THE SCRIPPS
RESEARCH INSTITUTE
and
UNIVERSITY OF CALIFONNIA
SAN DIEGO
HOI.D FOR SCTENCE EMBARGO:
Broadcast -- 3 p.m. Pacific
Time, Thursday,
-- Friday,
Print
YIay 22, L992
Media Contacts:
Warren R. Froelich,
Sue Pondrom, TSRI,
May 21,
L992
UCSD, (6L9) 534-8564
(6L9) 554-8290
IITROi'AII ITORSEII ANTI-CANCER AGENTS
DESIGNED AND SYNTHESIZED BY IJA JOIJIJA SCIENTTSTS
CA 3 prn May 21,
La JoIIa,
that
represents
tested
from
some of
The Scripps
California,
The molecules,
also
called
located
cells
while
rrProvided
their
selectivity
cells
humans,
can be maintained
these
cancer, rr the
journal
leaving
molecules
scientists
of
the
and the
La Jolla,
in
healthy
against
cells
and enhanced
in
may emerge as powerful
wrote
American
in
the
current
Association
for
scientists
University
of
een dye ines),
their
tumor
ever
California.
(pronounced
selectivitytt
cancer
normal
in
enediynes
have shown rrremarkable
destroy
the
both
agents
by a team of
(TSRI)
Institute
of molecules
anti-cancer
and synthesized
Research
San Diego,
A new class
most potent
the
has been designed
1-992 --
ability
to
intact.
cells
versus
animal
models
drugs
issue
the
and
against
of
science,
Advancement
of
Science.
K.C. Nicolaou,
and chairman,
professor
of
Department
chemistry,
cornpounds because
of
their
afe
of
studies
required
TSRI's Darlene
Chemistry,
said
as well
rrwe are really
potency,
but
most
Shiley
Professor
as a UCSD
excited
about
importantly,
these
because
tt
the
study's
to
assure
before
who is
of
their
selectivity.
Nicolaou,
further
Ph.D.,
it
principal
the
investigator,
molecule's
can be tested
(more)
in
safety
patients.
cautioned
that
and effectiveness
2 --
Page
- 3 pm May 21-;
EMBARGOED:Broadcast
Print
VIay 22
TSRI/UCSD
The studyts
Ph.D.;
Virginia
Ph.D.,
all
co-authors
A. Estevez,
from The Scripps
The new molecules
occurring
toxins
to
themselves
defend
chemicals
are
international
companies
are
isolated
in
chemicals
called
DNA, the
helically
the
was real.
three
--
in
domains
that,
enediyne;
a delivery
the
researchers
describes
attach
break
the
the
rrwarheadrr that
and drug
as their
first
highly
themselves
to
of heredity,
it
reactive
the
cell's
--
and then
at
pieces.
into
member of
the
so diaborical,
a cascade
Science
houses
system that
of
paper,
enediyne
r couldn't
each molecule
when combined,
and a triggering
initiates
these
family,
believe
rl
molecular
target;
use chemicals
have attracted
work by creating
that
rrrt looked
As described
with
that
tt
molecules
to
recalled,
naturally
By definition,
molecules
activity.
signal
of
bacteria
bacteria.
shaped repository
When introduced
it
versions
unique
these
radicals
appropriate
Nicoraou
synthetic
by what Nicolaou
the
Susan C. Tsay,
and Wolfgang W. Wrasidlo,
among academic
rrphenomenal biological
Ph.D.;
antibiotics.
