Medicine Plus,
Journal Year:
2024,
Volume and Issue:
1(1), P. 100004 - 100004
Published: Jan. 12, 2024
Degrader
technologies
provide
unprecedented
strategies
to
tackle
diseases
caused
by
pathogenic
proteins
that
are
difficult
target
the
traditional
inhibitor
approach.
One
pioneering
technology,
proteolysis-targeting
chimera
(PROTAC),
has
revolutionized
small-molecule
drug
discovery.
Meanwhile,
PROTACs
hijack
ubiquitination-proteasome
pathway,
which
is
incapable
of
degrading
certain
categories
targets.
To
address
this
limitation,
scientists
introduced
autophagy-tethering
compounds
(ATTECs),
capitalizing
on
autophagosome
protein
LC3
selectively
break
down
both
and
organelles.
This
review
explores
multiple
dimensions
ATTECs,
focusing
their
mechanisms
action
potential
applications
in
Chemical Society Reviews,
Journal Year:
2023,
Volume and Issue:
52(11), P. 3663 - 3740
Published: Jan. 1, 2023
Carbohydrates
are
essential
mediators
of
many
processes
in
health
and
disease.
The
development
glycomimetics
as
inhibitors
modulators
their
lectin
receptors
has
been
a
success
story
with
numerous
molecules
reaching
clinical
stages.
Signal Transduction and Targeted Therapy,
Journal Year:
2024,
Volume and Issue:
9(1)
Published: Nov. 26, 2024
Epigenetics
governs
a
chromatin
state
regulatory
system
through
five
key
mechanisms:
DNA
modification,
histone
RNA
remodeling,
and
non-coding
regulation.
These
mechanisms
their
associated
enzymes
convey
genetic
information
independently
of
base
sequences,
playing
essential
roles
in
organismal
development
homeostasis.
Conversely,
disruptions
epigenetic
landscapes
critically
influence
the
pathogenesis
various
human
diseases.
This
understanding
has
laid
robust
theoretical
groundwork
for
developing
drugs
that
target
epigenetics-modifying
pathological
conditions.
Over
past
two
decades,
growing
array
small
molecule
targeting
such
as
methyltransferase,
deacetylase,
isocitrate
dehydrogenase,
enhancer
zeste
homolog
2,
have
been
thoroughly
investigated
implemented
therapeutic
options,
particularly
oncology.
Additionally,
numerous
epigenetics-targeted
are
undergoing
clinical
trials,
offering
promising
prospects
benefits.
review
delineates
epigenetics
physiological
contexts
underscores
pioneering
studies
on
discovery
implementation
drugs.
include
inhibitors,
agonists,
degraders,
multitarget
agents,
aiming
to
identify
practical
challenges
avenues
future
research.
Ultimately,
this
aims
deepen
epigenetics-oriented
strategies
further
application
settings.
Biochemistry,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 10, 2025
Proteolysis-targeting
chimeras
(PROTACs)
represent
a
transformative
advancement
in
drug
discovery,
offering
method
to
degrade
specific
intracellular
proteins.
Unlike
traditional
inhibitors,
PROTACs
are
bifunctional
molecules
that
target
proteins
for
elimination,
enabling
the
potential
treatment
of
previously
"undruggable"
This
concept,
pioneered
by
Crews
and
his
team,
introduced
use
small
link
protein
an
E3
ubiquitin
ligase,
inducing
ubiquitination
subsequent
degradation
protein.
By
promoting
rather
than
merely
inhibiting
function,
present
novel
therapeutic
strategy
with
enhanced
specificity
effectiveness,
especially
areas
such
as
cancer
neurodegenerative
diseases.
Since
their
initial
field
PROTAC
research
has
rapidly
expanded
numerous
now
designed
wide
range
disease-relevant
The
substantial
research,
investment,
collaboration
across
academia
pharmaceutical
industry
reflect
growing
interest
PROTACs.
Review
discusses
journey
from
discovery
clinical
trials,
highlighting
advancements
challenges.
Additionally,
recent
developments
fluorescent
photogenic
PROTACs,
used
real-time
tracking
degradation,
presented,
showcasing
evolving
targeted
therapy.
Journal of Controlled Release,
Journal Year:
2025,
Volume and Issue:
380, P. 524 - 538
Published: Feb. 12, 2025
Receptor-mediated
endocytosis
plays
a
crucial
role
in
the
success
of
numerous
therapies
and
remains
central
to
advancing
drug
development.
This
process
begins
with
ligand
binding
specific
receptors,
triggering
internalization
intracellular
trafficking
receptor-ligand
complexes.
