Pharmacological Reviews,
Journal Year:
2024,
Volume and Issue:
76(3), P. 414 - 453
Published: March 15, 2024
Since
its
discovery
over
35
years
ago,
MDM2
has
emerged
as
an
attractive
target
for
the
development
of
cancer
therapy.
MDM29s
activities
extend
from
carcinogenesis
to
immunity,
response
various
therapies.
report
first
inhibitor
more
than
30
approaches
inhibit
have
been
attempted,
with
hundreds
small
molecule
inhibitors
evaluated
in
preclinical
studies
and
numerous
molecules
tested
clinical
trials.
Although
many
degraders
trials,
there
is
currently
no
FDA-approved
on
market.
Nevertheless,
are
several
current
trials
promising
agents
that
may
overcome
past
failures,
including
granted
FDA
orphan
drug
or
fast-track
status.
We
herein
summarize
research
efforts
discover
develop
inhibitors,
focusing
those
induce
degradation
exert
anticancer
activity,
regardless
p53
status
cancer.
also
describe
how
investigations
moved
towards
combining
other
agents,
immune
checkpoint
inhibitors.
Finally,
we
discuss
challenges
future
directions
accelerate
application
In
conclusion,
targeting
remains
a
treatment
approach,
protein
represents
novel
strategy
downregulate
without
side
effects
existing
blocking
p53-MDM2
binding.
Additional
needed
finally
realize
full
potential
inhibition
treating
chronic
diseases
where
implicated.
Significance
Statement
Overexpression/amplification
oncogene
detected
human
cancers
associated
disease
progression,
resistance,
poor
patient
outcomes.
Herein,
review
previous,
emerging
MDM2-targeted
therapies
chemotherapy
immunotherapy
regimens.
The
findings
these
contemporary
lead
safer
effective
treatments
patients
overexpressing
MDM2.
Letters in Drug Design & Discovery,
Journal Year:
2022,
Volume and Issue:
21(3), P. 480 - 495
Published: Sept. 23, 2022
Abstract:
Molecular
docking
is
a
structure-based
computational
method
that
generates
the
binding
pose
and
affinity
between
ligands
targets.
There
are
many
powerful
programs.
However,
there
no
single
program
suitable
for
every
system.
Hence,
an
appropriate
chosen
based
on
availability,
need,
computer
capacity.
has
clear
steps
should
be
followed
carefully
to
get
good
result.
:
applications
at
various
stages
in
drug
discovery.
Although
it
application
areas,
commonly
applied
virtual
screening
repurposing.
As
result,
playing
substantial
role
endeavor
discover
potent
against
COVID-19.
also
approved
drugs
pharmaceutical
market
developed
through
use
of
molecular
docking.
accessible
data
increasing
advancing
with
contribution
latest
developments,
its
discovery
increasing.
played
crucial
making
faster,
cheaper,
more
effective.
More
advances
algorithms,
integration
other
methods,
introduction
new
approaches
expected.
Thus,
will
make
easier
Patterns,
Journal Year:
2023,
Volume and Issue:
4(2), P. 100678 - 100678
Published: Feb. 1, 2023
Molecular
discovery
is
a
multi-objective
optimization
problem
that
requires
identifying
molecule
or
set
of
molecules
balance
multiple,
often
competing,
properties.
Multi-objective
molecular
design
commonly
addressed
by
combining
properties
interest
into
single
objective
function
using
scalarization,
which
imposes
assumptions
about
relative
importance
and
uncovers
little
the
trade-offs
between
objectives.
In
contrast
to
Pareto
does
not
require
knowledge
reveals
However,
it
introduces
additional
considerations
in
algorithm
design.
this
review,
we
describe
pool-based
de
novo
generative
approaches
with
focus
on
algorithms.
We
show
how
relatively
direct
extension
Bayesian
plethora
different
models
extend
from
single-objective
similar
ways
non-dominated
sorting
reward
(reinforcement
learning)
select
for
retraining
(distribution
propagation
(genetic
algorithms).
Finally,
discuss
some
remaining
challenges
opportunities
field,
emphasizing
opportunity
adopt
techniques
Pharmacological Reviews,
Journal Year:
2024,
Volume and Issue:
76(3), P. 414 - 453
Published: March 15, 2024
Since
its
discovery
over
35
years
ago,
MDM2
has
emerged
as
an
attractive
target
for
the
development
of
cancer
therapy.
MDM29s
activities
extend
from
carcinogenesis
to
immunity,
response
various
therapies.
report
first
inhibitor
more
than
30
approaches
inhibit
have
been
attempted,
with
hundreds
small
molecule
inhibitors
evaluated
in
preclinical
studies
and
numerous
molecules
tested
clinical
trials.
Although
many
degraders
trials,
there
is
currently
no
FDA-approved
on
market.
Nevertheless,
are
several
current
trials
promising
agents
that
may
overcome
past
failures,
including
granted
FDA
orphan
drug
or
fast-track
status.
We
herein
summarize
research
efforts
discover
develop
inhibitors,
focusing
those
induce
degradation
exert
anticancer
activity,
regardless
p53
status
cancer.
also
describe
how
investigations
moved
towards
combining
other
agents,
immune
checkpoint
inhibitors.
Finally,
we
discuss
challenges
future
directions
accelerate
application
In
conclusion,
targeting
remains
a
treatment
approach,
protein
represents
novel
strategy
downregulate
without
side
effects
existing
blocking
p53-MDM2
binding.
Additional
needed
finally
realize
full
potential
inhibition
treating
chronic
diseases
where
implicated.
Significance
Statement
Overexpression/amplification
oncogene
detected
human
cancers
associated
disease
progression,
resistance,
poor
patient
outcomes.
Herein,
review
previous,
emerging
MDM2-targeted
therapies
chemotherapy
immunotherapy
regimens.
The
findings
these
contemporary
lead
safer
effective
treatments
patients
overexpressing
MDM2.
