Expert Opinion on Drug Discovery,
Год журнала:
2023,
Номер
19(2), С. 147 - 159
Опубликована: Ноя. 7, 2023
Introduction
Escalating
costs
and
inherent
uncertainties
associated
with
drug
discovery
invite
initiatives
to
improve
its
efficiency
de-risk
campaigns
for
inventing
better
therapeutics.
One
such
initiative
involves
recognizing
exploiting
current
approaches
in
therapeutics
invention
molecular
mechanisms
of
action
that
hold
promise
designing
targeting
new
chemical
entities
as
drugs.
Biomedicine & Pharmacotherapy,
Год журнала:
2023,
Номер
163, С. 114710 - 114710
Опубликована: Май 3, 2023
α-Mangostin
(α-MG)
is
a
natural
xanthone
obtained
from
the
pericarps
of
mangosteen.
It
exhibits
excellent
potential,
including
anti-cancer,
neuroprotective,
antimicrobial,
antioxidant,
and
anti-inflammatory
properties,
induces
apoptosis.
α-MG
controls
cell
proliferation
by
modulating
signaling
molecules,
thus
implicated
in
cancer
therapy.
possesses
incredible
pharmacological
features
modulates
crucial
cellular
molecular
factors.
Due
to
its
lesser
water
solubility
pitiable
target
selectivity,
has
limited
clinical
application.
As
known
gained
significant
attention
scientific
community,
increasing
interest
extensive
technical
biomedical
applications.
Nanoparticle-based
drug
delivery
systems
were
designed
improve
efficiency
α-MG.
This
review
focused
on
recent
developments
therapeutic
potential
managing
neurological
diseases,
with
special
focus
mechanism
action.
In
addition,
we
highlighted
biochemical
features,
metabolism,
functions,
anti-inflammatory,
antioxidant
effects
pre-clinical
applications
Pharmaceuticals,
Год журнала:
2023,
Номер
16(9), С. 1283 - 1283
Опубликована: Сен. 11, 2023
The
processes
used
by
academic
and
industrial
scientists
to
discover
new
drugs
have
recently
experienced
a
true
renaissance,
with
many
exciting
techniques
being
developed
over
the
past
5-10
years
alone.
Drug
design
discovery,
search
for
safe
well-tolerated
compounds,
as
well
ineffectiveness
of
existing
therapies,
society's
insufficient
knowledge
concerning
prophylactics
pharmacotherapy
most
common
diseases
today,
comprise
serious
challenge.
This
can
influence
not
only
quality
human
life,
but
also
health
whole
societies,
which
became
evident
during
COVID-19
pandemic.
In
general,
process
drug
development
consists
three
main
stages:
preclinical
using
cell-based
animal
models/tests,
clinical
trials
on
humans
and,
finally,
forward
moving
toward
step
obtaining
regulatory
approval,
in
order
market
potential
drug.
this
review,
we
will
attempt
outline
first
important
consecutive
phases
development,
based
experience
cooperating
complementary
centers
Visegrád
group;
i.e.,
Medical
University
Lublin,
Poland,
Masaryk
Brno,
Czech
Republic,
Comenius
Bratislava,
Slovak
Republic.
Biomarker Research,
Год журнала:
2024,
Номер
12(1)
Опубликована: Ноя. 19, 2024
Abstract
Epilepsy
remains
a
prevalent
chronic
neurological
disease
that
is
featured
by
aberrant,
recurrent
and
hypersynchronous
discharge
of
neurons
poses
great
challenge
to
healthcare
systems.
Although
several
therapeutic
interventions
are
successfully
utilized
for
treating
epilepsy,
they
can
merely
provide
symptom
relief
but
cannot
exert
disease-modifying
effect.
Therefore,
it
urgent
need
explore
other
potential
mechanism
develop
novel
approach
delay
the
epileptic
progression.
Since
approximately
30
years
ago,
histone
deacetylases
(HDACs),
versatile
epigenetic
regulators
responsible
gene
transcription
via
binding
histones
or
non-histone
substrates,
have
grabbed
considerable
attention
in
drug
discovery.
There
also
substantial
evidences
supporting
aberrant
expressions
and/activities
HDAC
isoforms
reported
epilepsy
inhibitors
(HDACi)
been
purposes
this
condition.
However,
specific
mechanisms
underlying
role
HDACs
progression
not
fully
understood.
Herein,
we
reviewed
basic
information
HDACs,
summarized
recent
findings
associated
with
roles
diverse
subunits
discussed
regulatory
which
affected
development
epilepsy.
Additionally,
provided
brief
discussion
on
as
promising
targets
treatment,
serving
valuable
reference
study
clinical
translation
field.
Molecular Aspects of Medicine,
Год журнала:
2022,
Номер
88, С. 101157 - 101157
Опубликована: Ноя. 29, 2022
Vision
impairment
has
devastating
consequences
for
the
quality
of
human
life.
