Properties of FDA-approved small molecule protein kinase inhibitors: A 2024 update
Pharmacological Research,
Год журнала:
2024,
Номер
200, С. 107059 - 107059
Опубликована: Янв. 11, 2024
Owing
to
the
dysregulation
of
protein
kinase
activity
in
many
diseases
including
cancer,
this
enzyme
family
has
become
one
most
important
drug
targets
21st
century.
There
are
80
FDA-approved
therapeutic
agents
that
target
about
two
dozen
different
kinases
and
seven
these
drugs
were
approved
2023.
Of
drugs,
thirteen
protein-serine/threonine
kinases,
four
directed
against
dual
specificity
(MEK1/2),
twenty
block
nonreceptor
protein-tyrosine
43
inhibit
receptor
kinases.
The
data
indicate
69
prescribed
for
treatment
neoplasms.
Six
(abrocitinib,
baricitinib,
deucravacitinib,
ritlecitinib,
tofacitinib,
upadacitinib)
used
inflammatory
(atopic
dermatitis,
rheumatoid
arthritis,
psoriasis,
alopecia
areata,
ulcerative
colitis).
nearly
multiple
diseases.
following
received
FDA
approval
2023:
capivasertib
(HER2-positive
breast
cancer),
fruquintinib
(metastatic
colorectal
momelotinib
(myelofibrosis),
pirtobrutinib
(mantle
cell
lymphoma,
chronic
lymphocytic
leukemia,
small
lymphoma),
quizartinib
(Flt3-mutant
acute
myelogenous
leukemia),
repotrectinib
(ROS1-positive
lung
ritlecitinib
(alopecia
areata).
All
orally
effective
with
exception
netarsudil,
temsirolimus,
trilaciclib.
This
review
summarizes
physicochemical
properties
all
molecule
inhibitors
molecular
weight,
number
hydrogen
bond
donors/acceptors,
polar
surface
area,
potency,
solubility,
lipophilic
efficiency,
ligand
efficiency.
Язык: Английский
Pyrimidine scaffold dual‐target kinase inhibitors for cancer diseases: A review on design strategies, synthetic approaches, and structure–activity relationship (2018‒2023)
Archiv der Pharmazie,
Год журнала:
2025,
Номер
358(1)
Опубликована: Янв. 1, 2025
Abstract
Cancer,
the
second
leading
cause
of
death
globally,
causes
a
significant
threat
to
life.
Despite
advancements
in
treatment
cancer,
persistent
challenges
include
severe
side
effects
and
emergence
acquired
drug
resistance.
Additionally,
many
traditional
chemotherapy
drugs
show
restricted
efficacy
high
toxicity,
primarily
attributed
their
lack
selectivity.
Thus,
development
targeting
protein
kinases
has
emerged
as
noteworthy
priority
for
addressing
human
cancers.
Medicinal
chemists
have
shown
considerable
interest
dual
candidates
strategy
create
medicines
that
are
safer,
more
efficient,
cost‐effective.
Furthermore,
Food
Drug
Administration
(FDA)
approved
several
dual‐target
anticancer
treatment,
emphasizing
lower
risks
interactions
improved
pharmacokinetics
safety
profiles.
This
review
focuses
on
synthetic
efforts,
design
strategies,
structure–activity
relationship
pyrimidine
scaffold‐based
kinase
inhibitors
developed
with
potential
within
recent
6
years
(2018‒2023).
Collectively,
these
strategies
expected
offer
fresh
perspectives
future
directions
pyrimidine‐based
design,
potentially
advancing
cancer
therapeutics.
Язык: Английский
Molecular biology of the novel anticancer medications: a focus on kinases inhibitors, biologics and CAR T-cell therapy
Inflammation Research,
Год журнала:
2025,
Номер
74(1)
Опубликована: Фев. 17, 2025
Язык: Английский
Effects of the fatty acid synthase inhibitors triclosan and lapatinib on dengue virus and Zika virus infection
Scientific Reports,
Год журнала:
2025,
Номер
15(1)
Опубликована: Март 28, 2025
Fatty
acid
synthase
(FASN)
has
been
shown
to
be
critical
in
the
replication
of
several
viruses
genus
Orthoflavivirus.
In
this
study
role
two
inhibitors
FASN
that
work
through
different
mechanisms
were
investigated
dengue
virus
(DENV)
and
Zika
(ZIKV)
infections.
Triclosan
is
a
inhibitor
targets
enol
reductase
domain
FASN,
while
lapatinib
exerts
an
effect
on
acting
HER2,
upstream
regulator
FASN.
After
determining
cytotoxicity,
comprehensive
analysis
these
drugs
DENV
2
ZIKV
infection
was
undertaken.
