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FOXO4DRI

FOXO4-DRI is a synthetic peptide designed to interfere with the interaction between the transcription factor FOXO4 and the tumor suppressor p53. The DRI in the name stands for D-retro-inverse, a peptide design intended to enhance stability and cell permeability. It is studied as a senolytic agent, aiming to selectively eliminate senescent cells to alleviate aging-related dysfunction.

Mechanism: In many senescent cells, FOXO4 binds p53 in the nucleus to help maintain cell cycle arrest.

Research status: FOXO4-DRI has been investigated mainly in cell culture and animal studies. In aged mouse models,

Delivery and design: The peptide is designed to be cell-permeant and is stabilized by its DRI configuration,

Clinical status: FOXO4-DRI is not approved for clinical use. It remains a research tool and potential therapeutic

FOXO4-DRI
binds
to
FOXO4
and
disrupts
its
interaction
with
p53,
causing
p53
to
relocate
to
the
cytoplasm
and
promoting
apoptosis
of
the
senescent
cell.
This
disruption
of
the
FOXO4–p53
signaling
axis
underpins
its
purported
senolytic
activity
in
preclinical
models.
treatment
with
FOXO4-DRI
reduced
markers
of
senescence
and
was
associated
with
improvements
in
certain
age-related
phenotypes
and
tissue
function
in
some
experiments.
There
is
no
clinical
evidence
in
humans,
and
the
approach
remains
experimental.
which
supports
systemic
delivery
in
preclinical
work.
As
with
other
senolytics,
questions
about
long-term
safety,
dosing,
and
the
consistency
of
effects
across
tissues
are
active
areas
of
research.
candidate,
with
ongoing
work
to
assess
safety,
efficacy,
and
applicability
to
aging-related
diseases.