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.
Expert Opinion on Drug Discovery,
Год журнала:
2024,
Номер
19(4), С. 451 - 470
Опубликована: Март 8, 2024
Introduction
The
current
drug
discovery
paradigm
of
'one
drug,
multiple
targets'
has
gained
attention
from
both
the
academic
medicinal
chemistry
community
and
pharmaceutical
industry.
This
is
in
response
to
urgent
need
for
effective
agents
treat
multifactorial
chronic
diseases.
molecular
hybridization
strategy
a
useful
tool
that
been
widely
explored,
particularly
last
two
decades,
design
multi-target
drugs.
Nanoscale,
Год журнала:
2024,
Номер
16(9), С. 4378 - 4391
Опубликована: Янв. 1, 2024
Schematic
illustration
of
the
combinational
strategy
nanotechnology
and
PROTACs
(Nano-PROTACs):
typical
shortcomings
traditional
nanotechnology-based
strategies
for
PROTAC
drugs
optimization.
Journal of Translational Medicine,
Год журнала:
2025,
Номер
23(1)
Опубликована: Фев. 4, 2025
Abstract
The
revolutionary
CRISPR-Cas9
system
leverages
a
programmable
guide
RNA
(gRNA)
and
Cas9
proteins
to
precisely
cleave
problematic
regions
within
DNA
sequences.
This
groundbreaking
technology
holds
immense
potential
for
the
development
of
targeted
therapies
wide
range
diseases,
including
cancers,
genetic
disorders,
hereditary
diseases.
based
genome
editing
is
multi-step
process
such
as
designing
precise
gRNA,
selecting
appropriate
Cas
protein,
thoroughly
evaluating
both
on-target
off-target
activity
Cas9-gRNA
complex.
To
ensure
accuracy
effectiveness
system,
after
cleavage,
requires
careful
analysis
resultant
outcomes
indels
deletions.
Following
success
artificial
intelligence
(AI)
in
various
fields,
researchers
are
now
leveraging
AI
algorithms
catalyze
optimize
system.
achieve
this
goal
AI-driven
applications
being
integrated
into
each
step,
but
existing
predictors
have
limited
performance
many
steps
still
rely
on
expensive
time-consuming
wet-lab
experiments.
primary
reason
behind
low
gap
between
CRISPR
fields.
Effective
integration
demands
comprehensive
knowledge
domains.
paper
bridges
research.
It
offers
unique
platform
grasp
deep
understanding
biological
foundations
step
process.
Furthermore,
it
provides
details
80
available
system-related
datasets
that
can
be
utilized
develop
applications.
Within
landscape
process,
insights
representation
learning
methods,
machine
methods
trends,
values
50
predictive
pipelines.
In
context
classifiers/regressors,
thorough
pipelines
recommendations
more
robust
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.
Journal of Medicinal Chemistry,
Год журнала:
2023,
Номер
66(3), С. 1700 - 1711
Опубликована: Янв. 30, 2023
Targeted
protein
degradation
(TPD)
technology
is
based
on
a
unique
pharmacological
mechanism
that
has
profoundly
revolutionized
medicinal
research
by
overcoming
limitations
associated
with
traditional
small-molecule
drugs.
Autophagy,
for
intracellular
waste
disposal
and
recovery,
an
important
biological
process
in
research.
Recently,
studies
have
demonstrated
several
emerging
autophagic
degraders
can
treat
human
diseases.
Herein
we
summarize
the
progress
degraders,
including
autophagosome-tethering
compounds
(ATTEC),
autophagy-targeting
chimeras
(AUTAC),
AUTOphagy-TArgeting
(AUTOTAC),
treating
These
exhibit
excellent
potential
neurodegenerative
Our
provides
new
avenue
TPD
via
autophagy.
Signal Transduction and Targeted Therapy,
Год журнала:
2024,
Номер
9(1)
Опубликована: Окт. 18, 2024
PROteolysis
TArgeting
Chimeras
(PROTACs)
have
been
considered
the
next
blockbuster
therapies.
However,
due
to
their
inherent
limitations,
efficacy
of
PROTACs
is
frequently
impaired
by
limited
tissue
penetration
and
particularly
insufficient
cellular
internalization
into
action
sites.
Herein,
based
on
ultra-pH-sensitive
enzyme-sensitive
nanotechnology,
a
type
polymer
PROTAC
conjugated
pH/cathepsin
B
sequential
responsive
nanoparticles
(PSRNs)
are
deliberately
designed,
following
construction
for
Cyclin-dependent
kinase
4
6
(CDK4/6).
Colorectal
cancer
(CRC)
which
hardly
responds
many
treatments
even
immune
checkpoint
blockades
was
selected
as
tumor
model
in
this
study.
As
result,
PSRNs
were
found
maintain
nanostructure
(40
nm)
circulation
efficiently
accumulated
tumors
via
enhanced
permeation
retention
effect.
Then,
they
dissociated
unimers
(<10
response
an
acidic
microenvironment,
facilitating
internalization.
Eventually,
CDK4/6
degrading
released
intracellularly
cleavage
cathepsin
B.
Importantly,
led
degradation
target
protein
vitro
vivo.
The
also
augmented
blockades,
through
upregulation
programmed
cell
death-ligand
1
(PD-L1)
expression
cells
suppression
regulatory
T
proliferation
microenvironment.
By
combination
with
α-PD-1,
anti-tumor
outcome
well
achieved
CT26
model.
Overall,
our
study
verifies
significance
precise
intracellular
delivery
introduces
promising
therapeutic
strategy
targeted
treatment
CRC.
Pharmacological Research,
Год журнала:
2022,
Номер
188, С. 106627 - 106627
Опубликована: Дек. 21, 2022
The
development
and
application
of
traditional
drugs
represented
by
small
molecule
chemical
biological
agents,
especially
inhibitors,
have
become
the
mainstream
drug
development.
In
recent
years,
targeted
protein
degradation
(TPD)
technology
has
one
most
promising
methods
to
remove
specific
disease-related
proteins
using
cell
self-destruction
mechanisms.
Many
different
TPD
strategies
are
emerging
based
on
ubiquitin-proteasome
system
(UPS)
autophagy-lysosomal
pathway
(ALP),
including
but
not
limited
proteolysis-targeting
chimeras
(PROTAC),
molecular
glues
(MG),
lysosome
targeting
(LYTAC),
chaperone-mediated
autophagy
(CMA)-targeting
chimeras,
autophagy-targeting
chimera
(AUTAC),
autophagosome-tethering
compound
(ATTEC),
(AUTOTAC).
advent
can
change
targets
in
human
cells
from
undruggable
druggable,
greatly
expanding
therapeutic
prospect
refractory
diseases
such
as
metabolic
syndrome.
Here,
we
summarize
latest
progress
major
technologies,
syndrome
look
forward
providing
new
insights
for
discovery.
