bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Март 30, 2023
Abstract
During
Caenorhabditis
elegans
development
multiple
cells
migrate
long
distances
or
extend
processes
to
reach
their
final
position
and/or
attain
proper
shape.
Wnt
signalling
pathway
stands
out
as
one
of
the
major
coordinators
cell
migration
outgrowth
along
anterior-posterior
body
axis.
outcome
is
fine-tuned
by
various
mechanisms
including
endocytosis.
In
this
study,
we
show
that
SEL-5,
C.
orthologue
mammalian
AP2-associated
kinase
AAK1,
acts
together
with
retromer
complex
a
positive
regulator
EGL-20/Wnt
during
QL
neuroblast
daughter
cells.
At
same
time,
SEL-5
in
cooperation
also
required
excretory
canal
outgrowth.
Importantly,
activity
not
for
its
role
either
neuronal
and
neither
these
dependent
on
DPY-23/AP2M1
phosphorylation.
We
further
establish
proteins
CWN-1
CWN-2
Frizzled
receptor
CFZ-2
positively
regulate
outgrowth,
while
LIN-44/Wnt
LIN-17/Frizzled
generate
stop
signal
inhibiting
extension.
Journal of Medicinal Chemistry,
Год журнала:
2023,
Номер
66(4), С. 2257 - 2281
Опубликована: Фев. 6, 2023
CK2
(casein
kinase
2)
is
a
serine/threonine
protein
that
ubiquitous
in
eukaryotic
cells
and
plays
important
roles
variety
of
cellular
functions,
including
cell
growth,
apoptosis,
circadian
rhythms,
DNA
damage
repair,
transcription,
translation.
involved
cancer
pathogenesis
the
occurrence
many
diseases.
Therefore,
targeting
promising
therapeutic
strategy.
Although
CK2-specific
small-molecule
inhibitors
have
been
developed,
only
CX-4945
has
progressed
to
clinical
trials.
In
recent
years,
novel
gradually
become
research
hotspot,
which
expected
overcome
limitations
traditional
inhibitors.
Herein,
we
summarize
structure,
biological
disease
relevance
emphatically
analyze
structure-activity
relationship
(SAR)
binding
modes
We
also
discuss
latest
progress
strategies,
providing
insights
into
new
drugs
for
practice.
Journal of Medicinal Chemistry,
Год журнала:
2024,
Номер
67(18), С. 15968 - 15995
Опубликована: Сен. 11, 2024
Heat
shock
protein
90
(HSP90),
a
highly
conserved
member
of
the
heat
family,
regulates
various
proteins
and
signaling
pathways
involved
in
cancer,
making
it
promising
target
for
cancer
therapy.
Traditional
HSP90
inhibitors
have
demonstrated
significant
antitumor
potential
preclinical
trials,
with
over
20
compounds
advancing
to
clinical
trials
showing
results.
However,
limited
efficacy
shared
toxicity
these
restrict
their
further
use.
Encouragingly,
developing
novel
using
conventional
medicinal
chemistry
approaches─such
as
selective
inhibitors,
dual
protein-protein
interaction
proteolysis-targeting
chimeras─is
expected
address
challenges.
Notably,
inhibitor
TAS-116
has
already
been
successfully
marketed.
In
this
Perspective,
we
summarize
structure,
biological
functions,
roles
analyze
status
highlight
latest
advancements
strategies,
offering
insights
into
future
development.
Journal of Enzyme Inhibition and Medicinal Chemistry,
Год журнала:
2023,
Номер
38(1)
Опубликована: Ноя. 13, 2023
Adaptor
associated
kinase
1
(AAK1),
a
member
of
the
Ark1/Prk1
family
Ser/Thr
kinases,
is
specific
key
regulating
Thr156
phosphorylation
at
μ2
subunit
adapter
complex-2
(AP-2)
protein.
Due
to
their
important
biological
functions,
AAK1
systems
have
been
validated
in
clinics
for
neuropathic
pain
therapy,
and
are
being
explored
as
potential
therapeutic
targets
diseases
caused
by
various
viruses
such
Hepatitis
C
(HCV),
Dengue,
Ebola,
COVID-19
amyotrophic
lateral
sclerosis
(ALS).
Centreing
on
advances
drug
discovery
programs
this
field
up
2023,
inhibitors
discussed
from
aspects
structure-based
rational
molecular
design,
pharmacology,
toxicology
synthetic
routes
compounds
interest
review.
The
aim
provide
medicinal
chemistry
community
with
up-to-date
information
accelerate
small
molecule
inhibitors.
