Nucleic Acids Research,
Journal Year:
2020,
Volume and Issue:
48(15), P. e87 - e87
Published: June 5, 2020
Deoxyribonucleoside
triphosphates
(dNTPs)
are
vital
for
the
biosynthesis
and
repair
of
DNA.
Their
cellular
concentration
peaks
during
S
phase
cell
cycle.
In
non-proliferating
cells,
dNTP
concentrations
low,
making
their
reliable
quantification
from
tissue
samples
heterogeneous
composition
challenging.
Partly
because
this,
current
knowledge
related
to
regulation
disturbances
in
derive
mostly
culture
experiments
with
little
corroboration
at
or
organismal
level.
Here,
we
fill
methodological
gap
by
presenting
a
simple
non-radioactive
microplate
assay
dNTPs
minimum
requirement
4-12
mg
biopsy
material.
contrast
published
assays,
this
is
based
on
long
synthetic
single-stranded
DNA
templates
(50-200
nucleotides),
an
inhibitor-resistant
high-fidelity
polymerase,
double-stranded-DNA-binding
EvaGreen
dye.
The
quantified
reliably
less
than
50
fmol
each
four
discriminated
well
against
ribonucleotides.
Additionally,
thermostable
RNAse
HII-mediated
nicking
reaction
products
subsequent
shift
melting
temperature
allowed
near-complete
elimination
interfering
ribonucleotide
signal,
if
present.
Importantly,
measurement
minute
mouse
liver,
heart
skeletal
muscle.
Antioxidants and Redox Signaling,
Journal Year:
2018,
Volume and Issue:
30(8), P. 1062 - 1082
Published: Jan. 16, 2018
During
the
past
decades,
thiosemicarbazones
were
clinically
developed
for
a
variety
of
diseases,
including
tuberculosis,
viral
infections,
malaria,
and
cancer.
With
regard
to
malignant
class
α-N-heterocyclic
thiosemicarbazones,
here
especially
3-aminopyridine-2-carboxaldehyde
thiosemicarbazone
(Triapine),
was
intensively
in
multiple
clinical
phase
I/II
trials.
Recent
Advances:
Very
recently,
two
new
derivatives,
namely
COTI-2
di-2-pyridylketone
4-cyclohexyl-4-methyl-3-thiosemicarbazone
(DpC)
have
entered
I
evaluation.
Based
on
strong
metal-chelating/metal-interacting
properties
interference
with
cellular
iron
(and
copper)
homeostasis
is
assumed
play
an
important
role
their
biological
activity.In
this
review,
we
summarize
analyze
data
interaction
(α-N-heterocyclic)
iron,
special
aim
bridging
current
knowledge
mode
action
from
chemistry
(cell)
biology.
In
addition,
highlight
difference
classical
iron(III)
chelators
such
as
desferrioxamine
(DFO),
which
are
used
treatment
overload.We
want
emphasize
that
not
solely
removing
cells/organism.
contrast,
they
should
be
considered
iron-interacting
drugs
influencing
diverse
pathways
complex
multi-faceted
action.
Consequently,
addition
discussion
physicochemical
(e.g.,
stability,
redox
activity),
review
contains
overview
diversity
targets
drug
resistance
mechanisms.
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(2), P. 1263 - 1263
Published: Jan. 19, 2024
Replication
stress
(RS)
is
a
characteristic
state
of
cancer
cells
as
they
tend
to
exchange
precision
replication
for
fast
proliferation
and
increased
genomic
instability.
To
overcome
the
consequences
improper
control,
malignant
frequently
inactivate
parts
their
DNA
damage
response
(DDR)
pathways
(the
ATM-CHK2-p53
pathway),
while
relying
on
other
which
help
maintain
fork
stability
(ATR-CHK1).
This
creates
dependency
remaining
DDR
pathways,
vulnerability
further
destabilization
synthetic
lethality
inhibitors
with
common
oncogenic
alterations
such
mutations
TP53,
RB1,
ATM,
amplifications
MYC,
CCNE1
others.
The
RS
normally
limited
by
coordination
cell
cycle,
transcription
replication.
Inhibition
WEE1
PKMYT1
kinases,
prevent
unscheduled
mitosis
entry,
leads
fragility
under-replicated
sites.
Recent
evidence
also
shows
that
inhibition
Cyclin-dependent
kinases
(CDKs),
CDK4/6,
CDK2,
CDK8/19
CDK12/13
can
contribute
through
disruption
repair
control.
