Angewandte Chemie,
Journal Year:
2023,
Volume and Issue:
135(51)
Published: Oct. 12, 2023
Abstract
To
interrogate
neural
circuits
and
crack
their
codes,
in
vivo
brain
activity
imaging
must
be
combined
with
spatiotemporally
precise
stimulation
three
dimensions
using
genetic
or
pharmacological
specificity.
This
challenge
requires
deep
penetration
focusing
as
provided
by
infrared
light
multiphoton
excitation,
has
promoted
two‐photon
photopharmacology
optogenetics.
However,
three‐photon
remains
to
demonstrated.
We
report
the
regulation
of
neuronal
zebrafish
larvae
excitation
a
photoswitchable
muscarinic
agonist
at
50
pM,
billion‐fold
lower
concentration
than
used
for
uncaging,
mid‐infrared
1560
nm,
longest
reported
photoswitch
wavelength.
Robust,
physiologically
relevant
photoresponses
allow
modulating
wild‐type
animals
spatiotemporal
precision.
Computational
calculations
predict
that
azobenzene‐based
ligands
have
high
absorption
cross‐section
can
directly
pulsed
light.
The
expansion
pharmacology
will
deeply
impact
basic
neurobiology
neuromodulation
phototherapies.
Chemical Science,
Journal Year:
2024,
Volume and Issue:
15(14), P. 5360 - 5367
Published: Jan. 1, 2024
Arylazobenzimidazoles
are
photoswitchable
privileged
structures
in
medicinal
chemistry.
Experimental
and
theoretical
studies
identified
compounds
with
visible
light
near-quantitative
bidirectional
photoswitching
highly
tunable
Z
-isomer
stability.
Chemistry - A European Journal,
Journal Year:
2024,
Volume and Issue:
30(22)
Published: Jan. 15, 2024
Proteases
are
involved
in
many
essential
biological
processes.
Dysregulation
of
their
activity
underlies
a
wide
variety
human
diseases.
Photopharmacology,
as
applied
on
various
classes
proteins,
has
the
potential
to
assist
protease
research
by
enabling
spatiotemporal
control
activity.
Moreover,
it
may
be
used
decrease
side-effects
protease-targeting
drugs.
In
this
review,
we
discuss
current
status
chemical
design
photoactivatable
proteases
inhibitors
and
application.
Additionally,
give
insight
into
future
possibilities
for
further
development
field
research.
Chemistry - A European Journal,
Journal Year:
2024,
Volume and Issue:
30(11)
Published: Jan. 11, 2024
Abstract
β
2
‐adrenergic
receptor
(β
‐AR)
agonists
are
used
for
the
treatment
of
asthma
and
chronic
obstructive
pulmonary
disease,
but
also
play
a
role
in
other
complex
disorders
including
cancer,
diabetes
heart
diseases.
As
cellular
molecular
mechanisms
various
cells
tissues
‐AR
remain
vastly
elusive,
we
developed
tools
this
investigation
with
high
temporal
spatial
resolution.
Several
photoswitchable
nanomolar
activity
were
synthesized.
The
most
potent
agonist
reasonable
switching
is
one‐digit
active,
trans
‐on
arylazopyrazole‐based
adrenaline
derivative
comprises
valuable
photopharmacological
properties
further
biological
studies
structural
accordance
to
native
ligand
adrenaline.
Angewandte Chemie International Edition,
Journal Year:
2023,
Volume and Issue:
62(51)
Published: Oct. 12, 2023
Abstract
To
interrogate
neural
circuits
and
crack
their
codes,
in
vivo
brain
activity
imaging
must
be
combined
with
spatiotemporally
precise
stimulation
three
dimensions
using
genetic
or
pharmacological
specificity.
This
challenge
requires
deep
penetration
focusing
as
provided
by
infrared
light
multiphoton
excitation,
has
promoted
two‐photon
photopharmacology
optogenetics.
However,
three‐photon
remains
to
demonstrated.
We
report
the
regulation
of
neuronal
zebrafish
larvae
excitation
a
photoswitchable
muscarinic
agonist
at
50
pM,
billion‐fold
lower
concentration
than
used
for
uncaging,
mid‐infrared
1560
nm,
longest
reported
photoswitch
wavelength.
Robust,
physiologically
relevant
photoresponses
allow
modulating
wild‐type
animals
spatiotemporal
precision.
Computational
calculations
predict
that
azobenzene‐based
ligands
have
high
absorption
cross‐section
can
directly
pulsed
light.
The
expansion
pharmacology
will
deeply
impact
basic
neurobiology
neuromodulation
phototherapies.
ACS Omega,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 18, 2025
Photopharmacology
offers
the
promise
of
optical
modulation
cellular
signaling
in
a
spatially
and
temporally
controlled
fashion
with
light-sensitive
molecules.
