AU  Jones CD
AU Blaszczak LC
AU Goettel ME
AU Suarez T
AU Crowell TA
AU Mabry TE
AU Ruenitz PC
AU Srivatsan V
TI Antiestrogens. 3. Estrogen receptor affinities and antiproliferative effects
in MCF-7 cells of phenolic analogues of trioxifene, [3,4-dihydro-2 - (4-
methoxyphenyl)-1-naphthalenyl][4-[2-(1-pyrrolidinyl)ethoxy]-
phenyl]methanone.
SO Journal of medicinal chemistry SOJ Med Chem SO1992 Mar 6;35(5):931-8.
AB Benzothiophenes 3 and 4, derived from the acrylophenone antiestrogen
trioxifene (2), are characterized by high estrogen receptor (ER) affinity
and low residual estrogenicity compared to tamoxifen (1a). In order to
characterize further the growth suppression mechanism for these structural
types we have prepared structural variants of 2 bearing hydroxy groups
positioned to maximize ER affinity. Thus, dihydronaphthalenes 5 and 6 and
benzofluorenes 7 and 8 were prepared and studied in MCF-7 human breast
cancer cells, in comparison with 3 and 4. All compounds were powerful
suppressants of cell growth, with 50% inhibition ranging from 4.5 to 160 nM.
Greatest potency was seen with diphenols 6 and 8. These compounds had
intracellular ER affinities ranging from 0.2 to 4.1% of that of estradiol,
suggestive of a potential for partial agonist effects. Simultaneous exposure
of cells to 0.1 microM concentrations of estradiol and 3 or 4 did  not
affect the degree of growth inhibition seen with 0.1 microM 3 or 4 alone.
Partial reversal of inhibition occurred when 0.1 microM 5-8 were each
accompanied by 0.1 microM estradiol. Under these conditions complete
reversal of growth inhibition has been found with 1a, 1b, and other
triarylethylenes. Calmodulin, a putative target for triarylethylenes, and
which is antagonized by 1a, was shown to interact weakly with 7 and 8 and
not at all with 3-6. These results suggest that MCF-7 cell growth
suppression by 3-8 may be due to interaction with unidentified receptors
besides ER and extend earlier findings indicating that events occurring
after interaction of these compounds with ER differ from those of
triarylethylene antiestrogens.

AU Shah IG
AU Parsons DL
TI Human albumin binding of tamoxifen in the presence of a perfluorochemical
erythrocyte substitute.
SO Journal of pharmacy and pharmacology SOJ Pharm Pharmacol SO1991
Nov;43(11):790-3.
AB The binding of tamoxifen (an HSA site IV ligand) to human serum albumin
(HSA) in the presence of a perfluorochemical (PFC) erythrocyte substitute
has been examined. Standard centrifugation followed by supernatant
ultrafiltration was used to study the binding of 0.1 and 0.5 microgram mL-1
tamoxifen at ambient conditions. Tamoxifen was extensively bound (greater
than 99%) to the PFC emulsion through an association with the emulsifiers of
the droplets. Tamoxifen was also extensively bound (greater  than 99%) to
HSA. The percent free tamoxifen increased upon HSA dilution. Tamoxifen was
extensively bound by various mixtures of HSA and the PFC emulsion and the
percent free drug was similar to those obtained with HSA alone. However, the
position of drug binding (PFC emulsion vs HSA) varied significantly with
changes in the ratio of PFC emulsion to HSA. This could  be important in
terms of the different distribution of HSA and PFC emulsion in the body.
Studies with PFC emulsion components indicated that any displacement of
HSA-bound tamoxifen by the PFC emulsion was due to the  oleic acid and, to a
much smaller degree, Pluronic F-68 components. Other HSA site IV ligands are
expected to be similarly displaced.

AU Enevoldson TP
AU Harding AE
TI Improvement in the POEMS syndrome after administration of tamoxifen [letter]
SO Journal of neurology, neurosurgery and psychiatry SOJ Neurol Neurosurg
Psychiatry SO1992 Jan;55(1):71-2.