1987,
intrigued
Dai,
Research Institute.
from other
attention
essence,
Ph.D.;
from
considered
Discovered
In
are Wei-tt.
the
directs
device
that,
reactions
that
a potent
create
active
dt
region
of
the
molecule
the
right
leads
is
to
equipped
weapon:
a
the
to
its
signal,
the
generation
of
DNA damaging molecules.
rrYou could
mythology,"
said
compare this
single-
destroy
and double-strand
to
a tTrojan
rrThe rnolecules
Nico1aou.
and upon activation,
process
the
genetic
DNA cuts.rl
(nore)
enter
material
horse,
the
via
of
cell
both
Greek
intact
3 --
Page
Although
the
ilremarkablerr
naturally
anti-cancer
between healthy
cells
synthesized
versions
chemists
take
while
- 3 pm lvlay 21,
EMBARGOED:Broadcast
Print
l{,ay 22
TSRI/UCSD
to
leaving
During
of
cells
to
the
on the
they
cells.
had to
potent
the
mimic
the
differentiate
the
be designed
anti-cancer
action
and we are
Nicolaou
by the
activity,
of
these
trying
to
them in
the
molecules
by
make thern as
laboratory
in
said.
of years,
couple
naturally
to
To be useful,
so we can produce
last
fail
have shown
intact.
TSRI and UCSD have designed
based
molecules
molecules
own warheads,
quantiti€srtt
large
the
advantage
as possible
simple
and tumor
healthy
our
activity,
of
rrWe are trying
designing
occurring
Nicolaours
and synthesized
occurring
labs
several
compounds,
with
at
both
molecules
a few
rnodif ications.
In
with
the
paper,
Science
a synthetic
version
dyneniciD
A, which
naturally
by bacteria
exploring
mimics
models
In
with
of
these
chemical
groups
some cases,
one of
warhead,
to
to
aid
found
AIso
in
with
devices
pr.oduced
ItAlthough
soil.
rnolecules
a molecular
designed
subsequent
the
are
we concentrated
synthetic
combined
that
called
into
the
attachment
wetre
on dynemicin
to make, rr Nicolaou
easiest
allow
in
experiments
antibiotic
enediynes
enediynes,
lock.
detection
four
the
described
anti-cancer
originally
experiments,
devices,
researchers
the
are the
and built-in
tethering
of
other
because they
a modified
device
is
the
said.
were designed
triggering
molecule
of
were
other
delivery
of
the
molecule;
designed
to
help
monitor
and,
the
results.
rrOur molecules
proved
to
be more potent
(rnore)
than
the
naturally
in
Page
4 --
occurring
substances
The studies
than
- 3 pm May 21
EMBARGOED:Broadcast
Print
l{ay 22
TSRI/UCSD
in
test
further
agents
vinblastine
and bleomycin,
promising
and much-discussed
rrdramatic
anti-cancer
agent
certain
leukemia
cells,
animals.
the
killing
without
existence
than
the
highly
known as taxol.
molecules
showed
types
destroying
of
tumor
normal
cells,
cells,
vs.
by these
plus
clinical
biological
within
cornpounds is
because
it
the
cell
but
we're
low
makes these
development,
team at
their
rr added
TSRI.
that
opens up the
quite
not
lock
yet
sure
what
said.
explanations
preferentially;
might
factors
differences
these
these
a real
for
tumor-associated
membranes to
of
mechanisrn),
possible
of
the
happens
Nicolaou
Three
is
candidates
triggering
isrtt
feature
This
head of
I'something
healthy
and even more potent
in
in
Wrasidlo,
cells
doxorubicin,
selectivitiestt
new aglents prime
that
cis-platin,
added.
toxicity
the
be more potent
the
rrA most remarkable
(of
including
said.
to
molecules
amounts of
particularly
Nicolaou
small
rr Nicolaou
studies,
showed the
known anti-cancer
Surprisingly,
tube
in
be:
that
ceII
machinery
to
potential
rnight
activate
permeability
the
cornpoundsl differences
cancerous
the
in
the
repair
these
of
ability
of
the
DNA damage caused
agents.
Nicolaou
said
he and his
of
out which,
if
any,
atternpting
to
design
or DNA sequences
these
research
explanations
a delivery
responsible
team are trying
system
for
cancer.
###
is
to
correct.
home in
to
find
He is
also
on turnor
cells