Fulvestrant

Fulvestrant (ICI 182780) 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. Fulvestrant also induces autophagy and has antitumor efficacy^[1]. IC50 & Target:IC50: 9.4 nM (Estrogen Receptor)^[1] In Vitro:Fulvestrant (ICI 182780; ZD 9238; ZM 182780) 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. Fulvestrant has significantly increased antiestrogenic potency and retains pure estrogen antagonist activity^[1]. Fulvestrant is the first of a new type of endocrine treatment-an oestrogen receptor (ER) antagonist that downregulates the ER^[3]. Treatment of MCF-7 cells with 1 μM ICI 47699 has no effect on the expression of ERα, whereas 100 nM Fulvestrant completely inhibits ERα expression^[4]. In Vivo:When administered alone, parenterally (s.c.), Fulvestrant (ICI 182,780) is devoid of uterotropic activity in immature female rats.
Fulvestrant (0.5 mg/kg/day s.c) shows complete antagonism of Estrogen action.
Fulvestrant by po administration (5 mg/kg/day p.o.) is qualitatively similar with s.c.^[1].
In other studies in nude mice bearing MCF-7 xenografts, Fulvestrant suppresses the growth of established tumours for twice as long and tumor growth is delayed to a greater extent than is observed with ICI 47699 treatment^[3].
Fulvestrant exhibits tumor growth inhibition (TGI) on day 40 of 88%^[4].