Antitumor Steroids
445
S
CF
2
CF
3
O
OH
HO
7
a
ICI 182,780 (fulvestrant)
C
N
OH
HO
7
a
ICI 164,384
O
CH
3
OH
O
S
CF
2
CF
3
11
b
O
O
RU 58,668
HO
Fig. 5
Chemical formulas of pure antiestrogens.
through a long alkyl side chain intended to
protrude out of the HBD when bound to
the receptor (as the side chain of OH-Tam
and related SERMs). The resulting confor-
mational state of the receptor is, however,
slightly different from that elicited by all
investigated SERMs, although their long
alkyl side chain similarly abrogate the
alignment of H-12 onto the steroidal core.
3
Restrictive Conditions for Ef±cient
Targeting of Antitumor Estrogens
To utilize steroid hormones as effective
delivery vector of cytotoxic drugs to the
tumor cells, several conditions should
be satisFed. Concerning the association
of the compounds with their receptors,
we stress
the need for
the
following
four conditions:
1. It is important to link the cytotoxic
agent in such a way as to not interfere
with the recognition of the steroidal
vector.
2. The cytotoxic moiety should be shipped
to its target. Since receptors focal-
ize their action at the genomic level,
d
rug
stob
el
ink
edtoth
es
t
e
ro
ida
r
e
restricted to those producing damage
at the DNA level or associated nu-
clear proteins.
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