Medicinal Research Reviews,
Journal Year:
2022,
Volume and Issue:
42(3), P. 1280 - 1342
Published: Jan. 10, 2022
Abstract
Proteolysis
targeting
chimaeras
(PROTACs)
is
a
cutting
edge
and
rapidly
growing
technique
for
new
drug
discovery
development.
Currently,
the
largest
challenge
in
molecular
design
development
of
PROTACs
efficient
identification
potent
drug‐like
degraders.
This
review
aims
to
comprehensively
summarize
analyse
state‐of‐the‐art
methods
strategies
PROTACs.
We
provide
detailed
illustration
general
principles
tactics
designing
PROTACs,
highlight
representative
case
studies,
discuss
advantages
limitations
these
strategies.
Particularly,
structure‐based
rational
PROTAC
emerging
types
(e.g.,
homo‐PROTACs,
multitargeting
photo‐control
PROTAC‐based
conjugates)
will
be
focused
on.
Journal of Medicinal Chemistry,
Journal Year:
2021,
Volume and Issue:
64(5), P. 2419 - 2435
Published: Feb. 22, 2021
Bromodomain
and
extraterminal
(BET)
proteins
bind
acetylated
lysine
residues
in
histones
nonhistone
via
tandem
bromodomains
regulate
chromatin
dynamics,
cellular
processes,
disease
procession.
Thus
targeting
BET
is
a
promising
strategy
for
treating
various
diseases,
especially
malignant
tumors
chronic
inflammation.
Many
pan-BET
small-molecule
inhibitors
have
been
described,
some
of
them
are
clinical
evaluation.
Nevertheless,
the
limited
efficacy
current
also
evident
has
inspired
development
new
technologies
to
improve
their
outcomes
minimize
unwanted
side
effects.
In
this
Review,
we
summarize
latest
protein
characteristics
biological
functions
BRD4
as
an
example
proteins,
analyze
status
preclinical
resistance
mechanisms,
discuss
recent
advances
BRD4-selective
inhibitors,
dual-target
proteolysis
chimera
degraders,
protein–protein
interaction
inhibitors.
Signal Transduction and Targeted Therapy,
Journal Year:
2022,
Volume and Issue:
7(1)
Published: Dec. 29, 2022
Metabolic
reprogramming
is
involved
in
the
pathogenesis
of
not
only
cancers
but
also
neurodegenerative
diseases,
cardiovascular
and
infectious
diseases.
With
progress
metabonomics
proteomics,
metabolites
have
been
found
to
affect
protein
acylations
through
providing
acyl
groups
or
changing
activities
acyltransferases
deacylases.
Reciprocally,
acylation
key
cellular
processes
relevant
physiology
such
as
stability,
subcellular
localization,
enzyme
activity,
transcriptional
protein-protein
interactions
protein-DNA
interactions.
Herein,
we
summarize
functional
diversity
mechanisms
eight
kinds
nonhistone
physiological
progression
several
We
highlight
recent
development
inhibitors
for
acyltransferase,
deacylase,
reader
proteins
their
potential
applications
drug
discovery.
Chemical Society Reviews,
Journal Year:
2022,
Volume and Issue:
51(10), P. 3886 - 3897
Published: Jan. 1, 2022
This
review
illustrates
the
design
of
antibody
conjugates
which
employ
chimeric
protein
degraders
(
i.e.
,
PROTACs)
as
payloads
and
summarizes
examples
such
entities
that
are
currently
known
in
scientific
patent
literature.
Medicinal Research Reviews,
Journal Year:
2022,
Volume and Issue:
42(3), P. 1280 - 1342
Published: Jan. 10, 2022
Abstract
Proteolysis
targeting
chimaeras
(PROTACs)
is
a
cutting
edge
and
rapidly
growing
technique
for
new
drug
discovery
development.
Currently,
the
largest
challenge
in
molecular
design
development
of
PROTACs
efficient
identification
potent
drug‐like
degraders.
This
review
aims
to
comprehensively
summarize
analyse
state‐of‐the‐art
methods
strategies
PROTACs.
We
provide
detailed
illustration
general
principles
tactics
designing
PROTACs,
highlight
representative
case
studies,
discuss
advantages
limitations
these
strategies.
Particularly,
structure‐based
rational
PROTAC
emerging
types
(e.g.,
homo‐PROTACs,
multitargeting
photo‐control
PROTAC‐based
conjugates)
will
be
focused
on.
