Journal of Medicinal Chemistry,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Dec. 20, 2024
Recent
studies
have
identified
selective
peroxisome
proliferator-activated
receptor
γ
(PPARγ)
modulators,
which
synergistically
engage
in
the
inhibition
mechanism
of
PPARγ-Ser273
phosphorylation,
as
a
promising
approach
for
developing
safer
and
more
effective
antidiabetic
drugs.
Herein,
we
present
design,
synthesis,
evaluation
new
class
organo-Se
compounds,
namely,
benzothiaselenazole-1-oxides
(BTSAs),
acting
potent,
reversible,
PPARγ
covalent
modulators.
Notably,
Journal of Cellular and Molecular Medicine,
Journal Year:
2025,
Volume and Issue:
29(4)
Published: Feb. 1, 2025
ABSTRACT
The
family
of
protein
arginine
methyltransferases
(PRMTs)
occupies
an
important
position
in
biology,
especially
during
the
initiation
and
development
cancer.
PRMT3
CARM1(also
known
as
PRMT4),
being
type
I
methyltransferases,
are
key
controlling
tumour
progression
by
catalysing
mono‐methylation
asymmetric
di‐methylation
both
histone
non‐histone
substrates.
This
paper
reviews
functions
potential
therapeutic
target
value
CARM1
a
variety
cancers.
Studies
have
identified
abnormal
expressions
several
malignancies,
closely
linked
to
cancer
progression,
advancement,
resistance
treatment.
Such
hepatocellular
carcinoma,
colorectal
cancer,
ovarian
endometrial
These
findings
offer
new
strategies
directions
for
treatment,
enhancing
effectiveness
conventional
treatment
methods.
Journal of Biological Chemistry,
Journal Year:
2025,
Volume and Issue:
unknown, P. 108271 - 108271
Published: Feb. 1, 2025
Hyperglycemia
is
a
hallmark
of
metabolic
disorders,
yet
the
precise
mechanisms
linking
epigenetic
regulation
to
glucose
metabolism
remain
underexplored.
Coactivator-associated
arginine
methyltransferase
1
(CARM1),
type
I
histone
methyltransferase,
promotes
transcriptional
activation
through
methylation
H3
at
residues
H3R17
and
H3R26.
Here,
we
identify
novel
mechanism
by
which
metformin,
widely
prescribed
antidiabetic
drug,
inhibits
CARM1
activity.
Using
biochemical
biophysical
assays,
show
that
metformin
binds
substrate-binding
site
CARM1,
reducing
levels
in
CARM1-overexpressing
hepatic
cells
liver
tissues
from
metformin-fed
mice.
This
modulation
suppresses
expression
gluconeogenic
enzymes
(G6Pase,
FBPase,
PCK1),
thereby
reversing
CARM1-induced
glycolytic
suppression
regulating
gluconeogenesis.
Importantly,
does
not
alter
protein
its
recruitment
gene
promoters
but
diminishes
H3R17me2a
marks
these
loci.
Our
findings
reveal
previously
unrecognized
action,
offering
new
therapeutic
insights
for
hyperglycemia
management.
Advanced Science,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 10, 2025
Abstract
In
mammals,
the
activation
of
thermogenic
adipocytes,
such
as
beige
and
brown
can
significantly
increase
overall
energy
expenditure,
offering
a
promising
strategy
to
combat
metabolic
diseases.
Despite
its
considerable
potential,
regulatory
mechanisms
governing
this
remain
largely
elusive.
This
study
bridges
gap
by
elucidating
that
tripartite
motif
56
(TRIM56),
an
E3
ubiquitin
ligase,
is
upregulated
in
response
cold
stimuli,
thereby
promoting
recruitment
adipocytes.
Notably,
overexpression
TRIM56
adipocytes
shown
help
mice
maintain
core
temperature
under
conditions,
well
confer
protection
against
diet‐induced
obesity.
Mechanistically,
facilitates
degradation
transducin‐like
enhancer
protein
3
(TLE3)
K48‐linked
ubiquitination,
which
subsequently
triggers
genes
subcutaneousl
white
adipose
tissue
improved
profiles.
These
findings
unveil
novel
function
for
adipocyte
browning,
suggesting
potential
therapeutic
target
treatment
disorders.
