FOXO4-DRI
FOXO4 D-retro inverso peptide
Targeting senescent cells.
Half-life
~ extended (DRI resists proteases; hours)
Mol. weight
~ 5,382 g/mol (C234H380N76O68S2)
Sequence
D-retro-inverso modified FOXO4 fragment (D-amino acids, reverse order)
Discussions
0 threads
Overview
A D-retro-inverso (DRI) modified peptide designed to disrupt the interaction between FOXO4 and p53 in senescent cells, causing those cells to self-destruct (apoptosis). It is one of the most-discussed 'senolytic' research compounds — agents aimed at selectively clearing the senescent cells that accumulate with age and drive inflammation and tissue dysfunction.
Mechanism of action
In senescent cells, FOXO4 binds p53, preventing p53 from triggering apoptosis and thereby keeping the damaged-but-senescent cell alive. FOXO4-DRI is a D-retro-inverso peptide (built from D-amino acids in reversed order, making it protease-resistant) that competes for the FOXO4-p53 interaction, freeing p53 to induce apoptosis selectively in senescent cells. The DRI modification is key — it gives the peptide the stability to persist where a normal L-amino-acid peptide would be degraded. The goal is selective senescent-cell clearance (senolysis) without harming healthy cells.
Researched benefits
- Selective clearance of senescent cells (senolytic)
- DRI modification confers protease resistance
- Targets the FOXO4-p53 senescence-survival axis
Considerations
- Preclinical only; no human clinical data
- Senolysis is a frontier field with long-term safety unknowns
- Research context
Key Academic Literature & Studies
Search more in PubMedPeer-reviewed citations and clinical trials evaluating FOXO4-DRI in scientific literature.
Query PubMed for recent peer-reviewed preclinical and clinical publications on FOXO4-DRI:
View FOXO4-DRI index on PubMed (NCBI)