Effect of Drug-to-Protein Reaction Kinetics on the Results of Thermal Proteome Profiling
Analytical Chemistry,
Journal Year:
2024,
Volume and Issue:
97(1), P. 22 - 26
Published: Dec. 25, 2024
In
this
Letter,
a
two-term
formalism
for
constructing
protein
solubility
curves
in
thermal
proteome
profiling
(TPP)
is
considered,
which
takes
into
account
the
efficiency
of
drug-protein
binding
reaction.
When
reaction
incomplete,
results
distortion
otherwise
sigmoidal
shape
curve
after
drug
treatment,
often
observed
experiments.
This
may
be
significant
enough
to
disqualify
corresponding
from
list
target
candidates,
thus
negatively
affecting
TPP
data
analysis.
To
further
assist
analysis,
we
also
developed
simulation
software
visualize
discussed
effect.
Several
experimental
sets
recent
studies
have
been
reprocessed,
and
demonstrate
few
examples
that
proposed
equation
fits
correctly
with
distorted
shapes,
highlighting
previously
unrecognized
targets.
Language: Английский
Phenotypic approaches for CNS drugs
Trends in Pharmacological Sciences,
Journal Year:
2024,
Volume and Issue:
45(11), P. 997 - 1017
Published: Oct. 21, 2024
Central
nervous
system
(CNS)
drug
development
is
plagued
by
high
clinical
failure
rate.
Phenotypic
assays
promote
translation
of
drugs
reducing
complex
brain
diseases
to
measurable,
clinically
valid
phenotypes.
We
critique
recent
platforms
integrating
patient-derived
cells,
which
most
accurately
recapitulate
CNS
disease
phenotypes,
with
higher
throughput
models,
including
immortalized
balance
validity
and
scalability.
These
were
screened
conventional
commercial
chemogenomic
compound
libraries.
explore
emerging
library
curation
strategies
improve
hit
rate
quality,
screening
novel
fragment
libraries
as
alternatives,
for
more
tractable
target
deconvolution.
The
relevant
models
used
in
these
could
harbor
important,
unidentified
targets,
so
we
review
evolving
agnostic
deconvolution
approaches,
chemical
proteomics
artificial
intelligence
(AI),
aid
phenotypic
mechanism
elucidation,
thereby
facilitating
rational
hit-to-drug
optimization.
Language: Английский
Past, current, and future of molecular pathway analysis
Elsevier eBooks,
Journal Year:
2024,
Volume and Issue:
unknown, P. 3 - 41
Published: Dec. 6, 2024
Language: Английский
Molecular data for the pathway analysis
Elsevier eBooks,
Journal Year:
2024,
Volume and Issue:
unknown, P. 43 - 62
Published: Dec. 6, 2024
Language: Английский
Investigating Antiprotozoal Chemotherapies with Novel Proteomic Tools—Chances and Limitations: A Critical Review
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(13), P. 6903 - 6903
Published: June 24, 2024
Identification
of
drug
targets
and
biochemical
investigations
on
mechanisms
action
are
major
issues
in
modern
development.
The
present
article
is
a
critical
review
the
classical
"one
drug"-"one
target"
paradigm.
In
fact,
novel
methods
for
target
deconvolution
investigation
resistant
strains
based
protein
mass
spectrometry
have
shown
that
multiple
gene
products
adaptation
involved
responses
pathogens
to
xenobiotics
rather
than
one
single
or
product.
Resistance
drugs
may
be
linked
differential
expression
other
proteins
those
interacting
with
binding
studies
result
complex
cell
physiological
adaptation.
Consequently,
unraveling
needs
approaches
beyond
proteomics.
This
focused
protozoan
pathogens.
conclusions
can,
however,
extended
chemotherapies
against
cancer.
Language: Английский