Annals of Allergy Asthma & Immunology,
Journal Year:
2024,
Volume and Issue:
133(1), P. 33 - 42
Published: March 14, 2024
IgE
signaling
through
its
high-affinity
receptor
FcεRI
is
central
to
the
pathogenesis
of
numerous
allergic
disorders.
Oral
inhibitors
Bruton's
tyrosine
kinase
(BTKis),
which
are
currently
FDA-approved
for
treatment
B
cell
malignancies,
broadly
inhibit
pathway
in
human
mast
cells
and
basophils
therefore
may
be
effective
allergen-independent
therapies
a
variety
diseases.
The
application
these
drugs
allergy
space
was
previously
limited
by
low
selectivity
subsequent
toxicities
early-generation
compounds.
Fortunately,
next-generation,
highly-selective
BTKis
clinical
development
appear
have
more
favorable
risk-benefit
profiles,
their
likelihood
being
an
indication
increasing.
Recent
trials
demonstrated
remarkable
rapid
efficacy
second-generation
BTKi
acalabrutinib
preventing
reactivity
peanut
ingestion
peanut-allergic
adults.
Additionally,
next-generation
including
remibrutinib
effectively
reduce
disease
activity
patients
with
antihistamine-refractory
chronic
spontaneous
urticaria.
Finally,
several
under
investigation
early
atopic
dermatitis
asthma.
In
this
review,
we
summarize
recent
data
supporting
use
as
novel
food
allergy,
anaphylaxis,
urticaria,
other
We
also
discuss
safety
derived
from
utilizing
both
short-term
dosing
BTKis.
Molecular Medicine Reports,
Journal Year:
2025,
Volume and Issue:
31(3)
Published: Jan. 23, 2025
Insulin
receptor
(IR)
tyrosine
kinase
substrate
(IRTKS)
was
first
identified
>20
years
ago
as
a
tyrosine‑phosphorylated
IR
and
subsequently
characterized
protein
containing
an
inverse‑Bin‑amphiphysin‑Rvs
domain.
Subsequent
research
has
shown
that
IRTKS
functions
scaffold
with
multiple
domains,
which
results
in
diverse
variety
of
cell
activities.
For
example,
plays
roles
regulating
the
formation
membrane
protrusions;
triggering
pathogen‑driven
actin
assembly;
modulating
insulin
signaling,
antiviral
immunity
embryonic
development;
promoting
tumor
occurrence
progression.
It
is
also
candidate
forensic
biomarker
hypothermia.
Nevertheless,
systematic
summary
biological
its
underlying
molecular
mechanism
lacking.
Therefore,
present
review
provides
comprehensive
latest
advancements
research,
thereby
establishing
framework
for
understanding
contribution
to
processes.
ACS Pharmacology & Translational Science,
Journal Year:
2025,
Volume and Issue:
8(4), P. 917 - 931
Published: March 12, 2025
Uncovering
a
drug's
mechanism
of
action
and
possible
adverse
effects
are
critical
components
in
drug
discovery
development.
Moreover,
it
provides
evidence
for
why
some
drugs
prove
more
effective
than
others
how
to
design
better
altogether.
Here,
we
demonstrate
the
utility
high-throughput
vitro
screening
platform
along
with
comprehensive
panel
aid
characterization
15
Bruton's
tyrosine
kinase
(BTK)
inhibitors
that
either
approved
by
FDA
or
presently
under
clinical
evaluation.
To
compare
potency
these
drugs,
measured
binding
affinity
each
wild-type
BTK
as
well
clinically
relevant
resistance
mutant
(BTK
C481S).
In
doing
so,
discovered
considerable
difference
selectivity
proteins.
Some
this
potentially
contributes
experienced
patients
undergoing
therapy
using
drugs.
Overall,
noncovalent
showed
stronger
both
when
compared
covalent
inhibitors,
majority
demonstrating
higher
specificity
less
off-target
modulation.
Additionally,
biological
outcomes
four
human
cell-based
models.
As
expected,
found
different
phenotypic
profiles
inhibitor.
However,
two
had
fewer
inhibitors.
This
similar
in-depth
preclinical
candidates
can
provide
insights
into
efficacy
compound
may
affect
its
safety
setting.
Cureus,
Journal Year:
2025,
Volume and Issue:
unknown
Published: April 9, 2025
The
objective
of
this
paper
is
to
report
a
case
anti-myelin-associated
glycoprotein
(anti-MAG)
antibody
neuropathy
treated
with
zanubrutinib,
offering
insight
into
potential
therapeutic
avenue
for
challenging
neurological
disorder.
