Journal of Medicinal Chemistry,
Journal Year:
2019,
Volume and Issue:
63(1), P. 23 - 39
Published: Aug. 15, 2019
Epigenetic
regulation
orchestrates
many
cellular
processes
and
greatly
influences
key
disease
mechanisms.
Histone
deacetylase
(HDAC)
enzymes
play
a
crucial
role
either
as
biomarkers
or
therapeutic
targets
owing
to
their
involvement
in
specific
pathophysiological
pathways.
Beyond
well-characterized
histone
modifiers,
HDACs
also
interact
with
several
nonhistone
substrates
increased
expression
has
been
highlighted
diseases.
The
HDAC6
isoform,
due
its
unique
cytoplasmic
localization,
modulates
the
acetylation
status
of
tubulin,
HSP90,
TGF-β,
peroxiredoxins.
exerts
noncatalytic
activities
through
interaction
ubiquitin.
Both
catalytic
functions
are
being
actively
studied
field
rare
disorders
beyond
well-established
carcinogenesis.
This
Perspective
outlines
application
HDAC(6)
inhibitors
diseases,
such
Rett
syndrome,
inherited
retinal
disorders,
idiopathic
pulmonary
fibrosis,
Charcot–Marie–Tooth
disease,
highlighting
potential
innovative
targeted
disease-modifying
agents.
Chemical Reviews,
Journal Year:
2018,
Volume and Issue:
118(3), P. 1216 - 1252
Published: Feb. 6, 2018
Post-translational
acetylation
of
lysine
residues
has
emerged
as
a
key
regulatory
mechanism
in
all
eukaryotic
organisms.
Originally
discovered
1963
unique
modification
histones,
marks
are
now
found
on
thousands
nonhistone
proteins
located
virtually
every
cellular
compartment.
Here
we
summarize
findings
the
field
protein
over
past
20
years
with
focus
recent
discoveries
nuclear,
cytoplasmic,
and
mitochondrial
compartments.
Collectively,
these
have
elevated
major
post-translational
modification,
underscoring
its
physiological
relevance
gene
regulation,
cell
signaling,
metabolism,
disease.
Genes,
Journal Year:
2020,
Volume and Issue:
11(5), P. 556 - 556
Published: May 15, 2020
Histone
deacetylases
(HDACs)
are
evolutionary
conserved
enzymes
which
operate
by
removing
acetyl
groups
from
histones
and
other
protein
regulatory
factors,
with
functional
consequences
on
chromatin
remodeling
gene
expression
profiles.
We
provide
here
a
review
the
recent
knowledge
accrued
zinc-dependent
HDAC
family
across
different
species,
tissues,
human
pathologies,
specifically
focusing
role
of
inhibitors
as
anti-cancer
agents.
will
investigate
chemical
specificity
HDACs
discuss
their
in
interactome
members
chromatin-binding
complexes.
Frontiers in Cell and Developmental Biology,
Journal Year:
2020,
Volume and Issue:
8
Published: Sept. 29, 2020
Genetic
mutations
and
abnormal
gene
regulation
are
key
mechanisms
underlying
tumorigenesis.
Nucleosomes,
which
consist
of
DNA
wrapped
around
histone
cores,
represent
the
basic
units
chromatin.
The
fifth
amino
group
(Nε)
lysine
residues
is
a
common
site
for
post-translational
modifications
(PTMs),
these,
acetylation
second
most
common.
Histone
modulated
by
acetyltransferases
(HATs)
deacetylases
(HDACs),
involved
in
expression.
Over
past
two
decades,
numerous
studies
characterizing
HDACs
HDAC
inhibitors
(HDACi)
have
provided
novel
exciting
insights
concerning
their
biological
potential
anti-cancer
treatments.
In
this
review,
we
detail
diverse
structures
functions,
including
transcriptional
regulation,
metabolism,
angiogenesis,
damage
response,
cell
cycle,
apoptosis,
protein
degradation,
immunity
other
several
physiological
processes.
We
also
highlight
avenues
to
use
HDACi
as
novel,
precision
cancer
Chemical Reviews,
Journal Year:
2018,
Volume and Issue:
119(2), P. 1323 - 1455
Published: Sept. 7, 2018
Metalloenzymes
are
central
to
a
wide
range
of
essential
biological
activities,
including
nucleic
acid
modification,
protein
degradation,
and
many
others.
The
role
metalloenzymes
in
these
processes
also
makes
them
for
the
progression
diseases
and,
as
such,
attractive
targets
therapeutic
intervention.
Increasing
awareness
play
disease
their
importance
class
has
amplified
interest
development
new
strategies
develop
inhibitors
ultimately
useful
drugs.
In
this
Review,
we
provide
broad
overview
several
drug
discovery
efforts
focused
on
attempt
map
out
current
landscape
high-value
metalloenzyme
targets.
Nature Communications,
Journal Year:
2017,
Volume and Issue:
8(1)
Published: May 18, 2017
Abstract
Cationic
polyamines
such
as
spermidine
and
spermine
are
critical
in
all
forms
of
life,
they
regulate
the
function
biological
macromolecules.
Intracellular
polyamine
metabolism
is
regulated
by
reversible
acetylation
dysregulated
associated
with
neoplastic
diseases
colon
cancer,
prostate
cancer
neuroblastoma.
Here
we
report
that
histone
deacetylase
10
(HDAC10)
a
robust
deacetylase,
using
recombinant
enzymes
from
Homo
sapiens
(human)
Danio
rerio
(zebrafish).
The
2.85
Å-resolution
crystal
structure
zebrafish
HDAC10
complexed
transition-state
analogue
inhibitor
reveals
glutamate
gatekeeper
sterically
constricted
active
site
confer
specificity
for
N
8
-acetylspermidine
hydrolysis
disfavour
acetyllysine
hydrolysis.
Both
known
to
promote
cellular
survival
through
autophagy.
Accordingly,
this
work
sets
foundation
studying
chemical
biology
autophagy
structure-based
design
inhibitors
may
also
serve
new
leads
chemotherapy.
Cancers,
Journal Year:
2021,
Volume and Issue:
13(4), P. 634 - 634
Published: Feb. 5, 2021
The
increasing
knowledge
of
molecular
drivers
tumorigenesis
has
fueled
targeted
cancer
therapies
based
on
specific
inhibitors.
Beyond
“classic”
oncogene
inhibitors,
epigenetic
therapy
is
an
emerging
field.
Epigenetic
alterations
can
occur
at
any
time
during
progression,
altering
the
structure
chromatin,
accessibility
for
transcription
factors
and
thus
genes.
They
rely
post-translational
histone
modifications,
particularly
acetylation
lysine
residues,
are
determined
by
inverse
action
acetyltransferases
(HATs)
deacetylases
(HDACs).
Importantly,
HDACs
often
aberrantly
overexpressed,
predominantly
leading
to
transcriptional
repression
tumor
suppressor
Thus,
deacetylase
inhibitors
(HDACis)
powerful
drugs,
with
some
already
approved
certain
hematological
cancers.
Albeit
HDACis
show
activity
in
solid
tumors
as
well,
further
refinement
development
novel
drugs
needed.
This
review
describes
capability
influence
various
pathways
and,
this
knowledge,
gives
a
comprehensive
overview
preclinical
clinical
studies
tumors.
A
particular
focus
placed
strategies
achieving
higher
efficacy
combination
therapies,
including
phosphoinositide
3-kinase
(PI3K)-EGFR
hormone-
or
immunotherapy.
also
includes
new
bifunctional
well
approaches
HDAC
degradation
via
PROteolysis-TArgeting
Chimeras
(PROTACs).