Comparison
FOXO4-DRI vs. Plecanatid
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
467426-54-6
Molecular weight
3735 g/mol
1682 g/mol
Half-life
0.5 h
no data
Sequence
D-Retro-Inverso-Variante eines FOXO4-Peptid-Fragments (LTLRKEPASEIAQSILEAYSQNGWANRRSGGKR — D-Aminosäuren in umgekehrter Sequenz)no data
Mechanism 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.
Plecanatid
Plecanatide is structurally analogous to the body's own uroguanylin and, like it, activates the GC-C receptor at the gut surface, raising cGMP and fluid secretion. Its pH-dependent activity shifts the effect toward the proximal small intestine.
Evidence base
Highest evidence
Animal model
Human RCT
Studies
3
0
of which in humans
0
0
Effects recorded
3
2
Open conflicts
1
1
Documented adverse events
1
1
Legal status
Full entries
Frequently asked questions
- What is the difference between FOXO4-DRI and Plecanatid?
- FOXO4-DRI is classified as "Research other", while Plecanatid 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. Plecanatid: Plecanatide is a 16-amino-acid analog of the body's own uroguanylin and a guanylate cyclase-C (GC-C) agonist. It is approved for chronic idiopathic constipation (CIC) and IBS with constipation (IBS-C). This page contrasts both neutrally and source-based — with no usage or dosing recommendation.
- Which peptide is better supported by science, FOXO4-DRI or Plecanatid?
- The highest available evidence level is "Animal model" for FOXO4-DRI and "Human RCT" for Plecanatid. 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 Plecanatid in Germany and the United States?
- Germany: FOXO4-DRI — Research only, Plecanatid — Unapproved. United States: FOXO4-DRI — Research only, Plecanatid — Prescription. These are factual summaries with source and review date on the individual pages.