historically approved in several countries for diagnostic testing of pituitary function and for fertility indications (pump systems). A defining feature is the opposite effect of pulsatile versus continuous administration: pulsatile stimulates, continuous leads to receptor desensitisation. This page contrasts both neutrally and source-based — with no usage or dosing recommendation.
- Which peptide is better supported by science, FOXO4-DRI or Gonadorelin?
- The highest available evidence level is "Animal model" for FOXO4-DRI and "Human trial" for Gonadorelin. 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 Gonadorelin in Germany and the United States?
- Germany: FOXO4-DRI — Research only, Gonadorelin — Prescription. United States: FOXO4-DRI — Research only, Gonadorelin — Prescription. These are factual summaries with source and review date on the individual pages.