Investigation of monoclonal antibody CSX-1004 for fentanyl overdose
Nature Communications,
Год журнала:
2023,
Номер
14(1)
Опубликована: Дек. 5, 2023
Abstract
The
opioid
crisis
in
the
United
States
is
primarily
driven
by
highly
potent
synthetic
fentanyl
leading
to
>70,000
overdose
deaths
annually;
thus,
new
therapies
for
are
urgently
needed.
Here,
we
present
first
clinic-ready,
fully
human
monoclonal
antibody
CSX-1004
with
picomolar
affinity
and
related
analogs.
In
mice
reverses
antinociception
intractable
respiratory
depression
caused
ultrapotent
carfentanil.
Moreover,
toxicokinetic
evaluation
a
repeat-dose
rat
study
tissue
cross-reactivity
reveals
favorable
pharmacokinetic
profile
of
no
safety-related
issues.
Using
translational
non-human
primate
(NHP)
model
depression,
demonstrate
CSX-1004-mediated
protection
from
repeated
challenges
3-4
weeks.
Furthermore,
treatment
produces
up
15-fold
potency
reduction
NHP
respiration,
operant
responding
assays
without
affecting
non-fentanyl
opioids
like
oxycodone.
Taken
together,
our
data
establish
feasibility
as
promising
candidate
medication
preventing
reversing
fentanyl-induced
overdose.
Язык: Английский
Nanotherapeutics for Alleviating Anesthesia‐Associated Complications
Advanced Science,
Год журнала:
2024,
Номер
11(15)
Опубликована: Фев. 11, 2024
Abstract
Current
management
of
anesthesia‐associated
complications
falls
short
in
terms
both
efficacy
and
safety.
Nanomaterials
with
versatile
properties
unique
nano‐bio
interactions
hold
substantial
promise
as
therapeutics
for
addressing
these
complications.
This
review
conducts
a
thorough
examination
the
existing
nanotherapeutics
highlights
strategies
developing
prospective
nanomedicines
to
mitigate
anesthetics‐related
toxicity.
Initially,
general,
regional,
local
anesthesia
along
commonly
used
anesthetics
related
prevalent
side
effects
are
introduced.
Furthermore,
employing
nanotechnology
prevent
alleviate
is
systematically
demonstrated
from
three
aspects,
that
is,
1)
safe
nano‐formulization
anesthetics;
2)
nano‐antidotes
sequester
overdosed
alter
their
pharmacokinetics;
3)
pharmacodynamic
activities
treat
Finally,
prospects
challenges
facing
clinical
translation
anesthesia‐related
discussed.
work
provides
comprehensive
roadmap
effective
toxicity,
which
can
potentially
revolutionize
Язык: Английский
Development of fentanyl-specific monoclonal antibody (mAb) to antagonize the pharmacological effects of fentanyl
Toxicology and Applied Pharmacology,
Год журнала:
2024,
Номер
486, С. 116918 - 116918
Опубликована: Апрель 1, 2024
Язык: Английский
The fentanyl-specific antibody FenAb024 can shield against carfentanil effects
Toxicology Letters,
Год журнала:
2024,
Номер
396, С. 1 - 10
Опубликована: Апрель 6, 2024
The
surge
in
opioid-related
deaths,
driven
predominantly
by
fentanyl
and
its
synthetic
derivatives,
has
become
a
critical
public
health
concern,
which
is
particularly
evident
the
United
States.
While
situation
less
severe
Europe,
European
Monitoring
Centre
for
Drugs
Drug
Addiction
reports
rise
drug
overdose
with
emerging
concerns
about
impact
of
fentanyl-related
molecules.
Synthetic
opioids,
initially
designed
medical
use,
have
infiltrated
illicit
markets
due
to
their
low
production
costs
high
potency,
carfentanil
posing
additional
threats,
including
potential
chemical
weaponization.
Existing
mitigation
heavily
relies
on
naloxone,
requiring
timely
intervention
caregiver
presence,
while
therapeutic
prevention
strategies
face
many
access
challenges.
To
provide
an
treatment
option,
we
propose
use
fentanyl-specific
monoclonal
antibody
(mAb),
as
non-opioid
method
prophylaxis
against
carfentanil.
This
mAb
shows
protection
from
opioid
effects
pre-clinical
murine
model.
mAbs
could
emerge
versatile
countermeasure
civilian
biodefense
settings,
offering
novel
approach
combat
opioid-associated
mortality.