This
study
presents
first
small-molecule
photoswitchable
agonist
for
an
atypical
G
protein-coupled
receptor
(GPCR),
chemokine
3
(ACKR3).
Inspired
by
known
benzylpiperidine-based
ACKR3
scaffold,
12
azobenzene-containing
analogs
were
synthesized
characterized
their
interaction
ACKR3.
After
analysis
concise
Structure-Photochemistry
Structure-Affinity
Relationships
(SAR),
compound
3e
was
selected
as
best
series.
Compound
can
be
effectively
switched
from
its
thermodynamically
stable
trans
state
to
less
active
cis-isomer
photostationary
96%.
The
cis-
only
slowly
switches
back
(t
1/2,37°C
∼
15
days),
trans-3e
binds
activates
at
10-fold
lower
concentrations
compared
cis-isomer.
demonstrates
selectivity
within
wide
panel
receptors.
Using
recently
published
cryo-EM
structures
computational
studies,
binding
mode
is
proposed
that
perfectly
line
observed
SAR
reduction
upon
photoswitching.
(VUF25471)
ligand
GPCR
will
useful
tool
investigate
role
biological
settings.
Chemical Reviews,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 25, 2025
Cell-surface
receptors
are
vital
for
controlling
numerous
cellular
processes
with
their
dysregulation
being
linked
to
disease
states.
Therefore,
it
is
necessary
develop
tools
study
and
the
signaling
pathways
they
control.
This
Review
broadly
describes
molecular
approaches
that
enable
1)
visualization
of
determine
localization
distribution;
2)
sensing
receptor
activation
permanent
readouts
as
well
in
real
time;
3)
perturbing
activity
mimicking
receptor-controlled
learn
more
about
these
processes.
Together,
have
provided
valuable
insight
into
fundamental
biology
helped
characterize
therapeutics
target
receptors.
Medicinal Research Reviews,
Journal Year:
2025,
Volume and Issue:
unknown
Published: April 3, 2025
ABSTRACT
Adrenoceptors
(ARs)
play
a
vital
role
in
various
physiological
processes
and
are
key
therapeutic
targets.
The
advent
of
optical
control
techniques,
including
optogenetics
photopharmacology,
offers
the
potential
to
modulate
AR
signaling
with
precise
temporal
spatial
resolution.
In
this
review,
we
summarize
latest
advancements
signaling,
encompassing
optogenetics,
photocaged
compounds,
photoswitchable
compounds.
We
also
discuss
limitations
current
tools
provide
an
outlook
on
next
generation
optogenetic
photopharmacological
tools.
These
emerging
technologies
not
only
enhance
our
understanding
but
pave
way
for
developments.
Current Opinion in Pharmacology,
Journal Year:
2022,
Volume and Issue:
66, P. 102266 - 102266
Published: July 20, 2022
Metabotropic
glutamate
receptors
(mGlu)
are
a
family
of
class
C
G
protein-coupled
(GPCRs)
with
important
biological
functions
and
widespread
expression.
The
mechanisms
mGlu
activation
the
development
allosteric
modulators
for
these
dimeric
proteins
have
attracted
singular
attention
including
use
light
regulated
ligands.
Photopharmacology
involves
integration
photoactive
moiety
into
ligand
structure
that
following
specific
illumination
undergoes
structural
rearrangement
changes
its
activity.
light-regulated
ligands
offers
opportunity
to
manipulate
signalling
spatiotemporal
precision,
unattainable
classical
pharmacological
approaches.
In
this
review,
we
will
discuss
some
innovations
been
made
in
photopharmacology
date.
We
prospects
molecular
tools
control
mGluRs
new
perspectives
understanding
mechanisms,
pharmacology
(patho)physiology
can
ultimately
result
innovative
drug
discovery
concepts.
Chemistry - A European Journal,
Journal Year:
2022,
Volume and Issue:
28(63)
Published: July 28, 2022
Photoswitchable
ligands
as
biological
tools
provide
an
opportunity
to
explore
the
kinetics
and
dynamics
of
clinically
relevant
μ-opioid
receptor.
These
can
potentially
activate
or
deactivate
receptor
when
desired
by
using
light.
Spatial
temporal
control
activity
allows
for
application
in
a
diverse
range
investigations.
have
been
developed
this
work,
modelled
on
known
agonist
fentanyl,
with
aim
expanding
current
"toolbox"
fentanyl
photoswitchable
ligands.
In
doing
so,
that
change
geometry
(isomerize)
upon
exposure
light,
varying
photophysical
biochemical
properties.
This
variation
properties
could
be
valuable
further
studying
functional
significance