Scientific Reports,
Journal Year:
2024,
Volume and Issue:
14(1)
Published: March 20, 2024
Abstract
The
feed-forward
loop
between
the
transcription
factors
Ppar-gamma
and
C/ebp-alpha
is
critical
for
lineage
commitment
during
adipocytic
differentiation.
interacts
with
epigenetic
cofactors
to
activate
downstream
gene
expression
program.
Therefore,
knowledge
of
associated
Ppar-gamma,
central
understanding
adipocyte
differentiation
in
normal
disease.
We
found
that
Prmt6
present
on
promoter.
It
contributes
repression
expression,
part
through
its
ability
induce
H3R2me2a.
During
differentiation,
reduced
methyltransferase
leaves
promoters.
As
a
result,
upregulated
program
established.
Inhibition
by
small
molecule
enhances
adipogenesis,
opening
up
possibility
manipulation
Our
data
provide
detailed
information
molecular
mechanism
controlling
Ppar-gamma–C/ebp-alpha
loop.
Thus,
they
advance
our
adipogenesis
aberrant
adipogenesis.
Biomedicine & Pharmacotherapy,
Journal Year:
2024,
Volume and Issue:
178, P. 117281 - 117281
Published: Aug. 12, 2024
Extensive
research
has
shown
that
PR
domain
16
(PRDM16)
plays
a
critical
role
in
adipose
tissue
metabolism,
including
processes
such
as
browning
and
thermogenesis
of
adipocytes,
beigeing
adipogenic
differentiation
myoblasts.
These
functions
have
been
associated
with
diseases
obesity
diabetes.
Additionally,
PRDM16
correlated
various
other
conditions,
migraines,
heterochromatin
abnormalities,
metabolic
syndrome,
cardiomyopathy,
sarcopenia,
nonsyndromic
cleft
lip,
essential
hypertension,
among
others.
However,
there
is
currently
no
systematic
or
comprehensive
conclusion
regarding
the
mechanism
human
tumours,
haematologic
solid
tumours.
The
aim
this
review
to
provide
an
overview
progress
on
tumours
by
incorporating
recent
literature
findings.
Furthermore,
we
explore
prospects
precise
diagnosis
treatment
Protein and Peptide Letters,
Journal Year:
2023,
Volume and Issue:
31(1), P. 25 - 42
Published: Dec. 29, 2023
Protein
arginine
methylation
stands
as
a
prevalent
post-translational
modification
process,
exerting
vital
roles
in
cellular
signal
transduction,
gene
expression,
and
cell
cycle
regulation.
Amidst
the
protein
methyltransferase
(PRMT)
family,
PRMT2
less
explored
constituent.
Nonetheless,
its
regulatory
transcriptional
regulation,
post-transcriptional
modification,
activity
immunoregulation,
developmental
regulation
have
garnered
attention.
These
capabilities
enable
to
exert
pivotal
functions
certain
malignancies,
metabolic
disorders,
inflammatory
diseases,
atherosclerosis.
In
this
review,
we
highlight
structure
of
PRMT2,
emphasizing
association
with
diseases.
We
also
discuss
inhibitors
explore
potential
for
therapeutic
targeting.
Diabetes & Metabolism Journal,
Journal Year:
2024,
Volume and Issue:
48(4), P. 487 - 502
Published: July 24, 2024
Cardiovascular
diseases
(CVDs)
and
metabolic
disorders
stand
as
formidable
challenges
that
significantly
impact
the
clinical
outcomes
living
quality
for
afflicted
individuals.
An
intricate
comprehension
of
underlying
mechanisms
is
paramount
development
efficacious
therapeutic
strategies.
Protein
arginine
methyltransferases
(PRMTs),
a
class
enzymes
responsible
precise
regulation
protein
methylation,
have
ascended
to
pivotal
roles
emerged
crucial
regulators
within
intrinsic
pathophysiology
these
diseases.
Herein,
we
review
recent
advancements
in
research
elucidating
on
multifaceted
involvements
PRMTs
cardiovascular
system
diseases,
contributing
deepen
our
understanding
pathogenesis
progression
maladies.
In
addition,
this
provides
comprehensive
analysis
unveil
distinctive
across
diverse
cell
types
implicated
disorders,
which
holds
great
potential
reveal
novel
interventions
targeting
PRMTs,
thus
presenting
promising
perspectives
effectively
address
substantial
global
burden
imposed
by
CVDs
disorders.
