Most
cancers
exhibit
aneuploidy,
but
its
functional
significance
in
tumor
development
is
controversial.
Here,
we
describe
ReDACT
(Restoring
Disomy
Aneuploid
cells
using
CRISPR
Targeting),
a
set
of
chromosome
engineering
tools
that
allow
us
to
eliminate
specific
aneuploidies
from
cancer
genomes.
Using
ReDACT,
created
panel
isogenic
have
or
lack
common
aneuploidies,
and
demonstrate
trisomy
1q
required
for
malignant
growth
harboring
this
alteration.
Mechanistically,
gaining
increases
the
expression
Protein Science,
Год журнала:
2020,
Номер
30(1), С. 187 - 200
Опубликована: Окт. 18, 2020
The
BioGRID
(Biological
General
Repository
for
Interaction
Datasets,
thebiogrid.org)
is
an
open-access
database
resource
that
houses
manually
curated
protein
and
genetic
interactions
from
multiple
species
including
yeast,
worm,
fly,
mouse,
human.
~1.93
million
in
can
be
used
to
build
complex
networks
facilitate
biomedical
discoveries,
particularly
as
related
human
health
disease.
All
content
primary
experimental
evidence
the
literature,
includes
both
focused
low-throughput
studies
large
high-throughput
datasets.
also
captures
post-translational
modifications
or
gene
with
bioactive
small
molecules
many
known
drugs.
A
built-in
network
visualization
tool
combines
all
annotations
allows
users
generate
graphs
of
protein,
chemical
interactions.
In
addition
general
curation
across
species,
undertakes
themed
projects
specific
aspects
cellular
regulation,
example
ubiquitin-proteasome
system,
well
disease
areas,
such
SARS-CoV-2
virus
causes
COVID-19
severe
acute
respiratory
syndrome.
recent
extension
BioGRID,
named
Open
CRISPR
Screens
(ORCS,
orcs.thebiogrid.org),
single
mutant
phenotypes
published
high
throughput
genome-wide
CRISPR/Cas9-based
screens.
BioGRID-ORCS
contains
datasets
over
1,042
screens
carried
out
date
human,
mouse
fly
cell
lines.
research
community
freely
access
data
through
web
interface,
standardized
file
downloads,
via
model
organism
databases
partner
meta-databases.
Acta Pharmaceutica Sinica B,
Год журнала:
2022,
Номер
12(7), С. 3049 - 3062
Опубликована: Фев. 11, 2022
Ninety
percent
of
clinical
drug
development
fails
despite
implementation
many
successful
strategies,
which
raised
the
question
whether
certain
aspects
in
target
validation
and
optimization
are
overlooked?
Current
overly
emphasizes
potency/specificity
using
structure‒activity-relationship
(SAR)
but
overlooks
tissue
exposure/selectivity
disease/normal
tissues
structure‒tissue
exposure/selectivity–relationship
(STR),
may
mislead
candidate
selection
impact
balance
dose/efficacy/toxicity.
We
propose
exposure/selectivity–activity
relationship
(STAR)
to
improve
optimization,
classifies
candidates
based
on
drug's
potency/selectivity,
exposure/selectivity,
required
dose
for
balancing
efficacy/toxicity.
Class
I
drugs
have
high
specificity/potency
needs
low
achieve
superior
efficacy/safety
with
success
rate.
II
requires
efficacy
toxicity
be
cautiously
evaluated.
III
relatively
(adequate)
manageable
often
overlooked.
IV
achieves
inadequate
efficacy/safety,
should
terminated
early.
STAR
studies
development.
Translational Medicine Communications,
Год журнала:
2019,
Номер
4(1)
Опубликована: Ноя. 18, 2019
Abstract
A
rift
that
has
opened
up
between
basic
research
(bench)
and
clinical
patients
(bed)
who
need
their
new
treatments,
diagnostics
prevention,
this
is
widening
getting
deeper.
The
crisis
involving
the
“translation”
of
scientific
findings
in
a
laboratory
setting
into
human
applications
potential
treatments
or
biomarkers
for
disease
widely
recognized
both
academia
industry.
Despite
attempts
have
been
made
academic
industry
settings
to
mitigate
problem,
high
attrition
rates
drug
development
problem
with
reproducibility
translatability
preclinical
remain
fact
return
on
investment
limited
terms
impact.
Here
I
provide
an
overview
challenges
facing
development,
translational
discordance
specific
focus
number
“culprits”
including
poor
hypothesis,
irreproducible
data,
ambiguous
models,
statistical
errors,
influence
organizational
structures,
lack
incentives
setting,
governmental
funding
mechanisms,
relevance
research,
insufficient
transparency,
data
sharing
research.
further
some
suggestions
strategies
include
aspects
open
innovation
entrepreneurship,
decision
making
overcome
each
many
problems
during
discovery
process
more
dynamically
adjust
broader
feedback.
Nucleic Acids Research,
Год журнала:
2021,
Номер
50(D1), С. D1398 - D1407
Опубликована: Окт. 5, 2021
Drug
discovery
relies
on
the
knowledge
of
not
only
drugs
and
targets,
but
also
comparative
agents
targets.
These
include
poor
binders
non-binders
for
developing
tools,
prodrugs
improved
therapeutics,
co-targets
therapeutic
targets
multi-target
strategies
off-target
investigations,
collective
structure-activity
drug-likeness
landscapes
enhanced
drug
feature.
However,
such
valuable
data
are
inadequately
covered
by
available
databases.
In
this
study,
a
major
update
Therapeutic
Target
Database,
previously
featured
in
NAR,
was
therefore
introduced.
This
includes
(a)
34
861
12
683
1308
targets;
(b)
534
prodrug-drug
pairs
121
(c)
1127
672
regulated
642
approved
624
clinical
trial
drugs;
(d)
427
262
active
1565
(e)
profiles
drug-like
properties
33
598
1102
Moreover,
variety
additional
function
provided,
which
cross-links
to
target
structure
PDB
AlphaFold,
159
1658
newly
emerged
drugs,
advanced
search
multi-entry
sequences
or
structures.
The
database
is
accessible
without
login
requirement
at:
https://idrblab.org/ttd/.
