Chemical Society Reviews,
Год журнала:
2024,
Номер
53(19), С. 9582 - 9608
Опубликована: Янв. 1, 2024
Targeted
protein
degradation
(TPD)
has
emerged
as
a
revolutionary
paradigm
in
drug
discovery
and
development,
offering
promising
avenue
to
tackle
challenging
therapeutic
targets.
Unlike
traditional
approaches
that
focus
on
inhibiting
function,
TPD
aims
eliminate
proteins
of
interest
(POIs)
using
modular
chimeric
structures.
This
is
achieved
through
the
utilization
proteolysis-targeting
chimeras
(PROTACs),
which
redirect
POIs
E3
ubiquitin
ligases,
rendering
them
for
by
cellular
ubiquitin-proteasome
system
(UPS).
Additionally,
other
technologies
such
lysosome-targeting
(LYTACs)
autophagy-based
degraders
facilitate
transportation
endo-lysosomal
or
autophagy-lysosomal
pathways
degradation,
respectively.
Despite
significant
growth
preclinical
research,
many
fail
progress
beyond
this
stage
development.
Various
factors
contribute
limited
success
agents,
including
hurdle
inadequate
delivery
target
site.
Integrating
into
platforms
could
surmount
challenges
Journal of Medicinal Chemistry,
Год журнала:
2024,
Номер
67(9), С. 6906 - 6921
Опубликована: Апрель 25, 2024
DNA
damage
response
(DDR)
defects
in
cells
play
a
crucial
role
tumor
development
by
promoting
mutations.
These
mutations
create
vulnerabilities
specific
to
cancer
cells,
which
can
be
effectively
targeted
through
synthetic
lethality-based
therapies.
To
date,
numerous
small
molecule
DDR
inhibitors
have
been
identified,
and
some
of
them
already
approved
for
clinical
use.
However,
due
the
complexity
microenvironment,
may
occur
amino
acid
residues
targets.
affect
efficacy
targeting
pathways.
Therefore,
researchers
turned
their
attention
next-generation
repair
modulators,
particularly
those
based
on
PROTAC
technology.
From
this
perspective,
we
overviewed
recent
progress
DDR-targeting
degraders
therapy.
In
addition,
also
summarized
biological
functions
different
Finally,
challenges
future
directions
DDR-target
are
discussed
detail.
Asian Journal of Pharmaceutical Sciences,
Год журнала:
2024,
Номер
19(4), С. 100941 - 100941
Опубликована: Июль 10, 2024
Leucine-rich
α-2
glycoprotein
1
(LRG1),
a
secreted
glycoprotein,
has
been
identified
as
significantly
upregulated
in
renal
fibrosis,
potentially
exacerbating
the
condition
by
enhancing
TGF-β-Smad3-dependent
signaling
pathways.
Herein,
utilizing
our
developed
LRG1-targeting
peptide
for
LRG1
recruitment
and
lenalidomide
E3
ubiquitin
ligase
engagement,
we
an
advanced
proteolysis
targeting
chimera,
Chemical Society Reviews,
Год журнала:
2024,
Номер
53(19), С. 9582 - 9608
Опубликована: Янв. 1, 2024
Targeted
protein
degradation
(TPD)
has
emerged
as
a
revolutionary
paradigm
in
drug
discovery
and
development,
offering
promising
avenue
to
tackle
challenging
therapeutic
targets.
Unlike
traditional
approaches
that
focus
on
inhibiting
function,
TPD
aims
eliminate
proteins
of
interest
(POIs)
using
modular
chimeric
structures.
This
is
achieved
through
the
utilization
proteolysis-targeting
chimeras
(PROTACs),
which
redirect
POIs
E3
ubiquitin
ligases,
rendering
them
for
by
cellular
ubiquitin-proteasome
system
(UPS).
Additionally,
other
technologies
such
lysosome-targeting
(LYTACs)
autophagy-based
degraders
facilitate
transportation
endo-lysosomal
or
autophagy-lysosomal
pathways
degradation,
respectively.
Despite
significant
growth
preclinical
research,
many
fail
progress
beyond
this
stage
development.
Various
factors
contribute
limited
success
agents,
including
hurdle
inadequate
delivery
target
site.
Integrating
into
platforms
could
surmount
challenges
