Disease relevance of RU 58 668

• Taken together, these results suggest a promising usefulness for RU 58668 in the treatment of metastatic breast cancer in women [1].
• Improved antitumoral properties of pure antiestrogen RU 58668-loaded liposomes in multiple myeloma [2].
• Our results show that RU 58668 blocked estrogen's suppressive effects on feeding behavior and body weight [3].
• Pure antiestrogen RU 58668-loaded nanospheres: morphology, cell activity and toxicity studies [4].

High impact information on RU 58 668

• No difference was observed in the fate of ER whether bound to pure antiestrogens ICI 182,780 or RU 58668 [5].
• Interaction and dissociation by ligands of estrogen receptor and Hsp90: the antiestrogen RU 58668 induces a protein synthesis-dependent clustering of the receptor in the cytoplasm [6].
• Thus, several biodegradable drug delivery systems containing either "mixed" (4-hydroxytamoxifen - 4-HT) or "pure" (RU 58668 - RU) AEs were prepared [7].
• In most of multiple myeloma (MM) cells, the "pure" antiestrogen (AE) RU 58668 (RU) induced either a G1-arrest (LP-1, OPM-2, NCI-H929, U266 cells) or apoptosis (RPMI 8226 cells) [2].
• On the other hand, we did not find that blocking estrogen receptors with RU 58668 inhibited the restoration of copulatory behavior or partner preference in testosterone-treated gonadectomized male rats, even though the level of brain nuclear estrogen receptor occupation was significantly reduced to the level found in gonadectomized males [8].

Chemical compound and disease context of RU 58 668

• The purpose of this study was to test if RU 58668 blocks two classic estrogen-dependent behaviors: female sexual behavior and feeding behavior [3].

Biological context of RU 58 668

• In vitro, 1 nM RU 58668 induced an accumulation of MCF-7 cells in G0/G1 phases of the cell cycle within 48 h and, in contrast to trans-4-hydroxy-tamoxifen, blocked the invasiveness of ras-transfected MCF-7 cells into the chick embryo heart during the three weeks of co-culture [1].
• However, the kinetics of these degradations are slower than those induced by the selective estrogen receptor down-regulator RU 58668 (RU) [9].
• Interestingly, ligands able to down-regulate ER (i.e. E2 or RU 58 668) increased ER phosphorylation while 4-OH-TAM which up-regulate the receptor had little effect in this regard [10].
• Effects of the antiestrogen, RU 58668, on female sexual behavior in rats [3].

Anatomical context of RU 58 668

• The known ability of these ligands to stabilize ER in the cell nucleus before regulating ER level may explain this phenomenon since such antagonism was not recorded with pure AE RU 58 668, which is known to impede nuclear translocation of the receptor [10].
• The recently described pure antiestrogen RU 58668 displayed potent antiproliferative activities in vitro on several ER+ human mammary cell lines, stimulated either by estradiol or by endogenous or exogenous growth factors [11].

Associations of RU 58 668 with other chemical compounds

• This process appeared reversible (i.e. ER accumulation due to OH-Tam rapidly vanished upon subsequent exposure to 17beta-estradiol (E2) or the pure antiestrogen RU 58668) [12].
• The effect of resveratrol on eNOS expression was not modified by the estrogen receptor antagonists ICI 182780 and RU 58668 [13].

Analytical, diagnostic and therapeutic context of RU 58 668

• Our results demonstrate that RU 58668 can reach the brain following a subcutaneous injection, but that it needs more time to reach the brain than it does to reach the pituitary [14].

References