4- OH-tamoxifen

Volume-sensitive chloride channels are also sensitive to triphenylethylene SERMs. Thus, tamoxifen, 4-OH-tamoxifen, and toremifene were all found to... 

The use of triphenylethylene SERMs as Pgp inhibitors for clinical application has been hampered by unacceptable toxicity at doses required to achieve adequate cellular concentration, which is likely due to the involvement of proteins with the ability to bind these compounds. For instance, toremifene is able to reverse MDR and to sensitize human renal cancer cells to vinblastine in vitro. However, in vivo toremifene is tightly bound to serum proteins, in particular a 1-acid glycoprotein (AAG), which may limit its tissue availability (Braybrooke et al. 2000). In agreement with this, Chatterjee and Harris (1990) have shown that tamoxifen and 4-OH-tamoxifen were similarly potent in reversing MDR in Chinese hamster ovary (CHO) cells with acquired resistance to adriamycin. However, the addition of AAG (0.5 to 2 mg/ml, the range found in vivo) to cell cultures decreased the effect of tamoxifen on reversing MDR, and at the highest AAG concentration there was a complete reversal of the effects of... 

SMC. These regulatory effects were abrogated by the use of estrogen receptor (ER) antagonists, tamoxifen (Tam), 4-OH-tamoxifen, or Raloxifen (Ral) (33). More recently, it was demonstrated using an antisense strategy that these effects of l7(3-estradiol on EC were mediated through ERa, whereas the effects on SMC were mediated via ER(3 (34). 

Lim YC et al (2006) Endoxifen, a secondary metabolite of tamoxifen, and 4-OH-tamoxifen induce similar changes in global gene expression patterns in MCF-7 breast cancer cells. J Pharmacol Exp Ther 318 503-512... 

SULT1A1 4-Nitrophenol Acetaminophen, Troglitazone, Minoxidil, 4-OH Tamoxifen, Apomorphone Adult Liver, Adult GI Tract, Adult Platelets, Placenta... 

Figure 5.12 Hydrogen-bond interactions between 4-OH-tamoxifen and ERa. Hydrogen-bond intermolecular interactions of 4-OH-tamoxifen cocomplexed with human ERa LBD usingtheX-raycrystallographicstructure3ERT at 1.9-A resolution [44] are shown. The conformation was visualized using 3D-Mol...

Chambon s group [40] was the first to address the issue of the target site estrogenlike spedfidty of 4-OH-tamoxifen using recombinant human ER. They reported... 

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