RSC Advances,
Journal Year:
2024,
Volume and Issue:
14(40), P. 29184 - 29188
Published: Jan. 1, 2024
An
efficient
Suzuki–Miyuara
reaction
was
developed
on
unprotected
ortho
-bromoanilines
providing
good
to
excellent
yields
a
wide
variety
of
substrates.
The
robustness
the
showcased
gram
scale.
RSC Medicinal Chemistry,
Journal Year:
2024,
Volume and Issue:
15(3), P. 809 - 831
Published: Jan. 1, 2024
Antibody-drug
conjugates
(ADCs)
comprise
3
components
of
wildly
differing
sizes:
antibody
(150
000
Da),
linker
(typically
<500
Da)
and
payload
Da).
While
the
drug-linker
makes
up
only
a
small
percent
ADC
it
has
disproportionately
massive
impact
on
all
aspects
ADC.
Replacing
maleimide
with
bromoacetamide
(BrAc)
affords
stable
attachment
to
cysteine,
supports
total
flexibility
for
design
more
homogenous
Optimisation
protease
cleavable
dipeptide
reduces
aggregation,
facilitates
moderation
physicochemical
properties
enables
long-term
stability
facilitate
subcutaneous
self-administration.
Payloads
are
designed
specifically
afford
optimal
Structural
information
SAR
guide
improve
both
potency
selectivity
molecule
target
improving
therapeutic
index
resulting
ADCs.
Minimising
solvent
exposed
hydrophobic
surface
area
improves
drug-like
ADC,
realisation
that
heteroatom
can
be
than
just
site
as
also
drive
adoption
prodrug
strategy
at
project
initiation
key
areas
medicinal
chemistry
drives.
For
an
symbiotic
relationship
three
structurally
disparate
requires
they
function
in
unison
huge
role
ensure
this
happens.
Antibody Therapeutics,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 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.
ACS Medicinal Chemistry Letters,
Journal Year:
2023,
Volume and Issue:
14(12), P. 1767 - 1773
Published: Nov. 21, 2023
Bispecific
antibodies
(BisAbs)
are
biotherapeutics
that
amalgamate
the
specificities
of
two
distinct
into
one
molecule,
however,
their
engineering
requires
genetic
modification
and
remains
time-consuming.
Therefore,
we
used
AJICAP
second-generation
technology,
which
drives
production
site-specific
conjugation
without
requirements,
to
generate
BisAbs.
Using
haloketone
chemistry
as
an
alternative
maleimide
chemistry,
successfully
produced
antibody
conjugates.
Pharmacokinetic
studies
revealed
haloketone-based
conjugate
was
stable
in
rat
plasma.
The
resultant
BisAbs
were
rigorously
evaluated,
surface
plasmon
resonance
measurements
flow
cytometry
analyses
confirmed
antigen
binding
remained
intact.
Additionally,
affinity
for
neonatal
Fc
receptor
(FcRn)
retained
after
conjugation.
Further
cytotoxicity
evaluation
emphasized
pronounced
activity
generated
This
novel
approach
introduces
a
fully
chemical,
strategy
capable
producing
BisAbs,
heralding
new
era
field
biotherapeutics.
Journal of Medicinal Chemistry,
Journal Year:
2024,
Volume and Issue:
67(11), P. 9495 - 9515
Published: May 23, 2024
We
describe
the
discovery
of
a
thioester-containing
glucocorticoid
receptor
modulator
(GRM)
payload
and
corresponding
antibody-drug
conjugate
(ADC).
Payload
Journal of Medicinal Chemistry,
Journal Year:
2024,
Volume and Issue:
67(18), P. 16222 - 16234
Published: Sept. 5, 2024
Toll-like
receptor
(TLR)
activation
converts
immunologically
inactive
tumors
into
active
by
activating
tumor
residing
antigen-presenting
cells
and
recruitment
of
cytotoxic
T
lymphocytes.
Targeted
immune
agonists
(TIAs)
are
antibody
drug
conjugates
with
small-molecule
TLR
agonist
payloads.
The
mechanism
action
TIAs
involves
antigen
recognition,
Fcγ-receptor-dependent
phagocytosis,
TLR-mediated
to
drive
killing
myeloid
cells.
Several
new
low
DAR
anti-HER2
conjugated
novel
TLR7
or
dual-TLR7/8
cleavable
noncleavable
linkers
were
synthesized
profiled.
In
vitro
studies
demonstrated
that
these
activate
only
in
the
presence
antigen-expressing
cancer
Evaluation
ELISpot-based
assays
confirmed
immunogenicity
constructs.
Systemic
administration
tumor-bearing
mice
resulted
reduction
at
doses.
These
results
provide
a
strong
rationale
for
further
development
as
class
immunotherapeutics.
RSC Medicinal Chemistry,
Journal Year:
2023,
Volume and Issue:
15(1), P. 355 - 365
Published: Nov. 27, 2023
A
glucocorticoid
receptor
modulator
(GRM)
was
conjugated
to
a
mouse
anti-TNF
antibody
using
various
dipeptide
linkers.
Impact
of
linkers
on
ADC
physical
properties,
including
solubility,
hydrophobicity,
and
aggregation
were
evaluated.
RSC Medicinal Chemistry,
Journal Year:
2023,
Volume and Issue:
15(2), P. 612 - 622
Published: Nov. 27, 2023
Maleimide
is
used
in
antibody–drug
conjugate
(ADC)
generation
to
attach
the
drug-linker
antibody.
linkers
with
hydrolysis-enabled
maleimides
were
designed.
Corresponding
ADCs
made
and
subjected
thermal
stress,
succinimide
ring
hydrolysis
drug
release
measured.