Comparison
FOXO4-DRI vs. Bremelanotide
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
189691-06-3
Molecular weight
3735 g/mol
1025.18 g/mol
Half-life
0.5 h
2.7 h
Sequence
D-Retro-Inverso-Variante eines FOXO4-Peptid-Fragments (LTLRKEPASEIAQSILEAYSQNGWANRRSGGKR — D-Aminosäuren in umgekehrter Sequenz)Ac-Nle-c[Asp-His-D-Phe-Arg-Trp-Lys]-OHMechanism 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.
Bremelanotide
Bremelanotide is a cyclic peptide that binds non-selectively to melanocortin receptors (MC1R through MC5R) — with highest affinity at MC4R in the central nervous system. The precise role of MC4R activation in sexual behaviour is not fully understood; animal data show effects on hypothalamic circuits. Peripheral effects (blood pressure, hyperpigmentation) are attributed to MC1R/MC2R.
Evidence base
Highest evidence
Animal model
Human RCT
Studies
3
5
of which in humans
0
5
Effects recorded
3
3
Open conflicts
1
1
Documented adverse events
1
2
Legal status
Full entries
Frequently asked questions
- What is the difference between FOXO4-DRI and Bremelanotide?
- FOXO4-DRI is classified as "Research other", while Bremelanotide 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. Bremelanotide: Synthetic cyclic heptapeptide acting as a non-selective melanocortin-receptor agonist. FDA-approved in 2019 as Vyleesi for hypoactive sexual desire disorder (HSDD) in pre-menopausal women. This page contrasts both neutrally and source-based — with no usage or dosing recommendation.
- Which peptide is better supported by science, FOXO4-DRI or Bremelanotide?
- The highest available evidence level is "Animal model" for FOXO4-DRI and "Human RCT" for Bremelanotide. 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 Bremelanotide in Germany and the United States?
- Germany: FOXO4-DRI — Research only, Bremelanotide — Unapproved. United States: FOXO4-DRI — Research only, Bremelanotide — Prescription. These are factual summaries with source and review date on the individual pages.