IUBio

<Q> Isomers of Tamoxifen

The Leukotomist np07la at mail.telepac.pt
Tue May 7 10:54:49 EST 1996


hiroya at cryo.affrc.go.jp (Hiroya Kadokawa) wrote:

>Will you tell me the answer for my question?

>How much more potent, as the estrogen recepor antagonist, the (z) isomer
>of Tamoxifen is over the (E) isomer?

Actually, tamoxifen, which is an antiestrogen derived from a stilbene
nucleus, can display either agonist or antagonist activity depending
on the orientation of the alkylaminoethoxy side chain. Indeed, the
trans (E) conformation tamoxifen is an antiestrogen, and that in the
cis (Z) conformation it is an agonist. In humans, both stereoisomers
can be activated metabolically by hydroxylation at C4 of the A ring,
producing phenolic metabolites with affinities for the estrogen
receptor that are 100-fold greater than those of the parent
molecules. Although the stereoisomers of tamoxifen are relatively
stable, their phenolic metabolites isomerize readily to produce
racemic mixtures. This explains why antiestrogenic properties observed
in vivo do not always agree with those detected in vitro. Tamoxifen is
marketed as the trans (E) isomer.

>And will you tell me the scientific papers including the answer?

Jordan VC, Mittal S, Gosden B, Koch R, Lieberman ME.
Structure-activity relationship of estrogens. Environ. Health
Perspect., 1985, 6, 59-79.

Katzenellenbogen JA, Carlson KE, Katzenellenbogen BS. Facile geometric
isomerization of phenolic non-steroidal estrogens and antiestrogens:
limitations to the interpretation of experiments characterizing the
activity of individual isomers. J. Steroid Biochem., 1988, 22,
589-596.

Miquel JF, Gilbert J. A chemical classification of nonsteroidal
antagonists of sex-steroid hormone action. J. Steroid Biochem., 1988,
31, 525-544.



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             8888888888888888888888888888	Sergio Miguel Cardoso
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