Design, Synthesis and Biological Evaluation of Novel 9H Purine Derivatives as Potent CDK9 Inhibitors
Chemical Biology & Drug Design,
Год журнала:
2025,
Номер
105(2)
Опубликована: Янв. 30, 2025
ABSTRACT
Cyclin‐dependent
kinase
9
(CDK9)
is
considered
as
an
important
target
in
the
research
of
antitumor
drugs.
Taking
CDK2/9
inhibitor
CYC065
positive
control
and
in‐house
library
compound
(
64
)
lead
compound,
four
classes
22
compounds
with
9H
purine
core
structure
were
designed
to
establish
structure–activity
relationships
(SAR).
In
general,
SAR
CDK9
inhibitors
systematically
described
this
paper,
resulting
discovery
two
B2
B5
further
value.
After
conducting
selectivity
testing
against
kinase,
demonstrated
approximately
five‐fold
greater
towards
CDK9‐cyclinT1
over
CDK2‐cyclinE2.
This
work
also
provides
a
reference
basis
for
subsequent
on
inhibitors.
Язык: Английский
Advances in the Design, Discovery, and optimization of aurora kinase inhibitors as anticancer agents
Expert Opinion on Drug Discovery,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 17, 2025
Introduction
Aurora
kinases
(AKs)
play
key
roles
during
carcinogenesis
and
show
a
close
relationship
with
many
cellular
effects
including
mitotic
entry,
spindle
assembly
chromosomal
alignment
biorientation.
Indeed,
elevated
levels
of
AKs
have
been
reported
in
several
different
tumor
types,
leading
research
scientists
to
investigate
ways
that
we
can
target
for
the
purpose
developing
new
anticancer
therapeutics.
Язык: Английский
Drug repurposing of cyclin-dependent kinase inhibitors for neutrophilic acute respiratory distress syndrome and psoriasis
Journal of Advanced Research,
Год журнала:
2024,
Номер
unknown
Опубликована: Июль 1, 2024
Neutrophilic
inflammation,
characterized
by
dysregulated
neutrophil
activation,
triggers
a
variety
of
inflammatory
responses
such
as
chemotactic
infiltration,
oxidative
bursts,
degranulation,
extracellular
traps
(NETs)
formation,
and
delayed
turnover.
This
type
inflammation
is
pivotal
in
the
pathogenesis
acute
respiratory
distress
syndrome
(ARDS)
psoriasis.
Despite
current
treatments,
managing
neutrophil-associated
symptoms
remains
significant
challenge.
review
emphasizes
role
cyclin-dependent
kinases
(CDKs)
activation
inflammation.
It
aims
to
highlight
therapeutic
potential
repurposing
CDK
inhibitors
manage
neutrophilic
particularly
ARDS
Additionally,
it
discusses
necessary
precautions
for
clinical
application
these
due
off-target
effects
need
dose
optimization.
CDKs
regulate
key
functions,
including
responses,
NET
apoptosis.
Repurposing
inhibitors,
originally
developed
cancer
treatment,
shows
promise
controlling
Clinical
anticancer
drugs,
palbociclib
ribociclib,
have
demonstrated
efficacy
treating
psoriasis
targeting
off-label
pathways,
phosphoinositide
3-kinase
(PI3K)
phosphodiesterase
4
(PDE4),
respectively.
While
offer
promising
benefits,
their
requires
careful
consideration
Further
exploration
trials
are
ensure
safety
conditions.
Язык: Английский
Advances in Cancer Therapy: A Comprehensive Review of CDK and EGFR Inhibitors
Cells,
Год журнала:
2024,
Номер
13(19), С. 1656 - 1656
Опубликована: Окт. 6, 2024
Protein
kinases
have
essential
responsibilities
in
controlling
several
cellular
processes,
and
their
abnormal
regulation
is
strongly
related
to
the
development
of
cancer.
The
implementation
protein
kinase
inhibitors
has
significantly
transformed
cancer
therapy
by
modifying
treatment
strategies.
These
received
substantial
FDA
clearance
recent
decades.
emerged
as
primary
objectives
for
therapeutic
interventions,
particularly
context
treatment.
At
present,
69
therapeutics
been
approved
that
target
approximately
24
kinases,
which
are
specifically
prescribed
neoplastic
illnesses.
novel
agents
inhibit
certain
such
receptor
protein-tyrosine
protein-serine/threonine
dual-specificity
nonreceptor
kinases.
This
review
presents
a
comprehensive
overview
targets
inhibitors,
with
specific
focus
on
cyclin-dependent
(CDKs)
epidermal
growth
factor
(EGFR).
majority
reviewed
studies
commenced
an
assessment
cell
lines
concluded
biological
evaluation
individual
targets.
articles
provide
detailed
information
structural
features
potent
anticancer
activity,
refers
ability
selectively
cancer-promoting
including
CDKs
EGFR.
Additionally,
latest
FDA-approved
targeting
these
enzymes
were
highlighted
accordingly.
Язык: Английский
Discovery of novel pyrrolo[2,3-d]pyrimidine derivatives as anticancer agents: virtual screening and molecular dynamic studies
SAR and QSAR in environmental research,
Год журнала:
2024,
Номер
unknown, С. 1 - 33
Опубликована: Ноя. 28, 2024
CDK/Cyclins
are
dysregulated
in
several
human
cancers.
Recent
studies
showed
inhibition
of
CDK4/6
was
responsible
for
controlling
cell
cycle
progression
and
cancer
growth.
In
the
present
study,
atom-based
field-based
3D-QSAR,
virtual
screening,
molecular
docking
dynamics
were
done
development
novel
pyrrolo[2,3-d]pyrimidine
(P2P)
derivatives
as
anticancer
agents.
The
developed
models
good
Язык: Английский