The
cells
and
tissues
associated
with
visual
process
must
function
throughout
one's
life
span
maintain
homeostasis
despite
exposure
to
a
variety
insults.
Maintenance
proteome
is
termed
proteostasis,
vital
normal
cellular
functions,
especially
at
an
advanced
age.
Here
we
describe
basic
aspects
from
protein
synthesis
folding
degradation,
discuss
current
status
field
particular
focus
on
major
age-related
eye
diseases:
macular
degeneration,
cataract,
glaucoma.
Our
intent
allow
vision
scientists
determine
where
how
harness
proteostatic
machinery
extending
functional
in
aging
retina,
lens,
trabecular
meshwork.
Several
common
themes
have
emerged
these
having
vastly
different
metabolisms.
Continued
insults,
including
chronic
stress
advancing
age,
increases
burden
reduces
fidelity
degradation
machineries
ubiquitin-proteasome
autophagy-lysosome
systems
that
recognize
remove
damaged
proteins.
This
"double
jeopardy"
results
exponential
accumulation
cytotoxic
proteins
We
conclude
discussion
challenges
maintaining
appropriate
balance
pathways,
suggest
harnessing
capacities
should
provide
new
opportunities
design
interventions
attenuating
diseases
before
they
limit
sight.
Molecules,
Год журнала:
2023,
Номер
28(9), С. 3698 - 3698
Опубликована: Апрель 25, 2023
Cancer
treatments
with
targeted
therapy
have
gained
immense
interest
due
to
their
low
levels
of
toxicity
and
high
selectivity.
Proteolysis-Targeting
Chimeras
(PROTACs)
drawn
special
attention
in
the
development
cancer
therapeutics
owing
unique
mechanism
action,
ability
target
undruggable
proteins,
focused
engagement.
PROTACs
selectively
degrade
protein
through
ubiquitin-proteasome
system,
which
describes
a
different
mode
action
compared
conventional
small-molecule
inhibitors
or
even
antibodies.
Among
types,
prostate
(PC)
is
most
prevalent
non-cutaneous
men.
Genetic
alterations
overexpression
several
genes,
such
as
FOXA1,
AR,
PTEN,
RB1,
TP53,
etc.,
suppress
immune
response,
resulting
drug
resistance
drugs
cancer.
Since
progression
ARV-110
(PROTAC
for
PC)
into
clinical
phases,
focus
research
has
quickly
shifted
degraders
targeting
The
present
review
highlights
an
overview
superiority
over
inhibitors.
We
also
delve
underlying
pathophysiology
disease
explain
structural
design
linkerology
strategies
PROTAC
molecules.
Additionally,
we
touch
on
various
targets
cancer,
including
androgen
receptor
(AR)
other
critical
oncoproteins,
discuss
future
prospects
challenges
this
field.
Medicinal Research Reviews,
Год журнала:
2023,
Номер
43(5), С. 1748 - 1777
Опубликована: Апрель 29, 2023
Abstract
Parkinson's
disease
(PD)
is
a
multifactorial
due
to
complex
interplay
between
genetic
and
epigenetic
factors.
Recent
efforts
shed
new
light
on
the
mechanisms
involved
in
regulating
pathways
related
development
of
PD,
including
DNA
methylation,
posttranslational
modifications
histones,
presence
microRNA
(miRNA
or
miR).
Epigenetic
regulators
are
potential
therapeutic
targets
for
neurodegenerative
disorders.
In
review,
we
aim
summarize
regulation
describe
how
methyltransferases,
histone
deacetylases,
acetyltransferases
that
mediate
key
processes
PD
attractive
targets.
We
discuss
use
inhibitors
and/or
activators
these
models
patients,
small
molecule
modulators
elicit
neuroprotective
effects.
Further
more,
given
importance
miRNAs
their
contributions
underlying
will
be
discussed
as
well,
together
with
miRNA‐based
therapies.
Brain Sciences,
Год журнала:
2022,
Номер
12(5), С. 672 - 672
Опубликована: Май 21, 2022
Parkinson’s
disease
(PD)
is
a
chronic
progressive
neurodegenerative
that
increasingly
becoming
global
threat
to
the
health
and
life
of
elderly
worldwide.
Although
there
are
some
drugs
clinically
available
for
treating
PD,
these
treatments
can
only
alleviate
symptoms
PD
patients
but
cannot
completely
cure
disease.
Therefore,
exploring
other
potential
mechanisms
develop
more
effective
modify
course
still
highly
desirable.
Over
last
two
decades,
histone
deacetylases,
as
an
important
group
epigenetic
targets,
have
attracted
much
attention
in
drug
discovery.
This
review
focused
on
current
knowledge
about
deacetylases
involved
pathophysiology
their
inhibitors
used
studies.
Further
perspectives
related
small
molecules
inhibit
or
degrade
treat
were
also
discussed.
