Pharmacological Research,
Год журнала:
2023,
Номер
194, С. 106847 - 106847
Опубликована: Июль 15, 2023
Owing
to
genetic
alterations
and
overexpression,
the
dysregulation
of
protein
kinases
plays
a
significant
role
in
pathogenesis
many
autoimmune
neoplastic
disorders
kinase
antagonists
have
become
an
important
drug
target.
Although
efficacy
imatinib
treatment
chronic
myelogenous
leukemia
United
States
2001
was
main
driver
inhibitor
discovery,
this
preceded
by
approval
fasudil
(a
ROCK
antagonist)
Japan
1995
for
cerebral
vasospasm.
There
are
21
small
molecule
inhibitors
that
approved
China,
Japan,
Europe,
South
Korea
not
Sates
75
FDA-approved
States.
Of
agents,
eleven
target
receptor
protein-tyrosine
kinases,
eight
inhibit
nonreceptor
two
block
protein-serine/threonine
kinases.
All
drugs
orally
bioavailable
or
topically
effective.
non-FDA
drugs,
sixteen
prescribed
diseases,
three
directed
toward
inflammatory
disorders,
one
is
used
glaucoma,
management
The
leading
targets
both
international
regulatory
agencies
FDA
members
EGFR
family,
VEGFR
JAK
family.
One-third
internationally
compliant
with
Lipinski's
rule
five
drugs.
relies
on
four
parameters
including
molecular
weight,
number
hydrogen
bond
donors
acceptors,
Log
partition
coefficient.
Journal of Medicinal Chemistry,
Год журнала:
2021,
Номер
65(2), С. 1047 - 1131
Опубликована: Окт. 8, 2021
The
central
role
of
dysregulated
kinase
activity
in
the
etiology
progressive
disorders,
including
cancer,
has
fostered
incremental
efforts
on
drug
discovery
programs
over
past
40
years.
As
a
result,
inhibitors
are
today
one
most
important
classes
drugs.
FDA
approved
73
small
molecule
inhibitor
drugs
until
September
2021,
and
additional
were
by
other
regulatory
agencies
during
that
time.
To
complement
published
literature
clinical
inhibitors,
we
have
prepared
review
recaps
this
large
data
set
into
an
accessible
format
for
medicinal
chemistry
community.
Along
with
therapeutic
pharmacological
properties
each
across
world
2020,
provide
synthesis
routes
originally
used
phase,
many
which
only
available
patent
applications.
In
last
section,
also
update
2021.
Compared
with
traditional
therapies,
targeted
therapy
has
merits
in
selectivity,
efficacy,
and
tolerability.
Small
molecule
inhibitors
are
one
of
the
primary
therapies
for
cancer.
Due
to
their
advantages
a
wide
range
targets,
convenient
medication,
ability
penetrate
into
central
nervous
system,
many
efforts
have
been
devoted
developing
more
small
inhibitors.
To
date,
88
approved
by
United
States
Food
Drug
Administration
treat
cancers.
Despite
remarkable
progress,
cancer
treatment
still
face
obstacles,
such
as
low
response
rate,
short
duration
response,
toxicity,
biomarkers,
resistance.
better
promote
development
targeting
cancers,
we
comprehensively
reviewed
involved
all
agents
pivotal
drug
candidates
clinical
trials
arranged
signaling
pathways
classification
We
discussed
lessons
learned
from
these
agents,
proper
strategies
overcome
resistance
arising
different
mechanisms,
combination
concerned
Through
our
review,
hoped
provide
insights
perspectives
research
treatment.
Journal of Hematology & Oncology,
Год журнала:
2022,
Номер
15(1)
Опубликована: Окт. 1, 2022
Bruton's
tyrosine
kinase
(BTK)
is
an
essential
component
of
multiple
signaling
pathways
that
regulate
B
cell
and
myeloid
proliferation,
survival,
functions,
making
it
a
promising
therapeutic
target
for
various
malignancies
inflammatory
diseases.
Five
small
molecule
inhibitors
have
shown
remarkable
efficacy
been
approved
to
treat
different
types
hematological
cancers,
including
ibrutinib,
acalabrutinib,
zanubrutinib,
tirabrutinib,
orelabrutinib.
The
first-in-class
agent,
has
created
new
era
chemotherapy-free
treatment
malignancies.