These
complexes
are
subsequently
directed
into
distinct
routes,
either
toward
lysosomal
degradation
or
recycling
cell
surface,
implications
for
therapeutic
outcomes.
review
examines
interactions
as
key
modulators
endocytosis,
emphasizing
their
shaping
design
efficacy.
Advances
selecting
pairs
engineering
ligands
optimized
properties
have
enabled
precise
control
over
internalization,
endosomal
sorting,
trafficking,
providing
tailored
solutions
diverse
applications.
Leveraging
these
insights,
strategies
such
RNA-based
therapies,
antibody-drug
conjugates
(ADCs),
targeted
protein
(TPD)
platforms
been
refined
selectively
avoid
promote
degradation,
thereby
enhancing
By
bridging
fundamental
mechanisms
receptor-mediated
innovative
approaches,
this
offers
framework
precision
medicine.
The Innovation,
Journal Year:
2023,
Volume and Issue:
4(3), P. 100413 - 100413
Published: March 15, 2023
Targeted
protein
degradation
(TPD)
is
emerging
as
a
strategy
to
overcome
the
limitations
of
traditional
small-molecule
inhibitors.
Proteolysis-targeting
chimera
(PROTAC)
technology
can
be
used
target
proteins
by
hijacking
ubiquitin-proteasome
system.
Conceptually,
PROTAC
aims
"undruggable"
majority
in
human
proteome.
Through
constant
exploration
and
optimization
PROTACs
exploitation
other
TPD
strategies
over
two
decades,
has
expanded
from
theoretical
studies
clinical
strategies,
with
practical
applications
oncological,
immunological,
diseases.
In
this
review,
we
introduce
mechanisms,
features,
molecular
targets
orthodox
summarize
drugs
under
study
cancer
therapeutics
trials.
We
also
discuss
derivatives
such
lysosome-targeting
chimeras,
autophagy-targeting
glue
strategies.
Collectively,
summarized
herein
support
full
potential
biomedical
industry.
Advanced Science,
Journal Year:
2023,
Volume and Issue:
10(19)
Published: April 21, 2023
Abstract
Preventing
islet
β
‐cells
death
is
crucial
for
treating
type
2
diabetes
mellitus
(T2DM).
Currently,
clinical
drugs
are
being
developed
to
improve
the
quality
of
T2DM
care
and
self‐care,
but
focused
on
reducing
islets
‐cell
lacking.
Given
that
in
dominated
ultimately
by
excessive
reactive
oxygen
species
(ROS),
eliminating
ROS
a
highly
promising
therapeutic
strategy.
Nevertheless,
no
antioxidants
have
been
approved
therapy
because
most
them
cannot
meet
long‐term
stable
elimination
without
eliciting
toxic
side‐effects.
Here,
it
proposed
restore
endogenous
antioxidant
capacity
efficiently
prevent
using
selenium
nanodots
(SENDs),
prodrug
enzyme
glutathione
peroxidase
1
(GPX1).
SENDs
not
only
scavenge
effectively,
also
“send”
precisely
with
response
greatly
enhance
increasing
GPX1
expression.
Therefore,
rescue
restoring
mitophagy
alleviating
endoplasmic
reticulum
stress
(ERS),
demonstrate
much
stronger
efficacy
than
first‐line
drug
metformin
treatment.
Overall,
this
strategy
highlights
great
application
prospects
SENDs,
offering
paradigm
an
MedComm,
Journal Year:
2023,
Volume and Issue:
4(3)
Published: May 29, 2023
Proteolysis
targeting
chimera
(PROTAC)
technology
has
become
a
powerful
strategy
in
drug
discovery,
especially
for
undruggable
targets/proteins.
A
typical
PROTAC
degrader
consists
of
three
components:
small
molecule
that
binds
to
target
protein,
an
E3
ligase
ligand
(consisting
and
its
recruiter),
chemical
linker
hooks
first
two
components
together.
In
the
past
20
years,
we
have
witnessed
advancement
multiple
degraders
into
clinical
trials
anticancer
therapies.
However,
one
major
challenges
is
only
very
limited
number
recruiters
are
currently
available
as
targeted
protein
degradation
(TPD),
although
human
genome
encodes
more
than
600
ligases.
Thus,
there
urgent
need
identify
additional
effective
TPD
applications.
this
review,
summarized
existing
RING-type
ubiquitin
their
act
ligands
application
discovery.
We
believe
review
could
serve
reference
future
development
efficient
cancer
discovery
development.
Journal of Medicinal Chemistry,
Journal Year:
2023,
Volume and Issue:
66(3), P. 1700 - 1711
Published: Jan. 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.
