Gastroenterology Research and Practice,
Journal Year:
2025,
Volume and Issue:
2025(1)
Published: Jan. 1, 2025
Objective:
Despite
N
6
‐methyladenosine
(m
A)
being
closely
involved
in
various
pathophysiological
processes,
its
potential
role
liver
injury
is
largely
unknown.
We
designed
the
current
research
to
study
of
fat
mass
and
obesity‐associated
protein
(FTO),
an
m
A
demethylase,
on
hepatic
ischemia‐reperfusion
(IRI).
Methods:
Wild‐type
mice
injected
with
adeno‐associated
virus
carrying
(AAV‐FTO)
or
green
fluorescent
(GFP)
(AAV‐GFP)
were
subjected
a
IRI
model
vivo.
Hematoxylin–eosin
staining
was
performed
observe
IRI.
Terminal
deoxynucleotidyl
transferase
dUTP
nick
end
labeling
(TUNEL)
used
cell
apoptosis.
Reverse
transcription
polymerase
chain
reaction
(RT‐PCR)
expression
FTO.
The
levels
FTO,
apoptosis,
autophagy‐associated
signaling
proteins
detected
by
western
blot.
Reactive
oxygen
species
(ROS)
determined
flow
cytometry,
immunohistochemistry
detect
FTO
LC3‐II
expression.
For
vitro
experiments,
cultured
hepatocytes
hypoxia/reoxygenation
(H/R)
stimulation.
Monodansylcadaverine
(MDC)
visualize
autophagic
vesicles.
Results:
In
present
study,
we
showed
that
IRI,
autophagy.
Specifically,
level
significantly
reduced
Besides,
increasing
ameliorated
animal
models,
accompanied
decreased
apoptosis
Furthermore,
inhibitor
(FB23‐2)
aggravated
autophagy
upon
H/R‐induced
damage.
Conclusion:
could
act
as
protective
effector
during
associated
FTO‐mediated
demethylation
modification
may
be
important
therapeutic
target
for
Chemical Society Reviews,
Journal Year:
2022,
Volume and Issue:
51(21), P. 8832 - 8876
Published: Jan. 1, 2022
ATTECs
and
several
other
emerging
degrader
technologies
hijacking
the
lysosomal
pathways
greatly
expand
spectrum
of
degradable
targets
provide
new
opportunities
for
targeted
drug
discovery.
Journal of Medicinal Chemistry,
Journal Year:
2024,
Volume and Issue:
67(10), P. 7668 - 7758
Published: May 7, 2024
Covalent
inhibitors
and
other
types
of
covalent
modalities
have
seen
a
revival
in
the
past
two
decades,
with
variety
new
targeted
drugs
having
been
approved
recent
years.
A
key
feature
such
molecules
is
an
intrinsically
reactive
group,
typically
weak
electrophile,
which
enables
irreversible
or
reversible
formation
bond
specific
amino
acid
target
protein.
This
often
called
"warhead",
critical
determinant
ligand's
activity,
selectivity,
general
biological
properties.
In
2019,
we
summarized
emerging
re-emerging
warhead
chemistries
to
cysteine
acids
(Gehringer,
M.;
Laufer,
S.
A.
J.
Med.
Chem.
62,
5673−5724;
DOI:
10.1021/acs.jmedchem.8b01153).
Since
then,
field
has
rapidly
evolved.
Here
discuss
progress
on
warheads
made
since
our
last
Perspective
their
application
medicinal
chemistry
chemical
biology.
Biochemistry,
Journal Year:
2022,
Volume and Issue:
62(3), P. 564 - 579
Published: Sept. 21, 2022
In
the
scope
of
targeted
protein
degradation
(TPD),
proteolysis-targeting
chimeras
(PROTACs),
leveraging
ubiquitin–proteasome
system,
have
been
extensively
studied.
However,
they
are
limited
to
soluble
and
membrane
proteins,
excluding
aggregated
extracellular
proteins
dysfunctional
organelles.
As
an
alternative
pathway,
lysosomes
serve
as
a
feasible
tool
for
accessing
these
untouched
and/or
organelles
by
proteosomes.
Here,
we
focus
on
reviewing
emerging
lysosome-mediated
TPD,
such
AUTAC,
ATTEC,
AUTOTAC,
LYTAC,
MoDE-A.
Intracellular
targets,
organelles,
can
be
degraded
via
autophagy–lysosome
pathway.
Extracellular
secreted
endosome–lysosome
addition,
summarize
mechanism
regulation
autophagy,
available
methods
assays
monitoring
autophagy
process,
recently
developed
chemical
probes
perturbing
pathways.
Nature Communications,
Journal Year:
2023,
Volume and Issue:
14(1)
Published: Nov. 30, 2023
Targeted
proteasomal
and
autophagic
protein
degradation,
often
employing
bifunctional
modalities,
is
a
new
paradigm
for
modulation
of
function.
In
an
attempt
to
explore
degradation
by
means
autophagy
we
combine
arylidene-indolinones
reported
bind
the
autophagy-related
LC3B-protein
ligands
PDEδ
lipoprotein
chaperone,
BRD2/3/4-bromodomain
containing
proteins
BTK-
BLK
kinases.
Unexpectedly,
resulting
degraders
do
not
induce
macroautophagy,
but
instead
direct
their
targets
ubiquitin-proteasome
system.
Target
mechanism
identification
reveal
that
covalently
DCAF11,
substrate
receptor
in
CUL4A/B-RBX1-DDB1-DCAF11
E3
ligase.
The
tempered
α,
β-unsaturated
indolinone
electrophiles
define
drug-like
DCAF11-ligand
class
enables
exploration
this
ligase
chemical
biology
medicinal
chemistry
programs.
arylidene-indolinone
scaffold
frequently
occurs
natural
products
which
raises
question
whether
ligand
classes
can
be
found
more
widely
among
related
compounds.
Phytomedicine,
Journal Year:
2024,
Volume and Issue:
132, P. 155791 - 155791
Published: May 29, 2024
Gastric
mucosal
injury
is
a
chronic
and
progressive
stomach
disease
that
can
be
caused
by
nonsteroidal
anti-inflammatory
drugs
(NSAIDs).
Therefore,
there
an
urgent
need
to
find
safe
effective
prevent
gastric
due
NSAIDs.
Cinnamaldehyde
(CA)
bioactive
compound
extracted
from
the
rhizome
of
cinnamon
has
various
pharmacological
functions,
including
anti-inflammatory,
analgesic,
antiapoptotic,
antioxidant
activities.
However,
potential
effect
CA
on
remains
unknown.
