Signal Transduction and Targeted Therapy,
Год журнала:
2025,
Номер
10(1)
Опубликована: Март 5, 2025
The
successful
approval
of
peptide-based
drugs
can
be
attributed
to
a
collaborative
effort
across
multiple
disciplines.
integration
novel
drug
design
and
synthesis
techniques,
display
library
technology,
delivery
systems,
bioengineering
advancements,
artificial
intelligence
have
significantly
expedited
the
development
groundbreaking
drugs,
effectively
addressing
obstacles
associated
with
their
character,
such
as
rapid
clearance
degradation,
necessitating
subcutaneous
injection
leading
increasing
patient
discomfort,
ultimately
advancing
translational
research
efforts.
Peptides
are
presently
employed
in
management
diagnosis
diverse
array
medical
conditions,
diabetes
mellitus,
weight
loss,
oncology,
rare
diseases,
additionally
garnering
interest
facilitating
targeted
platforms
advancement
vaccines.
This
paper
provides
an
overview
present
market
clinical
trial
progress
therapeutics,
platforms,
It
examines
key
areas
through
literature
analysis
emphasizes
structural
modification
principles
well
recent
advancements
screening,
design,
technologies.
accelerated
including
peptide-drug
complexes,
new
vaccines,
innovative
diagnostic
reagents,
has
potential
promote
era
precise
customization
disease
therapeutic
schedule.
Nature Metabolism,
Год журнала:
2024,
Номер
6(2), С. 290 - 303
Опубликована: Фев. 5, 2024
Abstract
Obesity
is
a
major
public
health
crisis.
Multi-specific
peptides
have
emerged
as
promising
therapeutic
strategies
for
clinical
weight
loss.
Glucagon-like
peptide-1
(GLP-1)
and
glucose-dependent
insulinotropic
polypeptide
(GIP)
are
endogenous
incretins
that
regulate
through
their
receptors
(R).
AMG
133
(maridebart
cafraglutide)
bispecific
molecule
engineered
by
conjugating
fully
human
monoclonal
anti-human
GIPR
antagonist
antibody
to
two
GLP-1
analogue
agonist
using
amino
acid
linkers.
Here,
we
confirm
the
GLP-1R
activities
in
cell-based
systems
report
ability
of
reduce
body
improve
metabolic
markers
male
obese
mice
cynomolgus
monkeys.
In
phase
1,
randomized,
double-blind,
placebo-controlled
study
participants
with
obesity
(
NCT04478708
),
had
an
acceptable
safety
tolerability
profile
along
pronounced
dose-dependent
multiple
ascending
dose
cohorts,
loss
was
maintained
up
150
days
after
last
dose.
These
findings
support
continued
evaluation
133.
Nature Metabolism,
Год журнала:
2023,
Номер
5(6), С. 945 - 954
Опубликована: Июнь 5, 2023
Abstract
The
incretins
glucose-dependent
insulinotropic
polypeptide
(GIP)
and
glucagon-like
peptide
1
(GLP-1)
mediate
insulin
responses
that
are
proportionate
to
nutrient
intake
facilitate
glucose
tolerance
.
GLP-1
receptor
(GLP-1R)
is
an
established
drug
target
for
the
treatment
of
diabetes
obesity
2
,
whereas
therapeutic
potential
GIP
(GIPR)
a
subject
debate.
Tirzepatide
agonist
at
both
GIPR
GLP-1R
highly
effective
type
3,4
However,
although
tirzepatide
activates
in
cell
lines
mouse
models,
it
not
clear
whether
or
how
dual
agonism
contributes
its
benefit.
Islet
beta
cells
express
GIPR,
secretion
mechanism
by
which
incretin
agonists
improve
glycemic
control
5
Here,
we
show
islets,
stimulates
predominantly
through
GLP-1R,
owing
reduced
potency
GIPR.
human
antagonizing
activity
consistently
decreases
response
tirzepatide.
Moreover,
enhances
glucagon
somatostatin
islets.
These
data
demonstrate
islet
hormone
from
islets
receptors.
