Comparison
FOXO4-DRI vs. Melanotan II
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
121062-08-6
Molecular weight
3735 g/mol
1024.18 g/mol
Half-life
0.5 h
1 h
Sequence
D-Retro-Inverso-Variante eines FOXO4-Peptid-Fragments (LTLRKEPASEIAQSILEAYSQNGWANRRSGGKR — D-Aminosäuren in umgekehrter Sequenz)Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-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.
Melanotan II
Melanotan II binds non-selectively to all five melanocortin-receptor subtypes (MC1R-MC5R). Via MC1R in melanocytes, eumelanin synthesis is stimulated (pigmenting effect). Via MC4R and MC3R in the CNS, appetite, sexual function and blood pressure are modulated. The cyclic structure and D-amino acids increase stability compared to natural α-MSH.
Evidence base
Highest evidence
Animal model
Human trial
Studies
3
9
of which in humans
0
5
Effects recorded
3
4
Open conflicts
1
1
Documented adverse events
1
6
Legal status
Full entries
Frequently asked questions
- What is the difference between FOXO4-DRI and Melanotan II?
- FOXO4-DRI is classified as "Research other", while Melanotan II 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. Melanotan II: Cyclic hepta-peptide and non-selective melanocortin-receptor agonist. Originally researched at the University of Arizona as a sun-protection concept — never approved as a medicine. Widespread on the black market; regulatory warnings for cardiovascular and oncological risks. This page contrasts both neutrally and source-based — with no usage or dosing recommendation.
- Which peptide is better supported by science, FOXO4-DRI or Melanotan II?
- The highest available evidence level is "Animal model" for FOXO4-DRI and "Human trial" for Melanotan II. 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 Melanotan II in Germany and the United States?
- Germany: FOXO4-DRI — Research only, Melanotan II — Unapproved. United States: FOXO4-DRI — Research only, Melanotan II — Unapproved. These are factual summaries with source and review date on the individual pages.