Here,
we
review
main
causes
in
cancers
well
therapeutic
targets—ATR,
CHK1,
PARP
inhibitors.
Biomolecules,
Journal Year:
2025,
Volume and Issue:
15(2), P. 168 - 168
Published: Jan. 23, 2025
The
DNA
damage
response
(DDR)
and
cellular
metabolism
exhibit
a
complex,
bidirectional
relationship
crucial
for
maintaining
genomic
integrity.
Studies
across
multiple
organisms,
from
yeast
to
humans,
have
revealed
how
cells
rewire
their
in
damage,
supporting
repair
processes
homeostasis.
We
discuss
immediate
metabolic
shifts
upon
detection
long-term
reprogramming
sustained
stability,
highlighting
key
signaling
pathways
participating
molecules.
Importantly,
we
examine
can
conversely
induce
changes
oxidative
stress
through
specific
mechanisms,
including
the
histone
H2A
variant
X
(H2AX)/ataxia
telangiectasia
mutated
(ATM)/NADPH
oxidase
1
(Nox1)
pathway
repair-specific
ROS
signatures.
review
covers
organelle-specific
responses
adaptations
associated
with
different
primary
focus
on
human
cells.
explore
implications
of
this
DDR–metabolism
crosstalk
cancer,
aging,
neurodegenerative
diseases,
emerging
therapeutic
opportunities.
By
integrating
recent
findings,
provides
comprehensive
overview
intricate
interplay
between
DDR
metabolism,
offering
new
perspectives
resilience
potential
avenues
intervention.
Mini-Reviews in Medicinal Chemistry,
Journal Year:
2019,
Volume and Issue:
20(8), P. 638 - 661
Published: Oct. 29, 2019
:
Thiosemicarbazones
(TSCs)
are
a
class
of
Schiff
bases
usually
obtained
by
the
condensation
thiosemicarbazide
with
suitable
aldehyde
or
ketone.
TSCs
have
been
focus
chemists
and
biologists
due
to
their
wide
range
pharmacological
effects.
One
promising
areas
in
which
these
excellent
metal
chelators
being
developed
is
use
against
cancer.
clinical
antitumor
spectrum
efficacy
various
tumor
types
such
as
leukemia,
pancreatic
cancer,
breast
non-small
cell
lung
cervical
prostate
cancer
bladder
To
obtain
better
activity,
different
series
modifying
heteroaromatic
system
molecules.
These
compounds
possessed
significant
antineoplastic
activity
when
carbonyl
attachment
side
chain
was
located
at
position
α
ring
nitrogen
atom,
whereas
β
γ
heterocyclic
N
atom
resulted
inactive
agents.
In
addition,
replacement
C
also
biologically
compound
suggesting
that
conjugated
N,N,S-tridentate
donor
set
essential
for
biological
activities
thiosemicarbazones.
Several
possible
mechanisms
implemented
anticancer
Cancer Research,
Journal Year:
2020,
Volume and Issue:
80(21), P. 4815 - 4827
Published: Sept. 9, 2020
Abstract
PIK3CA
encodes
the
p110α
catalytic
subunit
of
PI3K
and
is
frequently
mutated
in
human
cancers,
including
∼30%
colorectal
cancer.
Oncogenic
mutations
render
cancers
more
dependent
on
glutamine.
Here
we
report
that
glutaminase
inhibitor
CB-839
preferentially
inhibits
xenograft
growth
PIK3CA-mutant,
but
not
wild-type
(WT),
cancers.
Moreover,
combination
5-fluorouracil
(5-FU)
induces
PIK3CA-mutant
tumor
regression
models.
treatment
increased
reactive
oxygen
species
caused
nuclear
translocation
Nrf2,
which
turn
upregulated
mRNA
expression
uridine
phosphorylase
1
(UPP1).
UPP1
facilitated
conversion
5-FU
to
its
active
compound,
thereby
enhancing
inhibition
thymidylate
synthase.
Consistently,
knockout
abrogated
inhibitory
effect
combined
administration.
A
phase
I
clinical
trial
showed
capecitabine,
a
prodrug
5-FU,
was
well
tolerated
at
biologically-active
doses.
Although
designed
test
efficacy,
an
exploratory
analysis
data
trend
patients
with
cancer
might
derive
greater
benefit
from
this
strategy
as
compared
WT
These
results
effectively
demonstrate
targeting
glutamine
metabolism
may
be
effective
approach
for
treating
warrants
further
evaluation.
Significance:
Preclinical
suggest
capecitabine
could
serve
