Journal of Medicinal Chemistry,
Journal Year:
2019,
Volume and Issue:
62(16), P. 7575 - 7582
Published: July 22, 2019
A
focused
PROTAC
library
hijacking
cancer
therapeutic
target
CDK6
was
developed.
design
principle
as
"match/mismatch"
proposed
for
understanding
the
degradation
profile
differences
in
these
PROTACs.
Notably,
potent
PROTACs
with
specific
and
remarkable
potential
were
generated
by
linking
inhibitor
palbociclib
E3
ligase
CRBN
recruiter
pomalidomide.
The
strongly
inhibited
proliferation
of
hematopoietic
cells
including
multiple
myeloma
robustly
degraded
copy-amplified/mutated
forms
CDK6,
indicating
future
clinical
applications.
Molecular Cancer,
Journal Year:
2019,
Volume and Issue:
18(1)
Published: Oct. 16, 2019
Abstract
Background
YAP
activation
is
crucial
for
cancer
development
including
colorectal
(CRC).
Nevertheless,
it
remains
unclear
whether
N6-Methyladenosine
(m
6
A)
modified
transcripts
of
long
noncoding
RNAs
(lncRNAs)
can
regulate
in
progression.
We
investigated
the
functional
link
between
lncRNAs
and
m
A
modification
signaling
CRC
Methods
interacting
were
screened
by
RIP-sequencing,
RNA
FISH
immunofluorescence
co-staining
assays.
Interaction
lncRNA
GAS5
was
studied
biochemical
methods.
MeRIP-sequencing
combined
with
lncRNA-sequencing
used
to
identify
targets
YTHDF3
CRC.
Gain-of-function
Loss-of-function
analysis
performed
measure
function
GAS5-YAP-YTHDF3
axis
progression
vitro
vivo.
Results
directly
interacts
WW
domain
facilitate
translocation
endogenous
from
nucleus
cytoplasm
promotes
phosphorylation
subsequently
ubiquitin-mediated
degradation
inhibit
Notably,
we
demonstrate
reader
not
only
a
novel
target
but
also
key
player
facilitating
A-modified
degradation,
which
profile
new
insight
into
Clinically,
expressions
negatively
correlated
protein
levels
tumors
patients.
Conclusions
Our
study
uncovers
negative
loop
axis,
identifies
mechanism
A-induced
decay
on
may
offer
promising
approach
treatment.
Nature Communications,
Journal Year:
2021,
Volume and Issue:
12(1)
Published: March 19, 2021
The
majority
of
breast
cancers
express
the
estrogen
receptor
(ERα)
and
agents
targeting
this
pathway
represent
main
treatment
modality.
Endocrine
therapy
has
proven
successful
in
hormone-responsive
cancer
since
its
early
adoption
1940s
as
an
ablative
therapy.
Unfortunately,
therapeutic
resistance
arises,
leading
to
disease
recurrence
relapse.
Recent
studies
increased
our
understanding
how
changes
chromatin
landscape
deregulation
epigenetic
factors
orchestrate
resistant
phenotype.
Here,
we
will
discuss
epigenome
is
integral
determinant
hormone
response
why
are
promising
targets
for
overcoming
clinical
resistance.
Signal Transduction and Targeted Therapy,
Journal Year:
2022,
Volume and Issue:
7(1)
Published: Nov. 8, 2022
Abstract
As
an
evolutionarily
conserved
signalling
network,
the
Hippo
pathway
plays
a
crucial
role
in
regulation
of
numerous
biological
processes.
Thus,
substantial
efforts
have
been
made
to
understand
upstream
signals
that
influence
activity
pathway,
as
well
its
physiological
functions,
such
cell
proliferation
and
differentiation,
organ
growth,
embryogenesis,
tissue
regeneration/wound
healing.
However,
dysregulation
can
cause
variety
diseases,
including
cancer,
eye
cardiac
pulmonary
renal
hepatic
immune
dysfunction.
Therefore,
therapeutic
strategies
target
dysregulated
components
might
be
promising
approaches
for
treatment
wide
spectrum
diseases.
Here,
we
review
key
critical
functions
controlled
by
pathway.
Additionally,
diseases
associated
with
alterations
potential
therapies
targeting
will
discussed.
