In situ peptide assembly for cell membrane rewiring in tumor therapy
Journal of Controlled Release,
Год журнала:
2025,
Номер
unknown, С. 113637 - 113637
Опубликована: Март 1, 2025
Язык: Английский
A CXCR4-targeted immunomodulatory nanomedicine for photodynamic amplified immune checkpoint blockade therapy against breast cancer
Acta Biomaterialia,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 1, 2025
Язык: Английский
Discovery of Dual PD-L1/HDAC3 Inhibitors for Tumor Immunotherapy
Journal of Medicinal Chemistry,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 15, 2025
Targeting
programmed
cell
death
protein-1
(PD-1)/programmed
death-ligand
1
(PD-L1)
pathway
has
been
considered
as
one
of
the
most
promising
strategies
for
tumor
immunotherapy.
However,
single-target
PD-1/PD-L1
inhibitors
frequently
exhibit
limited
efficacy,
highlighting
urgent
need
new
therapies.
Herein,
a
series
dual
PD-L1/HDAC3
were
developed
through
pharmacophore
fusion
strategy
first
time.
Among
them,
compound
PH3
was
identified
inhibitor,
with
potent
inhibitory
activity
(IC50
=
89.4
nM)
and
selective
HDAC3
107
nM).
Moreover,
exhibited
superior
in
vitro
antitumor
activities
immune
activation
effects.
Additionally,
showed
dose-dependent
efficacy
B16-F10
melanoma
mouse
model
without
obvious
toxicity.
Furthermore,
increased
infiltration
CD3+CD8+
CD3+CD4+
cells
microenvironment.
Collectively,
represented
novel
inhibitor
deserving
further
investigation
immunotherapy
agent.
Язык: Английский
Targeted protein degradation with small molecules for cancer immunotherapy
Asian Journal of Pharmaceutical Sciences,
Год журнала:
2025,
Номер
unknown, С. 101058 - 101058
Опубликована: Апрель 1, 2025
Язык: Английский
Fatty acid synthase (FASN) is a tumor-cell-intrinsic metabolic checkpoint restricting T-cell immunity
Cell Death Discovery,
Год журнала:
2024,
Номер
10(1)
Опубликована: Сен. 30, 2024
Язык: Английский
Small Molecule Inhibitors Targeting PD-L1, CTLA4, VISTA, TIM-3, and LAG3 for Cancer Immunotherapy (2020-2024)
European Journal of Medicinal Chemistry,
Год журнала:
2024,
Номер
283, С. 117141 - 117141
Опубликована: Дек. 5, 2024
Язык: Английский
Intrinsic PD‐L1 Degradation Induced by a Novel Self‐Assembling Hexapeptide for Enhanced Cancer Immunotherapy
Advanced Science,
Год журнала:
2024,
Номер
12(2)
Опубликована: Ноя. 12, 2024
Abstract
Programmed
death‐ligand
1
(PD‐L1)
is
a
critical
immune
checkpoint
protein
that
facilitates
tumor
evasion.
While
antibody‐based
PD‐1/PD‐L1
inhibitors
have
shown
promise,
their
limitations
necessitate
the
development
of
alternative
therapeutic
strategies.
This
work
addresses
these
challenges
by
developing
hexapeptide,
KFM
(Lys‐Phe‐Met‐Phe‐Met‐Lys),
capable
both
directly
downregulating
PD‐L1
and
self‐assembling
into
ROS‐responsive
supramolecular
hydrogel.
dual
functionality
allows
Gel
to
function
as
localized
drug
delivery
system
inhibitor.
Loading
hydrogel
with
mitoxantrone
(MTX)
metformin
(MET)
further
enhances
effect
combining
chemotherapy
downregulation.
In
vitro
in
vivo
studies
demonstrate
significant
growth
inhibition,
increased
CD8+
T
cell
infiltration,
reduced
intratumoral
expression
following
peritumoral
administration.
Mechanistically,
promotes
degradation
via
ubiquitin‐dependent
pathway.
“carrier‐free”
expands
role
hydrogels
beyond
passive
carriers
active
immunotherapeutic
agents,
offering
promising
new
strategy
for
cancer
therapy.
Язык: Английский
Discovery of Small Molecules for Autophagy-lysosome Degradation of Immune Checkpoint Proteins
European Journal of Medicinal Chemistry,
Год журнала:
2024,
Номер
280, С. 116958 - 116958
Опубликована: Окт. 16, 2024
Язык: Английский
Advancing Cancer Immunotherapy through Engineering New PD-L1 Degraders: A Comprehensive Study from Small Molecules to PD-L1-Specific Peptide–Drug Conjugates
Journal of Medicinal Chemistry,
Год журнала:
2024,
Номер
67(21), С. 19216 - 19233
Опубликована: Окт. 18, 2024
Despite
the
considerable
achievements
of
antibodies
targeting
PD-1/PD-L1
in
cancer
immunotherapy,
limitations
antitumor
immune
response
and
pharmacokinetics
hinder
their
clinical
adoption.
Small
molecules
toward
PD-L1
degradation
signifies
an
innovative
avenue
to
modulate
axis.
Herein,
we
unveil
a
comprehensive
engineering
involving
development
new
degraders
based
on
berberine
(BBR)
palmatine
(PMT)
bioactive
frameworks
explore
translational
potential
for
immunotherapy
using
peptide-drug
conjugate
strategy.
Chemical
modifications
at
O-9
position
PMT
dramatically
enhance
capacity.
Further
conjugation
with
anti-PD-L1
peptide
featuring
disulfide
linkers
enables
efficient
GSH-specific
prodrug
activation,
yielding
synergistic
immunotherapeutic
benefits
through
both
external
blockade
internal
mechanisms.
This
work
elucidates
compelling
charm
discovery
application
degraders,
offering
solutions
challenges
advancing
widespread
clinics.
Язык: Английский