Fulvestrant(ZM 182780; ICI 182780 ) is a representative pure antiestrogen and a Selective Estrogen Receptor Down-regulator (SERD).

IC50 Value: 94 uM

Target: Estrogen Receptor

In contrast to the Selective Estrogen Receptor Modulators (SERMs) such as 4-hydroxytamoxifen that bind to estrogen receptor α (ERα) as antagonists or partial agonists, fulvestrant causes proteasomal degradation of ERα protein, shutting down the estrogen signaling to induce proliferation arrest and apoptosis of estrogen-dependent breast cancer cells.

in vitro: Fulvestrant competitively inhibits binding of oestradiol to the estrogen receptor. Fulvestrant blocks nuclear localization of the ER through impairing receptor dimerisation, and energy-dependent nucleo-cytoplasmic shuttling. Because of the instability of fulvestrant-ER complex, the binding of Fulvestrant with ER finally results in accelerated degradation of the ER protein  .Fulvestrant (10 nM) not only decreases IGF-IR mRNA levels but also decreases the half-life.Treatment with 100 μM Fulvestrant leads to a time dependent increase of TNFR1 and TRADD steady-state mRNA levels in MCF-7 cells. Fulvestrant is capable of down-regulating androgen receptor expression and diminishes androgenic responses in LNCaP human prostate cancer cells. Fulvestrant also significantly attenuates R1881-stimulated growth by 70%.

in vivo: Antitumor activity of ICI 182,780 was demonstrated with xenografts of MCF-7 and Br10 human breast cancers in nude mice. A single injection of ICI 182,780 provided antitumor efficacy equivalent to that of daily tamoxifen treatment for at least 4 weeks .

Clinical trial: A phase III trial comparing the efficacy and tolerability of Fulvestrant with Nolvadex in postmenopausal women with advanced breast cancer has been compeleted.