Dermatology and Therapy,
Год журнала:
2024,
Номер
14(11), С. 3113 - 3132
Опубликована: Ноя. 1, 2024
Difamilast
has
proven
to
be
an
effective
treatment
for
the
of
atopic
dermatitis
(AD)
in
Japan,
but
its
cost-effectiveness
remains
unknown.
Therefore,
objective
current
study
was
determine
difamilast
1%
compared
with
delgocitinib
0.5%
Japanese
adult
patients
moderate-to-severe
AD
and
placebo
all-severity
from
a
public
health-care
perspective.
The
analysis
conducted
using
model
This
had
four
health
states
("clear,"
"mild,"
"moderate,"
"severe")
defined
according
Eczema
Area
Severity
Index
score.
time
horizon
1
year.
Because
period
short,
no
discount
rate
applied.
proportions
previously
estimated
by
anchored
matching-adjusted
indirect
comparison
were
implemented
model.
further
populated
data
literature.
main
outcomes
quality-adjusted
life-years
(QALY),
costs,
outcomes,
including
incremental
ratio.
All
prices
stated
JPY
at
price
level
2018
April
2019
March.
One-way
sensitivity
probabilistic
(PSA)
performed
assess
robustness
results.
In
base
case,
827,054/QALY
1,518,657/QALY,
respectively.
PSA
showed
that
66.6%
99.6%
probability
being
below
5
million/QALY
threshold,
results
suggest
is
more
cost-effective
option
Signal Transduction and Targeted Therapy,
Год журнала:
2023,
Номер
8(1)
Опубликована: Ноя. 27, 2023
Abstract
Psoriasis
is
a
common,
chronic,
and
inflammatory
skin
disease
with
high
burden
on
individuals,
health
systems,
society
worldwide.
With
the
immunological
pathologies
pathogenesis
of
psoriasis
becoming
gradually
revealed,
therapeutic
approaches
for
this
have
gained
revolutionary
progress.
Nevertheless,
mechanisms
less
common
forms
remain
elusive.
Furthermore,
severe
adverse
effects
recurrence
upon
treatment
cessation
should
be
noted
addressed
during
treatment,
which,
however,
has
been
rarely
explored
integration
preliminary
findings.
Therefore,
it
crucial
to
comprehensive
understanding
behind
pathogenesis,
which
might
offer
new
insights
research
lead
more
substantive
progress
in
expand
clinical
options
treatment.
In
review,
we
looked
briefly
introduce
epidemiology,
subtypes,
pathophysiology,
comorbidities
systematically
discuss
signaling
pathways
involving
extracellular
cytokines
intracellular
transmission,
as
well
cross-talk
between
them.
discussion,
also
paid
attention
potential
metabolic
epigenetic
molecular
mechanistic
cascades
related
its
comorbidities.
This
review
outlined
current
psoriasis,
especially
targeted
therapies
novel
strategies,
mechanism
recurrence.
International Journal of COPD,
Год журнала:
2023,
Номер
Volume 18, С. 1333 - 1352
Опубликована: Июнь 1, 2023
Airway
inflammation,
driven
by
different
types
of
inflammatory
cells
and
mediators,
plays
a
fundamental
role
in
COPD
its
progression.
Neutrophils,
eosinophils,
macrophages,
CD4
Journal of Medicinal Chemistry,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 23, 2025
Pulmonary
inflammation
is
the
main
cause
of
lung
injury.
Phosphodiesterase
4
(PDE4)
a
promising
anti-inflammatory
target
for
treatment
respiratory
diseases.
Herein,
we
designed
and
synthesized
43
compounds
in
two
novel
series
benzimidazole
derivatives
as
PDE4
inhibitors.
Among
them,
compound
A5
showed
highly
selective
inhibition
PDE4,
good
safety,
liver
microsomal
stability
vitro.
administration
remarkably
attenuated
inflammatory
infiltration
pathologic
injury
models
acute
mice
chronic
obstructive
pulmonary
disease
(COPD)
mice.
In
addition,
enhanced
sputum
secretion,
relieved
cough
mice,
inhibited
phosphorylation
p38
MAP
kinase,
an
important
protein
regulation
Overall,
A5,
effective
inhibitor
without
toxicity
gastrointestinal
reaction,
may
be
potent
candidate
Biomedicine & Pharmacotherapy,
Год журнала:
2024,
Номер
177, С. 117009 - 117009
Опубликована: Июнь 21, 2024
Cyclic
adenosine
monophosphate
(cAMP)
is
a
key
second
messenger
that
regulates
signal
transduction
pathways
pivotal
for
numerous
biological
functions.
Intracellular
cAMP
levels
are
spatiotemporally
regulated
by
their
hydrolyzing
enzymes
called
phosphodiesterases
(PDEs).
It
has
been
shown
increased
in
the
central
nervous
system
(CNS)
promote
neuroplasticity,
neurotransmission,
neuronal
survival,
and
myelination
while
suppressing
neuroinflammation.
Thus,
elevating
through
PDE
inhibition
provides
therapeutic
approach
multiple
CNS
disorders,
including
sclerosis,
stroke,
spinal
cord
injury,
amyotrophic
lateral
traumatic
brain
Alzheimer's
disease.
In
particular,
of
cAMP-specific
PDE4
subfamily
widely
studied
because
its
high
expression
CNS.
