Comparison
FOXO4-DRI vs. Tirzepatide
Two peptides side-by-side — identity, evidence base, legal status and known adverse events.
Identity
Category
Research other
Metabolic
CAS no.
2074706-72-8
2023788-19-2
Molecular weight
3735 g/mol
4813 g/mol
Half-life
0.5 h
116 h
Sequence
D-Retro-Inverso-Variante eines FOXO4-Peptid-Fragments (LTLRKEPASEIAQSILEAYSQNGWANRRSGGKR — D-Aminosäuren in umgekehrter Sequenz)YXEGTFTSDYSIYLDKIAQKAFVQWLIAGGPSSGAPPPSMechanism 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.
Tirzepatide
Tirzepatide is a 39-amino-acid peptide acting as a dual agonist at the GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide) receptors. Activation of both incretin receptors via G-protein-coupled signalling raises insulin secretion in a glucose-dependent manner, lowers glucagon secretion and delays gastric emptying. Centrally, satiety perception is modulated. A fatty-acid side chain binds to serum albumin and extends the half-life to about five days.
Evidence base
Highest evidence
Animal model
Human RCT
Studies
3
3
of which in humans
0
3
Effects recorded
3
4
Open conflicts
1
0
Documented adverse events
1
2