Fulvestrant (ICI 182780), a Pure Antiestrogen, is an Estrogen Receptor (ER) Antagonist
The estrogen receptor (ER) is expressed in the majority of breast tumors and in a number of endocrine tissues including the normal breast, uterus, and vagina, as well as in the pituitary and hypothalamus. Fulvestrant is the first of a new type of endocrine treatment——an oestrogen receptor (ER) antagonist that downregulates the ER and has no agonist effects. Fulvestrant has significantly increased antiestrogenic potency and retains pure estrogen antagonist activity. It is a pure antiestrogen and a potent estrogen receptor (ER) antagonist with an IC50 of 9.4 nM. Fulvestrant is also a GPR30 agonist. Fulvestrant effectively inhibits the growth of ER-positive MCF-7 cells with an IC50 of 0.29 nM. It also induces autophagy and has antitumor efficacy. In addition, Fulvestrant completely blocks the trophic actions of oestrogens without exerting any partial agonist effects. It reduces the expression of oestrogen receptor, progesterone receptor, and proliferative and cell turnover indices.
Fulvestrant (ICI 182780) is a pure antiestrogen and a potent ER antagonist.
The antiuterotrophic potency of Fulvestrant in the immature rat was more than 10-fold greater than that of ICI 164,384. Fulvestrant is a potent and specific inhibitor of estrogen action and demonstrates excellent growth-inhibitory effects in both cell and animal models of human breast cancer. Fulvestrant inhibits MCF-7 human breast cancer cells growth with the IC50 of 0.29 nM. The relative binding affinities of Fulvestrant is 0.89. It also has significantly increased antiestrogenic potency and retains pure estrogen antagonist activity.
In summary, Fulvestrant is a new type of endocrine treatment – an ER antagonist with a novel mode of action. Fulvestrant disrupts ER dimerisation and nuclear localisation, completely blocking ER-mediated transcriptional activity and accelerating receptor degradation. Consequently, fulvestrant also blocks the activity of oestrogen-regulated genes associated with breast tumour progression, invasion, metastasis and angiogenesis.
Osborne CK, et al. Br J Cancer. 2004;90 Suppl 1(Suppl 1):S2-S6.;Wakeling AE, et al. Cancer Res. 1991;51(15):3867-3873.