Journal of Medicinal Chemistry,
Journal Year:
2022,
Volume and Issue:
65(18), P. 12014 - 12030
Published: Sept. 12, 2022
Inflammatory
responses
are
important
in
cancer,
particularly
the
context
of
monocyte-rich
aggressive
myeloid
neoplasm.
We
developed
a
label-free
cellular
phenotypic
drug
discovery
assay
to
identify
anti-inflammatory
drugs
human
monocytes
derived
from
acute
leukemia
(AML),
by
tracking
several
features
ionizing
only
2500
cells
using
matrix-assisted
laser
desorption/ionization-time
flight
(MALDI-TOF)
mass
spectrometry.
A
proof-of-concept
screen
showed
that
BCR-ABL
inhibitor
nilotinib,
but
not
structurally
similar
imatinib,
blocks
inflammatory
responses.
In
order
(off-)targets
we
performed
thermal
proteome
profiling
(TPP).
Unlike
nilotinib
and
other
later-generation
inhibitors
bind
p38α
inhibit
p38α-MK2/3
signaling
axis,
which
suppressed
pro-inflammatory
cytokine
expression,
cell
adhesion,
innate
immunity
markers
activated
AML.
Thus,
our
study
provides
tool
for
new
drugs,
could
contribute
treatment
inflammation
neoplasms
diseases.
Cell Reports Methods,
Journal Year:
2024,
Volume and Issue:
4(2), P. 100717 - 100717
Published: Feb. 1, 2024
Method
development
for
mass
spectrometry
(MS)-based
thermal
shift
proteomic
assays
have
advanced
to
probe
small
molecules
with
known
and
unknown
protein-ligand
interaction
mechanisms
specificity,
which
is
predominantly
used
in
characterization
of
drug-protein
interactions.
In
the
discovery
target
off-target
interactions,
a
thorough
investigation
method
their
impact
on
sensitivity
accuracy
protein-small
molecule
protein-protein
interactions
warranted.
this
review,
we
discuss
areas
improvement
at
each
stage
proteome
profiling
data
analysis
that
includes
processing
MS-based
data,
development,
effect
overall
quality
profiles.
We
also
overview
optimization
experimental
strategies
prioritization
an
increased
number
independent
biological
replicates
over
evaluated
temperatures.
Molecules,
Journal Year:
2023,
Volume and Issue:
28(12), P. 4859 - 4859
Published: June 20, 2023
Although
the
use
of
detergents
in
thermal
proteome
profiling
(TPP)
has
become
a
common
practice
to
identify
membrane
protein
targets
complex
biological
samples,
surprisingly,
there
is
no
proteome-wide
investigation
into
impacts
detergent
introduction
on
target
identification
performance
TPP.
In
this
study,
we
assessed
TPP
presence
commonly
used
non-ionic
or
zwitterionic
using
pan-kinase
inhibitor
staurosporine,
our
results
showed
that
addition
either
these
significantly
impaired
at
optimal
temperature
for
soluble
identification.
Further
destabilized
and
increased
precipitation.
By
lowering
applied
point,
with
improved
comparable
absence
detergents.
Our
findings
provide
valuable
insight
how
select
appropriate
range
when
are
addition,
also
suggest
combination
heat
may
serve
as
novel
precipitation-inducing
force
can
be
Journal of Medicinal Chemistry,
Journal Year:
2022,
Volume and Issue:
65(18), P. 12014 - 12030
Published: Sept. 12, 2022
Inflammatory
responses
are
important
in
cancer,
particularly
the
context
of
monocyte-rich
aggressive
myeloid
neoplasm.
We
developed
a
label-free
cellular
phenotypic
drug
discovery
assay
to
identify
anti-inflammatory
drugs
human
monocytes
derived
from
acute
leukemia
(AML),
by
tracking
several
features
ionizing
only
2500
cells
using
matrix-assisted
laser
desorption/ionization-time
flight
(MALDI-TOF)
mass
spectrometry.
A
proof-of-concept
screen
showed
that
BCR-ABL
inhibitor
nilotinib,
but
not
structurally
similar
imatinib,
blocks
inflammatory
responses.
In
order
(off-)targets
we
performed
thermal
proteome
profiling
(TPP).
Unlike
nilotinib
and
other
later-generation
inhibitors
bind
p38α
inhibit
p38α-MK2/3
signaling
axis,
which
suppressed
pro-inflammatory
cytokine
expression,
cell
adhesion,
innate
immunity
markers
activated
AML.
Thus,
our
study
provides
tool
for
new
drugs,
could
contribute
treatment
inflammation
neoplasms
diseases.