A
65-year-old
male
initially
presented
peripheral
in
the
lower
distal
extremities.
Hematologic
evaluation
revealed
an
elevated
M-spike
IgM
and
high
MAG
titer.
His
initial
titer
was
measured
at
1:102400
on
February
28,
2023.
These
findings
were
consistent
diagnosis
Waldenström
macroglobulinemia
(WM)
associated
anti-MAG
neuropathy.
patient
started
rituximab
reported
slight
improvement
symptoms.
However,
felt
efficacy
diminished
each
subsequent
dose.
Due
this,
initiated
zanubrutinib.
Close
monitoring
clinical
symptoms
laboratory
parameters
conducted
assess
treatment
response
side
effects.
Following
zanubrutinib
therapy,
exhibited
mild
neuropathic
symptoms,
which
have
stabilized,
although
still
present.
Serologic
examination
demonstrated
decrease
anti-MAG-antibody
1:25600
spring
2023
1:51200
November
Patient
reports
increased
fatigue
musculoskeletal
pain.
This
vignette
highlights
outcomes
management
WM.
Further
research
larger
trials
are
warranted
validate
these
establish
as
viable
option
rare
often
Kinases and Phosphatases,
Journal Year:
2025,
Volume and Issue:
3(2), P. 10 - 10
Published: May 7, 2025
Bruton’s
tyrosine
kinase
(BTK)
is
a
key
signaling
molecule
involved
in
both
hematological
malignancies
and
solid
tumors.
In
B-cell
such
as
chronic
lymphocytic
leukemia
(CLL)
non-Hodgkin
lymphoma
(NHL),
BTK
mediates
receptor
signaling,
promoting
tumor
survival
proliferation,
leading
to
the
development
of
inhibitors
like
ibrutinib
that
improve
patient
outcomes.
tumors,
isoforms,
particularly
p65BTK,
contribute
growth
therapy
resistance,
with
inhibition
showing
promise
cancers
colorectal,
ovarian,
non-small
cell
lung
cancer.
also
influences
microenvironment
by
modulating
immune
cells
myeloid-derived
suppressor
tumor-associated
macrophages,
aiding
evasion.
can
enhance
anti-tumor
immunity
reduce
inflammation-driven
progression.
Additionally,
contributes
angiogenesis,
anti-angiogenic
effects.
Beyond
cancer,
linked
aging,
where
its
modulation
may
senescent
accumulation
preserve
cognitive
function.
This
review
explores
BTK’s
dual
role,
focusing
on
oncogenic
effects
potential
impact
aging
processes.
We
discuss
use
cancer
treatment
their
address
age-related
concerns,
providing
deeper
understanding
therapeutic
target
mediator
complex
relationship
between
aging.
Journal of Biomolecular Structure and Dynamics,
Journal Year:
2025,
Volume and Issue:
unknown, P. 1 - 17
Published: May 15, 2025
Kinases
are
pivotal
in
regulating
signaling
pathways,
and
their
dysregulation
is
associated
with
various
diseases,
including
cancers,
making
them
prime
therapeutic
targets.
Bruton's
Tyrosine
Kinase
(BTK)
crucial
for
B-cell
development,
BTK
inhibitors
have
proven
effective
treating
malignancies
like
Chronic
Lymphocytic
Leukemia
(CLL).
Non-covalent
offer
a
promising
approach
by
avoiding
covalent
bond
formation
the
protein.
However,
resistance
due
to
mutations
catalytic
domain
has
led
relapses
refractory
cases
CLL,
highlighting
need
deeper
understanding
of
these
mutations'
impact
on
treatment
outcomes.
This
study
investigates
effects
four
prevalent
single-point
mutations-A428D,
T474I,
C481S,
L528W-within
BTK.
Using
12.5
microseconds
molecular
dynamics
simulations
computational
drug
discovery
methods,
we
examine
how
influence
binding
affinities
interactions
non-covalent
inhibitors.
Molecular
Mechanics-Poisson-Boltzmann
Surface
Area
(MM-PBSA)
analysis
showed
that
mutant
forms
significantly
decreased
ligand
free
energies
compared
wild
types,
few
exceptions.
With
pocket
volume
solvent-accessible
surface
area
analysis,
also
show
reduce
volume,
forcing
move
out
pocket,
disrupting
critical
confirms
experimental
clinical
observations
why
impair
inhibitor
efficacy
fostering
resistance.
Our
results
vital
insights
designing
next-generation
overcome
enhance
outcomes
malignancies.
