The Sound of Evolution
Tamoxifen
他莫昔芬
Mechanism of action:
Tamoxifen 是一種選擇性雌激素受體調節劑（selective estrogen receptor modulator）。Tamoxifen 會與雌激素受體（estrogen receptor）ERα/ERβ 結合，阻止內源性雌二醇（estradiol）與受體結合。在乳癌細胞中，tamoxifen 與雌激素受體形成的複合體無法有效吸引輔助活化因子（coactivators），反而偏向吸引輔助抑制因子（corepressors），使雌激素依賴的基因轉錄被抑制，抑制乳癌細胞增殖、促進凋亡。
Reference(s):
1. Jordan VC et al. (1993). Fourteenth Gaddum Memorial Lecture. A current view of tamoxifen for the treatment and prevention of breast cancer. Br J Pharmacol.
2. Howell A et al. (2005). Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment for breast cancer. Lancet.
3. Crewe HK et al. (2002). Metabolism of tamoxifen by recombinant human cytochrome P450 enzymes: formation of the 4-hydroxy, 4'-hydroxy and N-desmethyl metabolites and isomerization of trans-4-hydroxytamoxifen. Drug Metab Dispos.