ChemMedChem,
Journal Year:
2024,
Volume and Issue:
19(22)
Published: Sept. 20, 2024
Mycobacteria
are
opportunistic
intracellular
pathogens
that
have
plagued
humans
and
other
animals
throughout
history
still
today.
They
manipulate
hijack
phagocytic
cells
of
immune
systems,
enabling
them
to
occupy
this
peculiar
infection
niche.
exploit
a
plethora
mechanisms
resist
antimicrobials
(e.
g.,
waxy
cell
walls,
efflux
pumps,
target
modification,
biofilms,
etc.)
thereby
evolving
into
superbugs,
such
as
extensively
drug-resistant
tuberculosis
(XDR
TB)
bacilli
the
emerging
pathogenic
Mycobacterium
abscessus
complex.
This
review
summarizes
action
some
surging
antimycobacterial
strategies.
Exploiting
fact
mycobacteria
obligate
aerobes
differences
between
their
oxidative
phosphorylation
pathways
versus
human
counterpart
opens
promising
avenue
for
drug
discovery.
The
polymorphism
respiratory
complexes
across
mycobacterial
imposes
challenges
on
repositioning
agents
battle
rise
in
nontuberculous
infections.
In
silico
strategies
exploiting
machinery
data
design
novel
therapeutic
touched
upon.
potential
druggability
elements
is
reviewed.
Future
research
addressing
health
associated
with
discussed.
Biologie Aujourd hui,
Journal Year:
2024,
Volume and Issue:
218(1-2), P. 41 - 54
Published: Jan. 1, 2024
The
review
is
focused
on
recent
drug
discovery
advances
based
targeted
protein
degradation
strategies.
This
new
area
of
research
has
exploded
leading
to
the
development
potential
drugs
useful
in
a
large
variety
human
diseases.
They
first
target
disease
relevant
proteins
difficult
counteract
with
other
classical
strategies
and
extend
now
aggregates,
organelles,
nucleic
acids
or
lipidic
droplets.
These
degraders
engaged
either
ubiquitin-proteasome
system
for
PROTACs
molecular
glues
(first
generation),
lysosomal
via
endosome-lysosome
(LYTACs)
autophagy-lysosome
(ATTEC,
AUTAC,
AUTOTAC)
(following
generations
degraders).
have
expanded
from
orthodox
heterobifunctional
ones
derivatives
such
as
homo-PROTACs,
pro-PROTACs,
CLIPTACs,
HaloPROTACs,
PHOTOTACs,
Bac-PROTACs,
AbTACs,
ARN-PROTACs.
small
molecular-weight
induce
formation
ternary
complexes
which
implicate
an
ubiquitin
ligase
E3
allowing
ubiquinitation
followed
by
its
proteasomal
degradation.
Lysosomal
(LYTAC,
ATTEC,
specifically
recognize
extracellular
membrane
dysfunctional
organelles
transport
them
into
lysosomes
where
they
are
degraded.
overcome
limitations
observed
degradations
induced
PROTAC
demonstrate
their
treat
diseases,
especially
neurodegenerative
ones.
Pharmaceutical
companies
at
world
level
develop
these
targeting
cancers,
immuno-inflammatory
diseases
well
Efficiency
risks
novel
therapeutic
discussed.
ChemMedChem,
Journal Year:
2024,
Volume and Issue:
19(22)
Published: Sept. 20, 2024
Mycobacteria
are
opportunistic
intracellular
pathogens
that
have
plagued
humans
and
other
animals
throughout
history
still
today.
They
manipulate
hijack
phagocytic
cells
of
immune
systems,
enabling
them
to
occupy
this
peculiar
infection
niche.
exploit
a
plethora
mechanisms
resist
antimicrobials
(e.
g.,
waxy
cell
walls,
efflux
pumps,
target
modification,
biofilms,
etc.)
thereby
evolving
into
superbugs,
such
as
extensively
drug-resistant
tuberculosis
(XDR
TB)
bacilli
the
emerging
pathogenic
Mycobacterium
abscessus
complex.
This
review
summarizes
action
some
surging
antimycobacterial
strategies.
Exploiting
fact
mycobacteria
obligate
aerobes
differences
between
their
oxidative
phosphorylation
pathways
versus
human
counterpart
opens
promising
avenue
for
drug
discovery.
The
polymorphism
respiratory
complexes
across
mycobacterial
imposes
challenges
on
repositioning
agents
battle
rise
in
nontuberculous
infections.
In
silico
strategies
exploiting
machinery
data
design
novel
therapeutic
touched
upon.
potential
druggability
elements
is
reviewed.
Future
research
addressing
health
associated
with
discussed.