The
results
showed
triclosan
had
moderate
antiviral
activity
against
both
(EC50
=
10.21
µM;
Selective
index
(SI)
3.99)
(
EC50
22.84
SI
5.49).
Lapatinib
reasonable
4.9
26.09),
but
computer
modeling
suggested
potential
directly
by
binding
NS5.
result
better
fit
with
NS5
than
NS5,
confirmed
as
for
towards
µM
calculated
37.92.
are
consistent
other
studies
use
target
domains
suggesting
simply
targeting
enzymatic
insufficient
therapeutic
drug
development,
lapatinib,
or
similar
molecules
may
have
real
potential.
Язык: Английский
Properties of FDA-approved small molecule protein kinase inhibitors: a 2025 update
Pharmacological Research,
Год журнала:
2025,
Номер
unknown, С. 107723 - 107723
Опубликована: Апрель 1, 2025
Because
of
the
deregulation
protein
kinase
action
in
many
inflammatory
diseases
and
cancer,
family
has
become
one
most
significant
drug
targets
21st
century.
There
are
85
FDA-approved
antagonists
that
target
about
two
dozen
different
enzymes
four
these
drugs
were
approved
2024
a
fifth
was
2025.
Of
drugs,
five
dual
specificity
kinases
(MEK1/2),
fourteen
inhibit
protein-serine/threonine
kinases,
twenty-one
block
nonreceptor
protein-tyrosine
45
receptor
kinases.
The
data
indicate
75
prescribed
for
treatment
neoplasms.
Seven
(abrocitinib,
baricitinib,
deucravacitinib,
deuruxolitinib,
ritlecitinib,
tofacitinib,
upadacitinib)
management
(atopic
dermatitis,
rheumatoid
arthritis,
psoriasis,
alopecia
areata,
ulcerative
colitis).
agents,
used
multiple
diseases.
following
received
FDA
approval
-
deuruxolitinib
(alopecia
areata),
ensartinib
lazertinib
(non-small
cell
lung
cancer),
tovorafenib
(pediatric
glioma)
while
mirdametinib
2025
type
I
neurofibromatosis
(von
Recklinghausen
disease).
Apart
from
netarsudil,
temsirolimus,
trilaciclib,
blockers
orally
bioavailable.
This
article
summarizes
physicochemical
properties
all
small
molecule
inhibitors
including
molecular
weight,
number
hydrogen
bond
donors/acceptors,
ligand
efficiency,
lipophilic
polar
surface
area,
solubility.
A
total
39
have
least
Lipinski
rule
5
violation.
Язык: Английский
Discovery of novel 4-trifluoromethyl-2-anilinoquinoline derivatives as potential anti-cancer agents targeting SGK1
Molecular Diversity,
Год журнала:
2024,
Номер
unknown
Опубликована: Авг. 9, 2024
Язык: Английский
Melt-blown polypropylene nonwoven as an efficient and eco-economic sorbent for pipette tip micro-solid phase extraction for the determination of tyrosine kinase inhibitors
Analytica Chimica Acta,
Год журнала:
2024,
Номер
1329, С. 343240 - 343240
Опубликована: Сен. 12, 2024
Язык: Английский
Potential protein kinase inhibitors that target G-quadruplex DNA structures in the human telomeric regions
Molecular Diversity,
Год журнала:
2024,
Номер
28(5), С. 3377 - 3391
Опубликована: Март 21, 2024
Язык: Английский
The Whole Proteome, Phosphoproteome, and Glycoproteome Landscape of Pan-Cancer Cell Lines Profiled by Mass Spectrometry and Reverse Phase Protein Array
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 1, 2024
Abstract
Mammalian
cancer
cell
lines
are
essential
model
systems
in
biomedical
research.
We
conducted
multi-level
proteomics
analyses
on
54
widely
used
derived
from
various
tissue-of-origins
using
two
prominent
technologies:
mass
spectrometry
(MS)
and
reverse-phase
protein
array
(RPPA).
Our
analysis
identified
10,088
proteins,
33,609
phosphorylation
sites
across
7,289
phosphoproteins,
56,350
site-specific
glycans
16,296
glycosylation
5,966
glycoproteins,
along
with
305
drug-relevant
phosphoprotein
targets.
results
reveal
both
consistent
distinct
patterns
expression
modification
between
MS
RPPA,
underscoring
their
complementary
strengths
as
discovery
tools.
Additionally,
we
features
that
distinguish
tissue
origins
different
line
lineages.
This
dataset
supports
system
selection
for
drug
target-related
studies
vitro
provides
valuable
insights
into
key
signaling
pathways.
Overall,
this
comprehensive
resource
enables
new
opportunities
exploration
biology
offers
significant
value
to
research
communities
focused
biomarker
profiling,
target
discovery,
understanding
mechanisms
diverse
types.
Язык: Английский