Merck, T5648-5G, Tamoxifen

Tamoxifen (TC), a selective estrogen receptor modulator (SERM), is used against breast cancer in both men and women. It also acts as a prophylactic agent against breast cancer in women. This protein kinase C inhibitor and anti-angiogenetic factor is a prodrug that is metabolized to active metabolites 4-hydroxytamoxifen (4-OHT) and endoxifen by cytochrome P450 isoforms CYP2D6 and CYP3A4. In breast cancer, the gene repressor activity of tamoxifen against ERBB2 is dependent upon PAX2. TC blocks estradiol-stimulated vascular endothelial growth factor (VEGF) production in breast tumor cells. Patients with estrogen receptor-positive tumors are more likely to benefit from tamoxifen. It exhibits both estrogenic agonist and antagonist effects by selectively binding to estrogen receptors in different parts of the body. This nonsteroidal triphenylethylene derivative suppresses tumor growth and has been reported to be a carcinogen and teratogen in animals. Additionally, TC may also protect bone from estrogen-deficiency bone loss, lower plasma cholesterol, and have been implicated in liver carcinogenesis in rats. Other actions of TC include the reduction of plasma levels of insulin-like growth factor, induction of cells surrounding cancer cells to secrete transforming growth factor β, and inhibition of membrane lipid peroxidation, likely by decreasing membrane fluidity.