Comparison
Afamelanotide vs. FOXO4-DRI
Two peptides side-by-side — identity, evidence base, legal status and known adverse events.
Identity
Category
Research other
Research other
CAS no.
75921-69-6
2074706-72-8
Molecular weight
1646.87 g/mol
3735 g/mol
Half-life
12 h
0.5 h
Sequence
Ac-Ser-Tyr-Ser-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2D-Retro-Inverso-Variante eines FOXO4-Peptid-Fragments (LTLRKEPASEIAQSILEAYSQNGWANRRSGGKR — D-Aminosäuren in umgekehrter Sequenz)Mechanism of action
Afamelanotide
Afamelanotide is a synthetic analogue of α-melanocyte-stimulating hormone. It differs from native α-MSH by two substitutions — norleucine at position 4 and D-phenylalanine at position 7 — which make it metabolically more stable and more potent. As an agonist at the melanocortin-1 receptor (MC1R) on melanocytes, it activates adenylate cyclase, raises cAMP and increases tyrosinase activity via the transcription factor MITF. This shifts pigment synthesis toward eumelanin, which absorbs UV and visible light and has antioxidant properties — the presumed mechanism of photoprotection in EPP.
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.
Evidence base
Highest evidence
Human RCT
Animal model
Studies
4
3
of which in humans
4
0
Effects recorded
4
3
Open conflicts
1
1
Documented adverse events
4
1
Legal status
Full entries
Frequently asked questions
- What is the difference between Afamelanotide and FOXO4-DRI?
- Afamelanotide is classified as "Research other", while FOXO4-DRI is classified as "Research other". Afamelanotide: Afamelanotide (brand name Scenesse) is a synthetic 13-amino-acid analogue of α-melanocyte-stimulating hormone (α-MSH) and a melanocortin-1 receptor agonist. Unlike most peptides covered here, it is a regularly approved medicine: EMA approval in 2014/2015, FDA approval in 2019, in each case as a subcutaneous implant for the prevention of phototoxicity in adults with erythropoietic protoporphyria (EPP). It promotes eumelanin formation in the skin. 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. This page contrasts both neutrally and source-based — with no usage or dosing recommendation.
- Which peptide is better supported by science, Afamelanotide or FOXO4-DRI?
- The highest available evidence level is "Human RCT" for Afamelanotide and "Animal model" for FOXO4-DRI. 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 Afamelanotide and FOXO4-DRI in Germany and the United States?
- Germany: Afamelanotide — Prescription, FOXO4-DRI — Research only. United States: Afamelanotide — Prescription, FOXO4-DRI — Research only. These are factual summaries with source and review date on the individual pages.