Development
of
a
new
Ca2+
/
calmodulin
antagonist
and
its
anti-proliferative
activity
against
colorectal
cancer
cells
.
We
previously
identified
a
cellular
target
of
a
cell
cycle
inhibitor
HBC
as
Ca(2+)
/
calmodulin
(
Ca(2+)
/
CaM
)
through
chemical
genetics
approach
.
Using
the
mechanism
-
based
drug
design
,
we
developed
a
new
Ca(2+)
/
CaM
antagonists
based
on
the
structure
of
HBC
.
The
compound
,
(4-{3,5-bis-[2-(4-hydroxy-3-methoxy-phenyl)-vinyl]-4,5-dihydro-pyrazol-1-yl}-phenyl)-(4-methyl-piperazin-1-yl)-methanone
(
referred
as
HBCP
)
,
binds
to
Ca(2+)
/
CaM
in
vitro
and
inhibits
the
proliferation
of
HCT15
colon
cancer
cells
.
HBCP
induced
sustained
phosphorylation
of
ERK1
/
2
and
subsequently
activated
p21(WAF1)
expression
in
HCT15
cells
.
Moreover
,
HBCP
reversibly
induced
the
G(0)
/
G(1)
cell
cycle
arrest
in
the
cells
.
These
data
demonstrate
that
HBCP
is
a
new
potent
Ca(2+)
/
CaM
antagonist
and
can
be
applied
for
CaM
related
therapeutic
uses
.