Ibrutinib
so
popular
became
the
fourth
top-selling
cancer
drug
worldwide
in
2021.
To
reduce
off-target
effects
overcome
acquired
resistance
significant
efforts
made
developing
highly
selective
second-
third-generation
BTK
combination
approaches.
Over
past
few
years,
also
repurposed
Promising
data
obtained
from
preclinical
early-phase
clinical
studies.
In
this
review,
we
summarized
current
progress
applying
disorders,
highlighting
available
results
Molecules,
Год журнала:
2023,
Номер
28(5), С. 2400 - 2400
Опубликована: Март 6, 2023
In
the
last
few
decades,
there
has
been
a
growing
interest
in
Bruton’s
tyrosine
kinase
(BTK)
and
compounds
that
target
it.
BTK
is
downstream
mediator
of
B-cell
receptor
(BCR)
signaling
pathway
affects
proliferation
differentiation.
Evidence
demonstrating
expression
on
majority
hematological
cells
led
to
hypothesis
inhibitors
(BTKIs)
such
as
ibrutinib
can
be
an
effective
treatment
for
leukemias
lymphomas.
However,
body
experimental
clinical
data
demonstrated
significance
BTK,
not
just
malignancies,
but
also
solid
tumors,
breast,
ovarian,
colorectal,
prostate
cancers.
addition,
enhanced
activity
correlated
with
autoimmune
disease.
This
gave
rise
beneficial
therapy
rheumatoid
arthritis
(RA),
systemic
lupus
erythematosus
(SLE),
multiple
sclerosis
(MS),
Sjögren’s
syndrome
(SS),
allergies,
asthma.
this
review
article,
we
summarize
most
recent
findings
regarding
well
advanced
have
developed
date
their
applications
mainly
cancer
chronic
inflammatory
disease
patients.
Science,
Год журнала:
2022,
Номер
377(6608), С. 875 - 880
Опубликована: Авг. 19, 2022
The
B
cell
receptor
(BCR)
initiates
immune
responses
through
antigen
recognition.
We
report
a
3.3-angstrom
cryo-electron
microscopy
structure
of
human
immunoglobulin
M
(IgM)-BCR
in
the
resting
state.
IgM-BCR
comprises
two
heavy
chains,
light
and
Igα/Igβ
heterodimer.
ectodomains
chains
closely
stack
against
those
Igα/Igβ,
with
one
chain
locked
between
Igα
Igβ
juxtamembrane
region.
Extracellular
interactions
may
determine
isotype
specificity
BCR.
transmembrane
helices
form
four-helix
bundle
that
appears
to
be
conserved
among
all
BCR
isotypes.
This
contains
14
glycosylation
sites
on
reveals
three
potential
surface
binding
sites.
Our
work
organizational
principles
facilitate
design
antibody-based
therapeutics.
Cancers,
Год журнала:
2022,
Номер
14(3), С. 771 - 771
Опубликована: Фев. 2, 2022
The
use
of
Bruton’s
tyrosine
kinase
(BTK)
inhibitors
has
changed
the
management
and
clinical
history
patients
with
chronic
lymphocytic
leukemia
(CLL).
BTK
is
a
critical
molecule
that
interconnects
B-cell
antigen
receptor
(BCR)
signaling.
BTKis
are
classified
into
two
categories:
irreversible
(covalent)
reversible
(non-covalent)
inhibitors.
Ibrutinib
was
first
inhibitor
approved
by
U.S.
Food
Drug
Administration
in
2013
as
breakthrough
therapy
CLL
patients.
Subsequently,
several
studies
have
evaluated
efficacy
safety
new
agents
reduced
toxicity
when
compared
ibrutinib.
Two
other
irreversible,
second-generation
inhibitors,
acalabrutinib
zanubrutinib,
were
developed
to
reduce
ibrutinib-mediated
adverse
effects.
Additionally,
currently
under
development
early-phase
improve
their
activity
diminish
This
review
summarizes
pharmacology,
efficacy,
safety,
dosing,
drug–drug
interactions
associated
treatment
examines
further
implications.
Journal of Clinical Medicine,
Год журнала:
2022,
Номер
11(10), С. 2807 - 2807
Опубликована: Май 16, 2022
The
use
of
Bruton’s
tyrosine
kinase
(BTK)
inhibitors
has
changed
the
management
patients
with
B-cell
lymphoid
malignancies.
