Enzalutamide
is
a
drug
used
to
treat
PC.
Docetaxel
for
chemotherapy
different
cancers
including
prostate
cancer
(PC).
The
effectiveness
of
these
drugs
in
treating
castration-resistant
(CRPC)
not
consistent
and
thus,
CRPC
still
an
incurable
disease.
Recent
evidence
showed
that
the
bio-inhibitor
FABP5,
dmrFABP5,
suppressed
tumorigenicity
metastasis
cells.
In
this
work,
we
studied
possible
synergic
effect
dmrFABP5
combined
with
either
or
on
suppressing
PC
A
highly
significant
was
observed
when
combination
androgen-responsive
cells
22RV1.
also
22RV1
malignant,
androgen-receptor
(AR)-negative
DU145
These
applications
exhibited
inhibitory
action
viability,
migration,
invasion
colony
formation
abilities
both
22RV1and
However,
did
produce
any
suppression
FABP5-negative
cell
line
LNCaP,
although
can
significantly
suppress
LNCaP
as
single
agent.
Further
investigations
suggested
synergistic
effects
were
produced
by
interrupting
FABP5-related
signal
transduction
pathway
Journal of Medicinal Chemistry,
Journal Year:
2023,
Volume and Issue:
66(14), P. 9894 - 9915
Published: July 10, 2023
Aldo-keto
reductase
1C3
(AKR1C3)
is
overexpressed
in
castration-resistant
prostate
cancer
where
it
acts
to
drive
proliferation
and
aggressiveness
by
producing
androgens.
The
reductive
action
of
the
enzyme
leads
chemoresistance
development
against
various
clinical
antineoplastics
across
a
range
cancers.
Herein,
we
report
continued
optimization
selective
AKR1C3
inhibitors
identification
5r,
potent
inhibitor
(IC50
=
51
nM)
with
>1216-fold
selectivity
for
over
closely
related
isoforms.
Due
cognizance
poor
pharmacokinetics
associated
free
carboxylic
acids,
methyl
ester
prodrug
strategy
was
pursued.
4r
converted
acid
5r
vitro
mouse
plasma
vivo.
vivo
pharmacokinetic
evaluation
revealed
an
increase
systemic
exposure
increased
maximum
concentration
compared
direct
administration
acid.
demonstrated
dose-dependent
effect
reduce
tumor
volume
22Rv1
xenografts
without
observed
toxicity.
Cancer Treatment and Research Communications,
Journal Year:
2023,
Volume and Issue:
35, P. 100685 - 100685
Published: Jan. 1, 2023
A
recent
phase
Ib
study
investigating
the
use
of
reformulated
niclosamide
in
combination
with
abiraterone
and
prednisone
patients
castration-resistant
prostate
cancer
(CRPC)
demonstrated
encouraging
preliminary
efficacy
low
toxicity.
Preclinical
studies
have
reported
that
at
clinically
relevant
concentrations
inhibits
androgen
receptor
splice
variant
7
(AR-V7),
a
known
tumor
driver
CRPC.
However,
magnitude
anti-tumor
effects
either
used
alone
or
these
experimental
models,
far
exceeded
what
could
been
explained
as
simple
AR-V7
inhibition.
Niclosamide
also
acts
an
oxidative
phosphorylation
(OxPhos)
uncoupler
mitochondria.
This
raises
question
whether
observed
were
partly
mediated
by
OxPhos
Most
inhibitors
did
not
demonstrate
selectivity
towards
cells
failed
to
enter
clinical
practice
due
unacceptable
some
mitochondrial
uncouplers
greater
cytotoxicity
against
cancerous
compared
non-cancerous.
Hyperpolarization
cell
mitochondria,
more
alkaline
matrix
be
potential
reasons
for
this.
can
alter
Wnt/β-catenin,
mTOR,
Notch,
NF-kB
STAT3
signaling
pathways.
Hence,
mechanism
action
CRPC
requires
further
investigation.
will
potentially
lead
new
opportunities
develop
investigate
even
selective
effective
treatments
cancer.
Enzalutamide
is
a
drug
used
to
treat
PC.
Docetaxel
for
chemotherapy
different
cancers
including
prostate
cancer
(PC).
The
effectiveness
of
these
drugs
in
treating
castration-resistant
(CRPC)
not
consistent
and
thus,
CRPC
still
an
incurable
disease.
Recent
evidence
showed
that
the
bio-inhibitor
FABP5,
dmrFABP5,
suppressed
tumorigenicity
metastasis
cells.
In
this
work,
we
studied
possible
synergic
effect
dmrFABP5
combined
with
either
or
on
suppressing
PC
A
highly
significant
was
observed
when
combination
androgen-responsive
cells
22RV1.
also
22RV1
malignant,
androgen-receptor
(AR)-negative
DU145
These
applications
exhibited
inhibitory
action
viability,
migration,
invasion
colony
formation
abilities
both
22RV1and
However,
did
produce
any
suppression
FABP5-negative
cell
line
LNCaP,
although
can
significantly
suppress
LNCaP
as
single
agent.
Further
investigations
suggested
synergistic
effects
were
produced
by
interrupting
FABP5-related
signal
transduction
pathway
