FOXO4-DRI

Longevity

aka Proxofim · FOXO4 D-retro inverso peptide · FOXO4-p53 interaction antagonist

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Formula

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MW (Da)

Half-life

hours (preclinical)

Saves

Overview

FOXO4-DRI is a designed D-retro-inverso peptide built from the FOXO4 interaction surface and engineered to disrupt the FOXO4–p53 axis specifically in senescent cells. It is a research-stage senolytic with no human clinical trials in the retrieved literature.

Mechanism

The central mechanism is consistent across papers. FOXO4-DRI competes with FOXO4 for p53 binding, disrupts the FOXO4–p53 complex, and promotes p53 nuclear exclusion followed by apoptosis in senescent cells. Structural work has reinforced that the disordered p53 transactivation domain is a relevant target. Newer mechanistic studies in endothelial senescence and keloid fibroblasts continue to support the same senolytic logic.

Reported benefits

0

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Senolytic activity in cell and orthotopic mouse cancer models

In cell culture and orthotopic mouse cancer models, FOXO4-derived peptides showed senolytic activity against senescent human cancer cells.

[foxo4-pmc-cancer-models]

preclinical

Selective senescent-cell removal in expanded human chondrocytes

In expanded human chondrocytes, FOXO4-DRI selectively removed senescent cells and improved chondrogenic potential.

[foxo4-pmc-mechanism]

preclinical

Improved testicular microenvironment in naturally aged mice

In naturally aged mice, FOXO4-DRI improved the testicular microenvironment and alleviated age-related testosterone insufficiency.

[foxo4-pmc-mechanism]

preclinical

Reported side effects

No human safety data
anecdotal
The accessible preclinical literature focuses on intended senolytic apoptosis in senescent cells, not on a formal translational safety package. Incidence, severity, and safety margins in humans are unspecified.
Selectivity for senescent vs healthy cells still being established
preclinical
Mechanistically the peptide triggers cell-death pathways. Demonstrating selectivity for senescent cells over healthy cells in humans is a key open question.

Dosing notes

Dosing is model-dependent in preclinical work. Accessible abstracts do not provide a reliable standardized dose table for cross-study comparison. Human dose, route, and frequency are unspecified because no human trial evidence was retrieved.

Research use only. Information on this page is editorial reference, not medical or dosing advice. Always consult qualified medical guidance before use.

Storage

Peer-reviewed stability data were not identified. Standard synthetic-peptide supplier guidance would favor lyophilized cold storage and freeze-thaw minimization; that remains generic peptide handling guidance, not FOXO4-DRI-specific validated stability data.

Vendors carrying FOXO4-DRI

No approved vendors are listing this peptide yet. Check back later or browse the full vendor directory.

Discussion

Ask, answer, and vote on questions about FOXO4-DRI.

1
Posted by@admin·May 19, 2026·0 comments
Test question does this work?
-1
Posted by@admin·May 19, 2026·2 comments
Test test test
- -1
  @admin·May 19, 2026
  test test test
  1
  @admin·May 19, 2026
  Test test test test test test test test test test test test
-1
Posted by@admin·May 19, 2026·0 comments
test 2 teest t2

References

[foxo4-pmc-senolytic-review]
FOXO4-DRI senolytic peptide overview
Review authors per PMC entry · PubMed Central
Source
[foxo4-pmc-cancer-models]
Senolytic activity of FOXO4-derived peptides in cancer and aged tissue models
Study authors per PMC entry · PubMed Central
Source
[foxo4-pmc-mechanism]
FOXO4-DRI mechanism, selectivity, and preclinical activity
Study authors per PMC entry · PubMed Central
Source

Senolytic activity in cell and orthotopic mouse cancer models

Selective senescent-cell removal in expanded human chondrocytes

Improved testicular microenvironment in naturally aged mice

No human safety data

Selectivity for senescent vs healthy cells still being established

Discussion