So
far,
clinical
translation
full
inhibitors
hampered
dose-limiting
side
effects.
Hence,
focusing
on
signaling
cascades
downstream
activated
upon
presents
promising
strategy,
offering
novel
pharmacologically
safe
targets
treating
disorders.
Yet,
underlying
PDE(4)
remain
partially
elusive.
This
review
comprehensive
overview
existing
knowledge
regarding
mediators
induced
or
stimulators.
Furthermore,
we
highlight
gaps
future
perspectives
may
incentivize
additional
research
concerning
inhibition,
thereby
providing
approaches
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(15), С. 8052 - 8052
Опубликована: Июль 24, 2024
Phosphodiesterase
4
(PDE4)
enzymes
catalyze
cyclic
adenosine
monophosphate
(cAMP)
hydrolysis
and
are
involved
in
a
variety
of
physiological
processes,
including
brain
function,
monocyte
macrophage
activation,
neutrophil
infiltration.
Among
different
PDE4
isoforms,
Phosphodiesterases
4D
(PDE4Ds)
play
fundamental
role
cognitive,
learning
memory
consolidation
processes
cancer
development.
Selective
PDE4D
inhibitors
(PDE4Dis)
could
represent
an
innovative
valid
therapeutic
strategy
for
the
treatment
various
neurodegenerative
diseases,
such
as
Alzheimer’s,
Parkinson’s,
Huntington’s,
Lou
Gehrig’s
but
also
stroke,
traumatic
spinal
cord
injury,
mild
cognitive
impairment,
all
demyelinating
diseases
multiple
sclerosis.
In
addition,
small
molecules
able
to
block
isoforms
have
been
recently
studied
specific
types,
particularly
hepatocellular
carcinoma
breast
cancer.
This
review
overviews
PDE4DIsso
far
identified
provides
useful
information,
from
medicinal
chemistry
point
view,
development
novel
series
compounds
with
improved
pharmacological
properties.
Frontiers in Bioscience-Landmark,
Год журнала:
2023,
Номер
28(7), С. 133 - 133
Опубликована: Июль 4, 2023
The
second
messenger,
cyclic
adenosine
monophosphate
(cAMP),
is
a
master
regulator
of
signal
transduction
that
maintains
cell
homeostasis.
A
fine
balance
between
cAMP
synthesis
by
adenylyl
cyclase
and
degradation
phosphodiesterases
(PDEs)
underpins
receptor-specific
responses.
As
multiple
receptors
rely
on
for
signaling,
PDEs
shape
three-dimensional,
localized
gradients
the
nucleotide
to
drive
appropriate
signaling
cascades.
Of
11
PDE
families,
PDE4,
which
comprises
long,
short,
supershort
isoforms
dead-short
isoform,
great
interest
due
its
implication
in
disease.
Aberrant
PDE4
expression
post-translational
modifications
are
hallmarks
several
clinical
indications
curative
treatment
not
yet
available.
While
some
PDE4-specific
small
molecule
inhibitors
directed
against
active
site
approved
use,
they
limited
severe
side
effects
owing
high
degree
conservation
catalytic
domain
over
20
unique
isoforms.
Some
attempts
use
different
modular
structure
exists
long
shorter
now
bearing
success.
However,
these
exclusively
aimed
at
isoforms,
have
been
focus
majority
research
this
area.
Here,
we
summarised
literature
lesser-studied
short
provide
record
discovery,
regulation,
disease
relevance
class
enzymes
represent
an
untapped
target
specific
inhibition
future.
Antibodies,
Год журнала:
2024,
Номер
13(3), С. 76 - 76
Опубликована: Сен. 14, 2024
Psoriasis
is
a
persistent,
inflammatory
condition
affecting
millions
globally,
marked
by
excessive
keratinocyte
proliferation,
immune
cell
infiltration,
and
widespread
inflammation.
Over
the
years,
therapeutic
approaches
have
developed
significantly,
shifting
from
conventional
topical
treatments
phototherapy
to
more
sophisticated
systemic
interventions
such
as
biologics
and,
recently,
oral
small-molecule
drugs.
This
review
seeks
present
comprehensive
investigation
of
existing
psoriasis
treatment
options,
focusing
on
biologic
agents,
small
molecules,
emerging
treatments.
Several
categories
received
regulatory
approval
for
psoriasis,
including
TNF-α,
IL-17,
IL-12/23,
IL-23
inhibitors.
Biologics
revolutionized
psoriasis.
These
targeted
therapies
offer
significant
improvement
in
disease
control
quality
life,
with
acceptable
safety
profiles.
However,
limitations
cost,
potential
immunogenicity,
administration
challenges
driven
exploration
alternative
modalities.
Oral
particularly
inhibitors
Janus
kinase
(JAK),
emerged
options
due
their
convenience
efficacy.
agents
represent
paradigm
shift
management
condition,
offering
action
specific
signaling
pathways.
In
addition
therapies,
explores
that
hold
promise
future
care.
include
innovative
Early-stage
clinical
trials
suggest
these
may
enhance
outcomes
patients.
conclusion,
landscape
rapidly
evolving,
emphasizing
targeted,
patient-centered
Ongoing
research
development
are
expected
lead
personalized
effective
strategies
this
complex
condition.
