Comparison
Exenatide vs. FOXO4-DRI
Two peptides side-by-side — identity, evidence base, legal status and known adverse events.
Identity
Category
Metabolic
Research other
CAS no.
141758-74-9
2074706-72-8
Molecular weight
4186.6 g/mol
3735 g/mol
Half-life
2.4 h
0.5 h
Sequence
HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPSD-Retro-Inverso-Variante eines FOXO4-Peptid-Fragments (LTLRKEPASEIAQSILEAYSQNGWANRRSGGKR — D-Aminosäuren in umgekehrter Sequenz)Mechanism of action
Exenatide
Exenatide is a 39-amino-acid peptide with about 53% sequence homology to human GLP-1. A glycine substitution at position 2 prevents dipeptidyl-peptidase-IV cleavage and extends the half-life from native GLP-1 (minutes) to about 2.4 hours. GLP-1 receptor activation glucose-dependently stimulates insulin secretion, inhibits glucagon and delays gastric emptying.
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
5
3
of which in humans
4
0
Effects recorded
3
3
Open conflicts
1
1
Documented adverse events
2
1