Язык: Английский
Fentanyl–Antibody Interaction as a Novel Strategy against Opiates and Opioids Abuse
Journal of Medicinal Chemistry,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 3, 2025
While
naloxone
remains
the
antidote
for
opioid
overdoses,
more
efficient
tools
are
required
to
effectively
combat
this
growing
crisis.
Vaccines
and
antibodies
targeting
substances
of
abuse
appear
be
a
novel
promising
approach
tackling
fentanyl
epidemic.
After
an
initial
in-depth
rundown
on
pharmacodynamics
involved
from
structural
mechanistic
standpoint,
brief
overview
pharmacological
approaches
used
in
clinical
settings
managing
overdoses
addiction,
Perspective
will
mainly
focused
these
innovative
strategies,
based
development
binding
sequestering
their
generation
vivo
through
vaccines.
The
most
examined,
production
techniques
potential
applications,
analyzing
structures
mechanisms
antibody-substance
interactions
comparing
with
receptor
processes.
Язык: Английский
In vitro biophysical and pharmacological profiling predicts in vivo efficacy of anti-carfentanil monoclonal antibodies in mice
Biochemical and Biophysical Research Communications,
Год журнала:
2025,
Номер
770, С. 151995 - 151995
Опубликована: Май 10, 2025
Язык: Английский
Identification and biophysical characterization of a novel domain-swapped camelid antibody specific for fentanyl
Journal of Biological Chemistry,
Год журнала:
2024,
Номер
300(8), С. 107502 - 107502
Опубликована: Июнь 28, 2024
Язык: Английский
Structure-Based Engineering of Monoclonal Antibodies for Improved Binding to Counteract the Effects of Fentanyl and Carfentanil
ACS Omega,
Год журнала:
2024,
Номер
9(41), С. 42506 - 42519
Опубликована: Окт. 7, 2024
The
opioid
overdose
epidemic
is
a
growing
and
evolving
public
health
crisis
fueled
by
the
widespread
presence
of
fentanyl
analogues
(F/FAs)
in
both
street
mixtures
counterfeit
pills.
To
expand
current
treatment
options,
drug-targeting
monoclonal
antibodies
(mAbs)
offer
viable
therapeutic
for
pre-
postexposure
clinical
scenarios.
This
study
reports
isolation,
vitro
characterization,
vivo
efficacy
two
murine
mAb
families
targeting
fentanyl,
carfentanil,
or
both.
Because
humanization
mAbs
CDR
grafting
negatively
impacted
affinity
crystal
structures
complex
with
carfentanil
were
analyzed
to
identify
key
residues
involved
ligand
binding
versus
humanized
structures,
site-directed
mutagenesis
was
used
verify
their
functional
importance.
structural
analysis
identified
framework
residue,
Tyr36,
present
germline
sequence
mAbs,
which
critical
carfentanil.
These
studies
emphasize
importance
considerations
engineering
optimize
small
molecules
including
opioids
other
drugs
interest.
Язык: Английский
Engineering antibodies with cancer‐associated binding sites
BMEMat,
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 27, 2024
Abstract
Cancer
immunotherapy
has
appeared
as
a
prospective
therapeutic
modality.
Therapeutic
antibodies
induced
in
an
vitro
expression
system
act
“targeting
missiles”
against
tumor‐associated
binding
sites,
and
subsequently,
immune
attack
on
tumors
is
restored
or
boosted.
These
antibody
regimens
are
engineered
towards
enhanced
Fc
efficacy,
humanization,
fragmentation
to
specifically
recognize
bind
effective
targets.
The
challenge
lies
obtaining
efficient
with
low
response
rates,
acquisition
of
resistance,
immune‐related
undesirable
effects
artificially
designed
antibodies,
which
crucial
for
enhancing
clinical
efficacy.
This
review
provides
in‐depth
introduction
that
perform
direct/indirect
roles
cancer
treatment
by
checkpoints,
co‐stimulatory
receptors,
extracellular
membrane
receptors.
It
also
discusses
how
kill
modulate
microenvironment
tumor
through
these
classification
systems
production
summarized
guide
appropriate
selection
based
different
specificities.
Understanding
sources,
ongoing
evaluation
antigen
research
pave
the
way
designing
antibody‐based
regimens.
Язык: Английский