Drug delivery for platinum therapeutics
Journal of Controlled Release,
Год журнала:
2025,
Номер
380, С. 503 - 523
Опубликована: Фев. 11, 2025
Язык: Английский
Small Molecule Drugs Triggered the Activation of Macrocycle Masked Proteins
Nano Letters,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 13, 2025
On-demand
activation
of
prodrugs
represents
an
emerging
and
fast
developing
strategy
to
improve
the
therapeutic
index
certain
drugs.
However,
strategies
generate
protein-based
with
controllable
are
still
limited.
Here,
we
present
a
supramolecular
masking
that
enables
on-demand
macrocycle-masked
proteins
Food
Drug
Administration
(FDA)-approved
oral
Proteins
interest
were
engineered
incorporate
two
N-terminal
peptide
motifs,
which
dimerized
by
cucurbit[8]uril
(CB[8])
form
mask
sterically
blocks
functional
protein
interfaces,
inhibiting
interactions
targets
or
substrates.
The
inhibitory
effect
was
selectively
reversed
amantadine
memantine
restore
activity.
This
validated
across
various
classes,
including
antibodies,
cytokines,
enzymes.
Activation
CB[8]-masked
further
demonstrated
in
living
mice
via
FDA-approved
small
molecule
treatments.
Our
method
provided
for
selective
development
next-generation
therapeutics.
Язык: Английский
Fundamental properties and principal areas of focus in antibody-drug conjugates formulation development
Antibody Therapeutics,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 9, 2025
Abstract
Antibody–drug
conjugates
(ADCs)
have
emerged
as
a
rapidly
expanding
class
of
therapeutics
driven
by
their
superior
specificity
and
clinical
efficacy.
14
out
16
commercially
approved
ADCs
are
formulated
lyophilized
forms
because
ADC
is
generally
considered
to
be
less
stable
than
unmodified
antibody.
The
formulation
development
for
ADCs,
particularly
liquid
formulation,
presents
unique
challenges
due
intricate
structural
complexity,
physicochemical
properties,
degradation
pathways.
This
review
provides
the
first
comprehensive
analysis
strategies
employed
in
commercial
ADCs.
Furthermore,
this
discusses
key
areas
focus
throughout
workflow,
spanning
from
initial
final
stage
drug
product
manufacturing.
In
addition,
we
identify
analyze
distinctive
technical
compared
unconjugated
antibody,
while
proposing
potential
solutions
these
challenges.
Finally,
offer
strategic
perspectives
on
future
directions
advance
promising
therapeutic
modality.
Язык: Английский
Comparison of conventional and green approaches to the synthesis of aromatic Schiff bases
Polish Journal of Chemical Technology,
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 1, 2024
Abstract
The
chemical
industry
is
one
of
the
key
elements
in
improving
quality
human
life.
At
same
time,
it
generates
pollution
influencing
ecosystem
and
our
health.
To
limit
or
remove
some
reasons
for
two
decades
less
harmful
approaches
to
synthesis
various
organic
compounds
were
developed.
Among
compounds,
azomethines,
also
known
as
Schiff
bases,
are
particular
interest
biochemistry,
medicine,
pharmacy.
For
over
twenty
years
many
novel
these
have
been
investigated.
Toxic
solvents
(benzene,
toluene)
replaced
with
water,
fruit
juice,
white
egg,
cases,
temperature
time
process
significantly
reduced.
In
review,
conventional
green
bases
presented
a
focus
on
effectiveness
methods,
including
advantages
disadvantages.
Язык: Английский
Geldanamycins: Potent Hsp90 Inhibitors with Significant Potential in Cancer Therapy
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(20), С. 11293 - 11293
Опубликована: Окт. 20, 2024
Geldanamycin,
an
ansa-macrolide
composed
of
a
rigid
benzoquinone
ring
and
aliphatic
ansa-bridge,
was
isolated
from
Streptomyces
hygroscopicus.
Geldanamycin
is
potent
heat
shock
protein
inhibitor
with
remarkable
antiproliferative
activity.
However,
it
shows
pronounced
hepatotoxicity
in
animal
models
unfavorable
pharmacokinetic
properties.
Four
geldanamycin
analogs
have
progressed
through
various
phases
clinical
trials,
but
none
yet
completed
evaluation
or
received
FDA
approval.
To
enhance
the
efficacy
these
Hsp90
inhibitors,
strategies
such
as
prodrug
approaches
nanocarrier
delivery
systems
could
be
employed
to
minimize
systemic
organ
toxicity.
Furthermore,
exploring
new
drug
combinations
may
help
overcome
resistance,
potentially
improving
therapeutic
outcomes.
This
review
discusses
mechanism
action
geldanamycin,
its
properties,
alleviate
toxicity
maximize
efficacy.
The
main
focus
on
those
derivatives
that
trials
shown
important
vivo
activity
preclinical
models.
Язык: Английский
Molecular Matchmakers: Bioconjugation Techniques Enhance Prodrug Potency for Immunotherapy
Molecular Pharmaceutics,
Год журнала:
2024,
Номер
22(1), С. 58 - 80
Опубликована: Ноя. 21, 2024
Cancer
patients
suffer
greatly
from
the
severe
off-target
side
effects
of
small
molecule
drugs,
chemotherapy,
and
radiotherapy─therapies
that
offer
little
protection
following
remission.
Engineered
immunotherapies─including
cytokines,
immune
checkpoint
blockade,
monoclonal
antibodies,
CAR-T
cells─provide
better
targeting
future
tumor
growth
prevention.
Still,
issues
such
as
ineffective
activation,
immunogenicity,
remain
primary
concerns.
"Prodrug"
therapies─classified
therapies
administered
inactive
then
selectively
activated
to
control
time
area
release─hold
significant
promise
in
overcoming
these
Bioconjugation
techniques
(e.g.,
natural
linker
conjugation,
bioorthogonal
reactions,
noncanonical
amino
acid
incorporation)
enable
rapid
homogeneous
synthesis
prodrugs
selective
loading
immunotherapeutic
agents
carrier
molecules
protecting
groups
prevent
after
administration.
Several
prodrug
activation
mechanisms
have
been
highlighted
for
cancer
therapeutics,
including
endogenous
by
hypoxic
or
acidic
conditions
common
tumors,
exogenous
targeted
cleavage,
stimuli-responsive
light
dual-stimuli
which
adds
specificity
combining
mechanisms.
This
review
will
explore
modern
conjugation
options,
focusing
on
how
strategies
can
enhance
immunotherapy
responses
improve
patient
outcomes.
We
also
discuss
implications
computational
methodology
therapy
design
recommend
procedures
determine
where
conjugate
systems
"prodrug"
onto
therapeutic
safety
delivery
platforms.
Язык: Английский