Pharmaceutics,
Год журнала:
2023,
Номер
16(1), С. 4 - 4
Опубликована: Дек. 19, 2023
The
proper
viral
assembly
relies
on
both
nucleic
acids
and
structural
proteins.
Thus
a
biologically
active
agent
that
provides
the
degradation
of
one
these
key
proteins
and/or
destroys
factory
could
suppress
replication
efficiently.
nucleocapsid
protein
(N-protein)
is
for
SARS-CoV-2
virus.
As
bioactive
agent,
we
offer
modular
nanotransporter
(MNT)
developed
by
us,
which,
in
addition
to
an
antibody
mimetic
N-protein,
contains
amino
acid
sequence
attraction
Keap1
E3
ubiquitin
ligase.
This
should
lead
subsequent
N-protein.
We
have
shown
functional
properties
modules
within
MNT
permit
its
internalization
into
target
cells,
endosome
escape
cytosol,
binding
Using
flow
cytometry
western
blotting,
demonstrated
significant
N-protein
when
A549
A431
cells
transfected
with
plasmid
coding
were
incubated
MNTs.
proposed
MNTs
open
up
new
approach
treatment
diseases.
Signal Transduction and Targeted Therapy,
Год журнала:
2024,
Номер
9(1)
Опубликована: Ноя. 6, 2024
Abstract
Targeted
protein
degradation
(TPD)
represents
a
revolutionary
therapeutic
strategy
in
disease
management,
providing
stark
contrast
to
traditional
approaches
like
small
molecule
inhibitors
that
primarily
focus
on
inhibiting
function.
This
advanced
technology
capitalizes
the
cell’s
intrinsic
proteolytic
systems,
including
proteasome
and
lysosomal
pathways,
selectively
eliminate
disease-causing
proteins.
TPD
not
only
enhances
efficacy
of
treatments
but
also
expands
scope
applications.
Despite
its
considerable
potential,
faces
challenges
related
properties
drugs
their
rational
design.
review
thoroughly
explores
mechanisms
clinical
advancements
TPD,
from
initial
conceptualization
practical
implementation,
with
particular
proteolysis-targeting
chimeras
molecular
glues.
In
addition,
delves
into
emerging
technologies
methodologies
aimed
at
addressing
these
enhancing
efficacy.
We
discuss
significant
trials
highlight
promising
outcomes
associated
drugs,
illustrating
potential
transform
treatment
landscape.
Furthermore,
considers
benefits
combining
other
therapies
enhance
overall
effectiveness
overcome
drug
resistance.
The
future
directions
applications
are
explored,
presenting
an
optimistic
perspective
further
innovations.
By
offering
comprehensive
overview
current
innovations
faced,
this
assesses
transformative
revolutionizing
development
setting
stage
for
new
era
medical
therapy.
Viruses,
Год журнала:
2024,
Номер
16(3), С. 366 - 366
Опубликована: Фев. 27, 2024
Viral
proteases
are
an
important
target
for
drug
development,
since
they
can
modulate
vital
pathways
in
viral
replication,
maturation,
assembly
and
cell
entry.
With
the
(re)appearance
of
several
new
viruses
responsible
causing
diseases
humans,
like
West
Nile
virus
(WNV)
recent
severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2),
understanding
mechanisms
behind
blocking
protease’s
function
is
pivotal
development
antiviral
drugs
therapeutical
strategies.
Apart
from
directly
inhibiting
protease,
usually
by
targeting
its
active
site,
have
been
explored
to
impair
activity,
such
as
inducing
protein
aggregation,
allosteric
sites
or
degradation
cellular
proteasomes,
which
be
extremely
valuable
when
considering
emerging
drug-resistant
strains.
In
this
review,
we
aim
discuss
advances
on
a
broad
range
inhibitors,
therapies
molecular
approaches
inactivation
degradation,
giving
insight
different
possible
strategies
against
class
target.
Journal of Medicinal Chemistry,
Год журнала:
2024,
Номер
67(11), С. 8791 - 8816
Опубликована: Май 22, 2024
The
spread
of
the
influenza
virus
has
caused
devastating
pandemics
and
huge
economic
losses
worldwide.
Antiviral
drugs
with
diverse
action
modes
are
urgently
required
to
overcome
challenges
viral
mutation
drug
resistance,
targeted
protein
degradation
strategies
constitute
excellent
candidates
for
this
purpose.
Herein,
first
polymerase
acidic
(PA)
using
small-molecule
degraders
developed
by
hydrophobic
tagging
(HyT)
technology
effectively
combat
was
reported.
SAR
results
revealed
that
compound
Bulletin of the Korean Chemical Society,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 6, 2025
Abstract
Targeted
protein
degradation
(TPD)
is
a
relatively
novel
drug
discovery
strategy
that
could
help
break
through
the
limitations
of
traditional
small
molecule
inhibitors.
While
TPD
mostly
utilizes
diverse
E3
ligases
to
incorporate
ubiquitin‐proteasome
system
(UPS),
cereblon
(CRBN)
be
considered
one
most
successfully
adopted
ligases.
Thus,
expanding
scope
CRBN
ligands
has
received
tremendous
attention
overcome
related
issues,
such
as
selectivity
and
druggability.
In
this
study,
design
synthesis
benzosultam‐based
have
been
explored
by
replacement
lactam
in
lenalidomide
with
sultam.
The
sultam‐based
showed
binding
affinities
2‐20
times
stronger
than
lenalidomide,
presumably
from
additional
hydrogen
bonds
generated
extra
oxygen
atom
sultam
group,
supported
docking
studies.
This
research
highlights
potential
benzosultam
new
tool
for
CRBN‐mediated
strategies.
Expert Opinion on Drug Discovery,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 5, 2025
Targeted
protein
degradation
(TPD)
is
a
cutting-edge
technology
that
provides
new
avenues
for
drug
discovery
and
development.
PROteolysis
TArgeting
Chimeras
(PROTACs)
are
the
most
established
advanced
TPD
strategy,
enabling
selective
of
disease-associated
'undruggable'
proteins
interest
(POIs)
by
leveraging
cell's
natural
machinery.
To
confirm
PROTAC-induced
proximity
drives
degradation,
target
validation
ternary
complex
formation
must
be
thoroughly
assessed.
In
this
perspective,
authors
detail
some
widely
used
in
silico,
structural,
vitro,
cellulo
methods
to
validate
PROTAC
engagement
formation.
Additionally,
they
discuss
growing
use
PROTACs
as
chemical
probes
novel
identification
validation.
Target
essential
approach,
ongoing
studies
should
prioritize
confirming
using
assays
conducted
under
physiologically
relevant
cellular
conditions.
The
believe
proteomics
analyses
among
valuable
tools
elucidating
mechanism,
selectivity,
outcomes
PROTACs.
They
also
remain
optimistic
about
future
development
their
engagement.
While
rapidly
advancing,
it
still
holds
vast
opportunities
exploration,
offering
significant
potential
further
both
biological
research
drive
drugs.
