Medicinal Research Reviews,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 9, 2025
ABSTRACT
Proteins
hold
pivotal
importance
since
many
diseases
manifest
changes
in
protein
activity.
Proteomics
techniques
provide
a
comprehensive
exploration
of
structure,
abundance,
and
function
biological
samples,
enabling
the
holistic
characterization
overall
organisms.
Nowadays,
breadth
emerging
methodologies
proteomics
is
unprecedentedly
vast,
with
constant
optimization
technologies
sample
processing,
data
collection,
analysis,
its
scope
application
steadily
transitioning
from
bench
to
clinic.
Here,
we
offer
an
insightful
review
technical
developments
applications
biomedicine
over
past
5
years.
We
focus
on
profound
contributions
profiling
disease
spectra,
discovering
new
biomarkers,
identifying
promising
drug
targets,
deciphering
alterations
conformation,
unearthing
protein–protein
interactions.
Moreover,
summarize
cutting‐edge
potential
breakthroughs
pipeline
principal
challenges
proteomics.
Based
these,
aspire
broaden
applicability
inspire
researchers
enhance
our
understanding
complex
systems
by
utilizing
such
techniques.
Bioorganic & Medicinal Chemistry,
Год журнала:
2024,
Номер
105, С. 117718 - 117718
Опубликована: Апрель 12, 2024
Targeted
protein
degradation
(TPD)
has
recently
emerged
as
an
exciting
new
drug
modality.
However,
the
strategy
of
developing
small
molecule-based
degraders
evolved
over
past
two
decades
and
now
established
molecular
tags
that
are
already
in
clinical
use,
well
chimeric
molecules,
PROteolysis
TArgeting
Chimeras
(PROTACs),
based
mainly
on
ligand
systems
developed
for
E3
ligases
CRBN
VHL.
The
large
size
human
ligase
family
suggests
PROTACs
can
be
by
targeting
a
diversity
ligases,
some
which
have
restricted
expression
patterns
with
potential
to
design
disease-
or
tissue-specific
degraders.
Indeed,
many
ligands
been
published
recently,
confirming
druggability
ligases.
This
review
summarises
recent
data
highlights
challenges
these
molecules
into
efficient
rivalling
degrader
systems.
Journal of Chemical Information and Modeling,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 8, 2025
Targeted
covalent
inhibition
is
a
powerful
therapeutic
modality
in
the
drug
discoverer's
toolbox.
Recent
advances
discovery,
particular,
targeting
cysteines,
have
led
to
significant
breakthroughs
for
traditionally
challenging
targets
such
as
mutant
KRAS,
which
implicated
diverse
human
cancers.
However,
identifying
cysteines
targeted
difficult
task,
experimental
and
silico
tools
shown
limited
accuracy.
Using
recently
released
CovPDB
CovBinderInPDB
databases,
we
trained
tested
interpretable
machine
learning
(ML)
models
identify
that
are
liable
be
covalently
modified
(i.e.,
"ligandable"
cysteines).
We
explored
myriad
physicochemical
features
(pKa,
solvent
exposure,
residue
electrostatics,
etc.)
protein–ligand
pocket
descriptors
our
ML
models.
Our
final
logistic
regression
model
achieved
median
F1
score
of
0.73
on
held-out
test
sets.
When
small
sample
holo
proteins,
also
showed
reasonable
performance,
accurately
predicting
most
ligandable
cysteine
cases.
Taken
together,
these
results
indicate
can
predict
potential
privileging
more
likely
selective
rather
than
purely
reactive.
release
this
tool
scientific
community
CovCysPredictor.
Medicinal Research Reviews,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 9, 2025
ABSTRACT
Proteins
hold
pivotal
importance
since
many
diseases
manifest
changes
in
protein
activity.
Proteomics
techniques
provide
a
comprehensive
exploration
of
structure,
abundance,
and
function
biological
samples,
enabling
the
holistic
characterization
overall
organisms.
Nowadays,
breadth
emerging
methodologies
proteomics
is
unprecedentedly
vast,
with
constant
optimization
technologies
sample
processing,
data
collection,
analysis,
its
scope
application
steadily
transitioning
from
bench
to
clinic.
Here,
we
offer
an
insightful
review
technical
developments
applications
biomedicine
over
past
5
years.
We
focus
on
profound
contributions
profiling
disease
spectra,
discovering
new
biomarkers,
identifying
promising
drug
targets,
deciphering
alterations
conformation,
unearthing
protein–protein
interactions.
Moreover,
summarize
cutting‐edge
potential
breakthroughs
pipeline
principal
challenges
proteomics.
Based
these,
aspire
broaden
applicability
inspire
researchers
enhance
our
understanding
complex
systems
by
utilizing
such
techniques.