Nature Medicine,
Год журнала:
2024,
Номер
30(7), С. 2037 - 2048
Опубликована: Июнь 10, 2024
Abstract
Retatrutide
is
a
novel
triple
agonist
of
the
glucose-dependent
insulinotropic
polypeptide,
glucagon-like
peptide
1
and
glucagon
receptors.
A
48-week
phase
2
obesity
study
demonstrated
weight
reductions
22.8%
24.2%
with
retatrutide
8
12
mg,
respectively.
The
primary
objective
this
substudy
was
to
assess
mean
relative
change
from
baseline
in
liver
fat
(LF)
at
24
weeks
participants
that
metabolic
dysfunction-associated
steatotic
disease
≥10%
LF.
Here,
randomized,
double-blind,
placebo-controlled
trial,
(
n
=
98)
were
randomly
assigned
48
once-weekly
subcutaneous
(1,
4,
or
mg
dose)
placebo.
LF
−42.9%
(1
mg),
−57.0%
(4
−81.4%
(8
−82.4%
(12
mg)
+0.3%
(placebo)
(all
P
<
0.001
versus
placebo).
At
weeks,
normal
(<5%)
achieved
by
27%
52%
79%
86%
0%
participants.
significantly
related
changes
body
weight,
abdominal
measures
associated
improved
insulin
sensitivity
lipid
metabolism.
ClinicalTrials.gov
registration
NCT04881760
.
Diabetologia,
Год журнала:
2023,
Номер
66(10), С. 1796 - 1808
Опубликована: Май 20, 2023
Abstract
Glucagon-like
peptide-1
(GLP-1)
receptor
agonists
are
established
pharmaceutical
therapies
for
the
treatment
of
type
2
diabetes
and
obesity.
They
mimic
action
GLP-1
to
reduce
glucose
levels
through
stimulation
insulin
secretion
inhibition
glucagon
secretion.
also
body
weight
by
inducing
satiety
central
actions.
The
used
clinically
based
on
exendin-4
native
available
as
formulations
daily
or
weekly
s.c.
oral
administration.
agonism
is
achieved
inhibitors
dipeptidyl
peptidase-4
(DPP-4),
which
prevent
inactivation
glucose-dependent
insulinotropic
polypeptide
(GIP),
thereby
prolonging
their
raised
after
meal
ingestion.
Other
developments
in
include
formation
small
orally
compounds
with
potential
pharmaceutically
stimulate
from
gut.
In
addition,
GLP-1/glucagon
GLP-1/GIP
dual
GLP-1/GIP/glucagon
triple
have
shown
blood
effects
islets
peripheral
tissues,
improving
beta
cell
function
stimulating
energy
expenditure.
This
review
summarises
gut
hormone-based
presents
future
outlook
use
Graphical
Circulation Research,
Год журнала:
2024,
Номер
135(1), С. 174 - 197
Опубликована: Июнь 20, 2024
GPCRs
(G
protein-coupled
receptors),
also
known
as
7
transmembrane
domain
receptors,
are
the
largest
receptor
family
in
human
genome,
with
≈800
members.
regulate
nearly
every
aspect
of
physiology
and
disease,
thus
serving
important
drug
targets
cardiovascular
disease.
Sharing
a
conserved
structure
comprised
α-helices,
couple
to
heterotrimeric
G-proteins,
GPCR
kinases,
β-arrestins,
promoting
downstream
signaling
through
second
messengers
other
intracellular
pathways.
development
has
led
therapies,
such
antagonists
β-adrenergic
angiotensin
II
receptors
for
heart
failure
hypertension,
agonists
glucagon-like
peptide-1
reducing
adverse
events
emerging
indications.
There
continues
be
major
interest
cardiometabolic
driven
by
advances
mechanistic
studies
structure-based
design.
This
review
recounts
rich
history
research,
including
current
state
clinically
used
drugs,
highlights
newly
discovered
aspects
biology
promising
directions
future
investigation.
As
additional
mechanisms
regulating
uncovered,
new
strategies
targeting
these
ubiquitous
hold
tremendous
promise
field
medicine.
