Vergelijking
FOXO4-DRI vs. MOTS-c
Twee peptiden naast elkaar — identiteit, bewijsbasis, juridische status en bekende bijwerkingen.
Identiteit
Categorie
Onderzoek (overig)
Onderzoek (overig)
CAS-nr.
2074706-72-8
1627580-64-6
Molecuulmassa
3735 g/mol
2174.61 g/mol
Halfwaardetijd
0.5 h
geen gegevens
Sequentie
D-Retro-Inverso-Variante eines FOXO4-Peptid-Fragments (LTLRKEPASEIAQSILEAYSQNGWANRRSGGKR — D-Aminosäuren in umgekehrter Sequenz)Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-ArgWerkingsmechanisme
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.
MOTS-c
MOTS-c arises from a short open reading frame located in the 12S rRNA region of the mitochondrial genome — unlike most peptides it is therefore not encoded by nuclear DNA. Mechanistically, preclinical work describes MOTS-c as modulating the folate cycle and the de novo purine biosynthesis tethered to it, thereby affecting the AMP/ATP ratio and, downstream, AMP-activated protein kinase (AMPK). Under metabolic stress, an AMPK-dependent translocation of the peptide into the cell nucleus and involvement in the regulation of stress-responsive genes (including via antioxidant-response-element-regulated transcription factors) have also been reported. These models derive predominantly from cell culture and rodents; the extent to which they reflect human physiology after administration of exogenous synthetic MOTS-c is not established by human studies.
Bewijsbasis
Hoogste bewijs
Diermodel
Humane studie
Studies
3
4
waarvan bij mensen
0
1
Geregistreerde effecten
3
4
Openstaande tegenstrijdigheden
1
1
Gedocumenteerde bijwerkingen
1
1
Juridische status
Volledige vermeldingen
Frequently asked questions
- What is the difference between FOXO4-DRI and MOTS-c?
- FOXO4-DRI is classified as "Onderzoek (overig)", while MOTS-c is classified as "Onderzoek (overig)". 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. MOTS-c: MOTS-c is a 16-amino-acid mitochondrial-encoded peptide (mitochondrial-derived peptide, MDP) whose open reading frame lies within the 12S rRNA region of mitochondrial DNA. In basic research (including the laboratories of Changhan Lee and Pinchas Cohen) it is described as a regulator of metabolic homeostasis and an activator of the AMPK pathway, and is sometimes discussed as an 'exercise mimetic'. The evidence comes almost entirely from cell and animal models; controlled human trials of MOTS-c as a therapeutic are lacking. It is not approved as a medicine anywhere and is traded on the grey market as a research chemical. This page contrasts both neutrally and source-based — with no usage or dosing recommendation.
- Which peptide is better supported by science, FOXO4-DRI or MOTS-c?
- The highest available evidence level is "Diermodel" for FOXO4-DRI and "Humane studie" for MOTS-c. 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 MOTS-c in Germany and the United States?
- Duitsland: FOXO4-DRI — Alleen onderzoek, MOTS-c — Niet goedgekeurd. Verenigde Staten: FOXO4-DRI — Alleen onderzoek, MOTS-c — Niet goedgekeurd. These are factual summaries with source and review date on the individual pages.