Comparison
FOXO4-DRI vs. Leuprorelin
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
53714-56-0
Molecular weight
3735 g/mol
1209.4 g/mol
Half-life
0.5 h
3 h
Sequence
D-Retro-Inverso-Variante eines FOXO4-Peptid-Fragments (LTLRKEPASEIAQSILEAYSQNGWANRRSGGKR — D-Aminosäuren in umgekehrter Sequenz)Pyr-His-Trp-Ser-Tyr-D-Leu-Leu-Arg-Pro-NHEtMechanism 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.
Leuprorelin
Leuprorelin is a GnRH-receptor agonist. After binding to pituitary GnRH receptors, it first causes a transient surge in luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release — the so-called flare. With continuous, non-pulsatile exposure the receptors are downregulated and desensitized, suppressing gonadotropin secretion and consequently lowering sex steroids (testosterone or estradiol) to low levels. This mechanism underlies the literature-described use in hormone-dependent conditions.
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
3
Legal status
Full entries
Frequently asked questions
- What is the difference between FOXO4-DRI and Leuprorelin?
- FOXO4-DRI is classified as "Research other", while Leuprorelin 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. Leuprorelin: Leuprorelin (also leuprolide) is a synthetic nonapeptide analogue of gonadotropin-releasing hormone (GnRH/LHRH). It is an approved prescription medicine in several jurisdictions, including for advanced prostate cancer, endometriosis, uterine fibroids and central precocious puberty. This page neutrally summarizes the evidence base and legal status and is not a usage or dosing recommendation. This page contrasts both neutrally and source-based — with no usage or dosing recommendation.
- Which peptide is better supported by science, FOXO4-DRI or Leuprorelin?
- The highest available evidence level is "Animal model" for FOXO4-DRI and "Human RCT" for Leuprorelin. 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 Leuprorelin in Germany and the United States?
- Germany: FOXO4-DRI — Research only, Leuprorelin — Prescription. United States: FOXO4-DRI — Research only, Leuprorelin — Prescription. These are factual summaries with source and review date on the individual pages.