MedComm,
Journal Year:
2022,
Volume and Issue:
3(4)
Published: Oct. 13, 2022
Compared
with
traditional
therapies,
targeted
therapy
has
merits
in
selectivity,
efficacy,
and
tolerability.
Small
molecule
inhibitors
are
one
of
the
primary
therapies
for
cancer.
Due
to
their
advantages
a
wide
range
targets,
convenient
medication,
ability
penetrate
into
central
nervous
system,
many
efforts
have
been
devoted
developing
more
small
inhibitors.
To
date,
88
approved
by
United
States
Food
Drug
Administration
treat
cancers.
Despite
remarkable
progress,
cancer
treatment
still
face
obstacles,
such
as
low
response
rate,
short
duration
response,
toxicity,
biomarkers,
resistance.
better
promote
development
targeting
cancers,
we
comprehensively
reviewed
involved
all
agents
pivotal
drug
candidates
clinical
trials
arranged
signaling
pathways
classification
We
discussed
lessons
learned
from
these
agents,
proper
strategies
overcome
resistance
arising
different
mechanisms,
combination
concerned
Through
our
review,
hoped
provide
insights
perspectives
research
treatment.
Signal Transduction and Targeted Therapy,
Journal Year:
2022,
Volume and Issue:
7(1)
Published: April 4, 2022
Abstract
Traditional
drug
discovery
mainly
focuses
on
direct
regulation
of
protein
activity.
The
development
and
application
activity
modulators,
particularly
inhibitors,
has
been
the
mainstream
in
development.
In
recent
years,
PROteolysis
TArgeting
Chimeras
(PROTAC)
technology
emerged
as
one
most
promising
approaches
to
remove
specific
disease-associated
proteins
by
exploiting
cells’
own
destruction
machinery.
addition
PROTAC,
many
different
targeted
degradation
(TPD)
strategies
including,
but
not
limited
to,
molecular
glue,
Lysosome-Targeting
Chimaera
(LYTAC),
Antibody-based
PROTAC
(AbTAC),
are
emerging.
These
technologies
have
only
greatly
expanded
scope
TPD,
also
provided
fresh
insights
into
discovery.
Here,
we
summarize
advances
major
TPD
technologies,
discuss
their
potential
applications,
hope
provide
a
prime
for
both
biologists
chemists
who
interested
this
vibrant
field.
Chemical Society Reviews,
Journal Year:
2022,
Volume and Issue:
51(12), P. 5214 - 5236
Published: Jan. 1, 2022
Proteolysis-targeting
chimeras
(PROTACs)
are
heterobifunctional
molecules
consisting
of
one
ligand
that
binds
to
a
protein
interest
(POI)
and
another
can
recruit
an
E3
ubiquitin
ligase.
The
chemically-induced
proximity
between
the
POI
ligase
results
in
ubiquitination
subsequent
degradation
by
ubiquitin-proteasome
system
(UPS).
event-driven
mechanism
action
(MOA)
PROTACs
offers
several
advantages
compared
traditional
occupancy-driven
small
molecule
inhibitors,
such
as
catalytic
nature,
reduced
dosing
frequency,
more
potent
longer-lasting
effect,
added
layer
selectivity
reduce
potential
toxicity,
efficacy
face
drug-resistance
mechanisms,
targeting
nonenzymatic
functions,
expanded
target
space.
Here,
we
highlight
important
milestones
briefly
discuss
lessons
learned
about
targeted
(TPD)
recent
years
conjecture
on
efforts
still
needed
expand
toolbox
for
PROTAC
discovery
ultimately
provide
promising
therapeutics.
Experimental & Molecular Medicine,
Journal Year:
2022,
Volume and Issue:
54(10), P. 1670 - 1694
Published: Oct. 12, 2022
Abstract
Since
the
initial
clinical
approval
in
late
1990s
and
remarkable
anticancer
effects
for
certain
types
of
cancer,
molecular
targeted
therapy
utilizing
small
molecule
agents
or
therapeutic
monoclonal
antibodies
acting
as
signal
transduction
inhibitors
has
served
a
fundamental
backbone
precision
medicine
cancer
treatment.
These
approaches
are
now
used
clinically
first-line
various
human
cancers.
Compared
to
conventional
chemotherapy,
have
efficient
with
fewer
side
effects.
However,
emergence
drug
resistance
is
major
drawback
therapy,
several
strategies
been
attempted
improve
efficacy
by
overcoming
such
resistance.
Herein,
we
summarize
current
knowledge
regarding
agents,
including
classification,
brief
biology
target
kinases,
mechanisms
action,
examples
perspectives
future
development.
Chemical Society Reviews,
Journal Year:
2022,
Volume and Issue:
51(16), P. 7066 - 7114
Published: Jan. 1, 2022
Proteolysis
targeting
chimeras
(PROTACs)
technology
is
a
novel
and
promising
therapeutic
strategy
using
small
molecules
to
induce
ubiquitin-dependent
degradation
of
proteins.
Signal Transduction and Targeted Therapy,
Journal Year:
2022,
Volume and Issue:
7(1)
Published: June 9, 2022
Abstract
PROteolysis
TArgeting
Chimeras
(PROTACs)
technology
is
a
new
protein-degradation
strategy
that
has
emerged
in
recent
years.
It
uses
bifunctional
small
molecules
to
induce
the
ubiquitination
and
degradation
of
target
proteins
through
ubiquitin–proteasome
system.
PROTACs
can
not
only
be
used
as
potential
clinical
treatments
for
diseases
such
cancer,
immune
disorders,
viral
infections,
neurodegenerative
diseases,
but
also
provide
unique
chemical
knockdown
tools
biological
research
catalytic,
reversible,
rapid
manner.
In
2019,
our
group
published
review
article
“PROTACs:
great
opportunities
academia
industry”
journal,
summarizing
representative
compounds
reported
before
end
2019.
past
2
years,
entire
field
protein
experienced
development,
including
large
increase
number
papers
on
small-molecule
degraders
have
entered
will
enter
stage.
addition
PROTAC
molecular
glue
technology,
other
technologies
are
developing
rapidly.
this
article,
we
mainly
summarize
related
targets
2020–2021
present
researchers
exciting
developments
degradation.
The
problems
need
solved
briefly
introduced.
Journal of Medicinal Chemistry,
Journal Year:
2024,
Volume and Issue:
67(14), P. 11622 - 11655
Published: July 12, 2024
This
Perspective
is
a
continuation
of
our
analysis
U.S.
FDA-approved
small-molecule
drugs
(1938-2012)
containing
nitrogen
heterocycles.
In
this
study
we
report
drug
structure
and
property
analyses
321
unique
new
approved
from
January
2013
to
December
2023
as
well
information
about
frequency
important
heteroatoms
such
sulfur
fluorine
key
small
substituents
(CN
NO
Chemical Society Reviews,
Journal Year:
2022,
Volume and Issue:
51(13), P. 5330 - 5350
Published: Jan. 1, 2022
This
tutorial
review
discusses
the
convergence
of
drug
delivery
systems
and
PROTACs,
surveys
burgeoning
PROTAC
strategies,
summarizes
their
design
principles,
clarifies
challenges,
outlooks
future
translational
opportunities.
