Comparison
FOXO4-DRI vs. Semax
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
80714-61-0
Molecular weight
3735 g/mol
813.92 g/mol
Half-life
0.5 h
0.3 h
Sequence
D-Retro-Inverso-Variante eines FOXO4-Peptid-Fragments (LTLRKEPASEIAQSILEAYSQNGWANRRSGGKR — D-Aminosäuren in umgekehrter Sequenz)Met-Glu-His-Phe-Pro-Gly-ProMechanism 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.
Semax
Semax is a tetracosactide fragment analog without hormonal activity at MC2R. Proposed mechanisms include elevation of BDNF and NGF in hippocampus and striatum (in animal models), modulation of dopamine metabolism, and neuroprotective effects via anti-apoptotic pathways. A clear primary receptor is not established.
Evidence base
Highest evidence
Animal model
Human trial
Studies
3
4
of which in humans
0
2
Effects recorded
3
3
Open conflicts
1
1
Documented adverse events
1
1
Legal status
Full entries
Frequently asked questions
- What is the difference between FOXO4-DRI and Semax?
- FOXO4-DRI is classified as "Research other", while Semax 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. Semax: Synthetic heptapeptide derived from the N-terminal fragment of adrenocorticotropic hormone (ACTH 4-10). Approved in Russia for ischaemic stroke, cognitive function and ADHD in children. Western phase-3 trials absent. This page contrasts both neutrally and source-based — with no usage or dosing recommendation.
- Which peptide is better supported by science, FOXO4-DRI or Semax?
- The highest available evidence level is "Animal model" for FOXO4-DRI and "Human trial" for Semax. 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 Semax in Germany and the United States?
- Germany: FOXO4-DRI — Research only, Semax — Unapproved. United States: FOXO4-DRI — Research only, Semax — Unapproved. These are factual summaries with source and review date on the individual pages.