Science Advances,
Journal Year:
2024,
Volume and Issue:
10(25)
Published: June 21, 2024
Autophagy-targeting
chimera
(AUTAC)
has
emerged
as
a
powerful
modality
that
can
selectively
degrade
tumor-related
pathogenic
proteins,
but
its
low
bioavailability
and
nonspecific
distribution
significantly
restrict
their
therapeutic
efficacy.
Inspired
by
the
guanine
structure
of
AUTAC
molecules,
we
here
report
supramolecular
artificial
Nano-AUTACs
(GM
NPs)
engineered
molecule
GN
[an
indoleamine
2,3-dioxygenase
(IDO)
degrader]
nucleoside
analog
methotrexate
(MTX)
through
interactions
for
tumor-specific
protein
degradation.
Their
nanostructures
allow
precise
localization
delivery
into
cancer
cells,
where
intracellular
acidic
environment
disrupt
to
release
MTX
eradicating
tumor
modulating
tumor-associated
macrophages,
activating
dendritic
inducing
autophagy.
Specifically,
induced
autophagy
facilitates
released
degrading
immunosuppressive
IDO
further
enhance
effector
T
cell
activity
inhibit
growth
metastasis.
This
study
offers
unique
strategy
building
nanoplatform
advance
field
in
immunotherapy.
Discover Oncology,
Journal Year:
2025,
Volume and Issue:
16(1)
Published: March 21, 2025
Ubiquitination
modifications
can
affect
hepatocellular
carcinoma
(HCC)
progression
through
various
signaling
pathways.
However,
no
significant
results
have
been
observed
regarding
protein
ubiquitination
in
HCC's
therapeutic
transformation.
This
study
aimed
to
explore
the
research
areas
related
and
HCC
from
a
bibliometric
perspective.
Articles
reviews
on
published
between
2000
2023
were
obtained
Web
of
Science
Core
Collection
(WOSCC).
CiteSpace,
VOSviewer,
R-bibliometrix
used
for
visualization
analyses.
Altogether,
358
papers
extracted
WOSCC.
Over
24
years,
number
publications
has
increased.
Since
beginning
2019,
studies
this
topic
increased
significantly,
indicating
that
role
modification
is
currently
popular.
China
leading
country
field
with
largest
publications.
The
Chinese
Academy
Sciences
one
most
influential
institutions.
Qiao,
Yongxia,
Zhang
Jie
are
highly
productive
authors
major
achievements.
journal
Cell
Death
&
Disease
had
highest
publications,
cited
was
Oncogene.
citation
burst
intensity
Sung
(2021).
In
keyword
strategy
map,
"cancer
antigens"
popular
keywords
research.
A
comprehensive
visual
analysis
conducted
using
methods,
showing
topics
over
past
two
decades,
thus
providing
references
future
direction
Journal of Medicinal Chemistry,
Journal Year:
2025,
Volume and Issue:
unknown
Published: April 17, 2025
Degraders
with
dual
activity
against
BRD4
and
CBP/EP300
were
designed.
A
structure-guided
design
approach
was
taken
to
assess
test
potential
exit
vectors
on
the
inhibitor,
ISOX-DUAL.
Candidate
degrader
panels
revealed
that
VHL-recruiting
moieties
could
mediate
dose-responsive
ubiquitination
of
BRD4.
panel
CRBN-recruiting
thalidomide-based
degraders
unable
induce
or
degradation
target
proteins.
High-resolution
protein
cocrystal
structures
an
unexpected
interaction
between
thalidomide
moiety
Trp81
first
bromodomain
The
inability
form
a
ternary
complex
provides
rationale
for
lack
these
compounds,
some
which
have
remarkable
affinities
close
those
(+)-JQ1,
as
low
65
nM
in
biochemical
assay,
vs
1.5
μM
their
POI
ligand,
Such
"degrader
collapse"
may
represent
under-reported
mechanism
by
putative
molecules
are
inactive
respect
degradation.
BMC Cancer,
Journal Year:
2024,
Volume and Issue:
24(1)
Published: April 22, 2024
Abstract
Background
Leptomeningeal
metastasis
(LM)
of
small
cell
lung
cancer
(SCLC)
is
a
highly
detrimental
occurrence
associated
with
severe
neurological
disorders,
lacking
effective
treatment
currently.
Proteolysis-targeting
chimeric
molecules
(PROTACs)
may
provide
new
therapeutic
avenues
for
podophyllotoxin
derivatives-resistant
SCLC
LM,
warranting
further
exploration.
Methods
The
line
H128
expressing
luciferase
were
mutated
by
MNNG
to
generate
H128-Mut
line.
After
subcutaneous
inoculation
into
nude
mice,
H128-LM
and
H128-BPM
(brain
parenchymal
metastasis)
lines
primarily
cultured
from
LM
BPM
tissues
individually,
employed
in
vitro
drug
testing.
SCLC-LM
mouse
model
was
established
inoculating
mice
via
carotid
artery
subjected
vivo
RNA-seq
immunoblotting
conducted
uncover
the
molecular
targets
LM.
Results
successfully
established,
confirmed
live
imaging
histological
examination.
upregulated
genes
included
EZH2,
SLC44A4,
VEGFA,
etc.
both
cells,
while
SLC44A4
particularly
cells.
When
combined
PROTAC
EZH2
degrader-1,
sensitivity
cisplatin,
etoposide
(VP16),
teniposide
(VM26)
significantly
increased
vitro.
trials
demonstrated
that
degrader-1
plus
VM26
or
cisplatin/
VP16
inhibited
tumour
compared
alone
(
P
<
0.01).
Conclusion
effectively
simulates
pathophysiological
process
leptomeninges.
overcomes
chemoresistance
SCLC,
suggesting
its
potential
value
Science Advances,
Journal Year:
2024,
Volume and Issue:
10(25)
Published: June 21, 2024
Autophagy-targeting
chimera
(AUTAC)
has
emerged
as
a
powerful
modality
that
can
selectively
degrade
tumor-related
pathogenic
proteins,
but
its
low
bioavailability
and
nonspecific
distribution
significantly
restrict
their
therapeutic
efficacy.
Inspired
by
the
guanine
structure
of
AUTAC
molecules,
we
here
report
supramolecular
artificial
Nano-AUTACs
(GM
NPs)
engineered
molecule
GN
[an
indoleamine
2,3-dioxygenase
(IDO)
degrader]
nucleoside
analog
methotrexate
(MTX)
through
interactions
for
tumor-specific
protein
degradation.
Their
nanostructures
allow
precise
localization
delivery
into
cancer
cells,
where
intracellular
acidic
environment
disrupt
to
release
MTX
eradicating
tumor
modulating
tumor-associated
macrophages,
activating
dendritic
inducing
autophagy.
Specifically,
induced
autophagy
facilitates
released
degrading
immunosuppressive
IDO
further
enhance
effector
T
cell
activity
inhibit
growth
metastasis.
This
study
offers
unique
strategy
building
nanoplatform
advance
field
in
immunotherapy.