BTK
is
an
important
molecule
that
interconnects
antigen
receptor
(BCR)
signaling.
(BTKis)
are
classified
into
three
categories,
namely
covalent
irreversible
inhibitors,
reversible
and
non-covalent
inhibitors.
Ibrutinib
first
covalent,
inhibitor
approved
in
2013
as
a
breakthrough
therapy
for
chronic
lymphocytic
leukemia
patients.
Subsequently,
two
other
irreversible,
second-generation
BTKis,
acalabrutinib
zanubrutinib,
have
been
developed
malignancies
to
reduce
ibrutinib-mediated
adverse
effects.
More
recently,
BTKis
under
development
immune-mediated
diseases,
including
autoimmune
hemolytic
anemia,
immune
thrombocytopenia,
multiple
sclerosis,
pemphigus
vulgaris,
atopic
dermatitis,
rheumatoid
arthritis,
systemic
lupus
erythematosus,
Sjögren’s
disease,
spontaneous
urticaria,
among
others.
This
review
article
summarizes
preclinical
clinical
evidence
supporting
role
various
autoimmune,
allergic,
inflammatory
conditions.
Journal of Hematology & Oncology,
Год журнала:
2022,
Номер
15(1)
Опубликована: Сен. 29, 2022
Abstract
Primary
central
nervous
system
lymphoma
(PCNSL)
is
a
type
of
restricted
non-Hodgkin
lymphoma,
whose
histopathological
diagnosis
majorly
large
B
cell
lymphoma.
To
provide
specific,
evidence-based
recommendations
for
medical
professionals
and
to
promote
more
standardized,
effective
safe
treatment
patients
with
PCNSL,
panel
experts
from
the
Chinese
Neurosurgical
Society
Medical
Association
Hematological
Malignancies
Anti-Cancer
jointly
developed
an
consensus.
After
comprehensively
searching
literature
conducting
systematic
reviews,
two
rounds
Delphi
were
conducted
reach
consensus
on
as
follows:
The
specimens
PCNSL
should
be
obtained
safely
possible
by
multimodal
tomography-guided
biopsy
or
minimally
invasive
surgery.
Corticosteroids
withdrawn
from,
not
administered
to,
suspected
before
if
patient’s
status
permits.
MRI
(enhanced
DWI)
performed
diagnosing
evaluating
where
whole-body
PET-CT
used
at
necessary
time
points.
Mini-mental
examination
can
assess
cognitive
function
in
clinical
management.
Newly
diagnosed
treated
combined
high-dose
methotrexate-based
regimen
rituximab-inclusive
induction
therapy.
Autologous
stem
transplantation
consolidation
Refractory
relapsed
ibrutinib
without
chemotherapy
re-induction
Stereotactic
radiosurgery
limited
recurrent
lesion
who
refractory
have
previously
received
whole-brain
radiotherapy.
Patients
primary
vitreoretinal
(PVRL)
vitreous
biopsy.
PVRL
concurrent
VRL
systemic
local
Cancers,
Год журнала:
2023,
Номер
15(5), С. 1504 - 1504
Опубликована: Фев. 27, 2023
Ibrutinib
revolutionized
the
CLL
treatment
approach
and
prognosis
demonstrating
its
efficacy
safety
even
at
extended
follow-up.
During
last
few
years,
several
next-generation
inhibitors
have
been
developed
to
overcome
occurrence
of
toxicity
or
resistance
in
patients
on
continuous
treatment.
In
a
head-to-head
comparison
two
phase
III
trials,
both
acalabrutinib
zanubrutinib
demonstrated
lower
incidence
adverse
events
respect
ibrutinib.
Nevertheless,
mutations
remain
concern
with
therapy
were
first-
covalent
inhibitors.
Reversible
showed
independently
previous
presence
BTK
mutations.
Other
strategies
are
currently
under
development
CLL,
especially
for
high-risk
patients,
include
inhibitor
combinations
BCl2
without
anti-CD20
monoclonal
antibodies.
Finally,
new
mechanisms
inhibition
investigations
progressing
non-covalent
Here
we
summarize
discuss
results
from
main
experiences
irreversible
reversable
CLL.
