Fulvestrant是纯抗雌激素，也是一种雌激素受体拮抗剂，IC50为 9.4 nM。它抑制ER阳性 MCF-7 细胞的生长，IC50为 0.29 nM。它还是一种GPR30的激动剂。它可诱导细胞自噬和凋亡，有抗肿瘤作用。

Fulvestrant is a potent Estrogen Receptor antagonist (IC50: 9.4 nM).

The in vitro growth-inhibitory potency of Fulvestrant (ICI 182,780) exceeded that of ICI 164,384 in MCF-7 human breast cancer cells, where 50% inhibitory concentrations of 0.29 and 1.3 nM, respectively, were recorded [1]. The antiestrogen ICI 182780 (ICI) at 10 nM decreases Insulin-like growth factor I (IGF-I) receptor (IGF-IR) mRNA levels by 70% after treatment for 48 h [2]. ICI 182,780, in a concentration-dependent manner, significantly promoted neuron survival following exposure to either excitotoxic glutamate (200 muM)- or beta-amyloid(1-42) (1.5 muM)-induced neurodegeneration of hippocampal neurons [3].

When administered alone, parenterally (s.c.), to immature female rats ICI 182,780 was devoid of uterotropic activity and, when coadministered with estradiol, it effectively blocked the uterotropic action of estradiol in a dose-dependent manner [ED50 0.06 mg/kg/day s.c.]. Complete antagonism of estrogen action was achieved with a dose of 0.5 mg ICI 182,780/kg/day s.c [1]. Cylindrical epithelial cells slightly taller, epithelial dysplasia and an increase in smooth muscle layer were observed in the ventral prostate from ICI 182,780 ((10 mg/rat, s.c.)-treated rats. ICI 182,780 did not change the mRNA but decreased the protein levels for AR in the ventral prostate. The expression of ESR1 (mRNA and protein) was upregulated by ICI 182,780. ICI 182,780 decreased the phosphorylation state of ERK1/2, with no changes in total ERK1/2 levels. Ki-67-positive cells in the ventral prostate were also decreased by ICI 182,780 [4].

In brief, hippocampi were dissected from the brains of embryonic day 18 Sprague-Dawley rat fetuses, treated with 0.02% trypsin in Hanks' balanced salt solution (137 mM NaCl, 5.4 mM KCl, 0.4 mM KH2PO4, 0.34 mM Na2HPO4·7H2O, 10.0 mM glucose, and 10.0 mM HEPES) at 37°C for 5 min and dissociated by repeated passage through a series of fire-polished constricted Pasteur pipettes. For intracellular Ca2+ imaging analyses, approximately 10^4 cells were seeded onto poly-D-lysine (10 μg/ml)-coated 22-mm coverslips in covered 35-mm Petri dishes. For neuroprotection and Western immunoblotting analyses, approximately 10^6 cells/ml were seeded onto poly-D-lysine-coated solid black and clear bottom 96-well culture plates and 60-mm Petri dishes, respectively. Cells were grown in phenol-red free neurobasal medium supplemented with B27, 5 U/ml penicillin, 5 μg/ml streptomycin, 0.5 mM glutamine, and 25 μM glutamate at 37°C in 10% CO2 for the first 3 days and NBM without glutamate afterward. Cultures grown in serum-free NBM yields approximately 99.5% neurons and 0.5% glial cells [2].

MCF-7 cells were suspended in culture medium (no serum) and inoculated s.c. into the flank of adult female nude mice (0.1 ml/approximately 5 x 10^6 cells). Mice were maintained in a clean environment and were given sterile food and water. Estrogen supplementation was provided by ethynyl estradiol at 1 μg/ml in the water. Antiestrogen treatment was initiated when tumor diameter attained a minimum of 0.5 cm. The Br10 tumor at passage 49 was established by implantation of 1-2-mm^3 tumor fragments into the flank of anesthetized intact adult female nude mice. After 3 passages a reproducible pattern of growth was established without additional estrogen supplementation. Approximately two-thirds of animals established progressively growing tumors which attained measurable size (area, ≥70 mm2) after 6-7 weeks. Antiestrogen treatment was initiated at the time of transplantation. Tamoxifen was administered once daily p.o. at a dose of 10 mg/kg (1 ml/100 g body weight of aqueous dispersion in 0.5% Tween 80) and ICI 182,780 as a single s.c. injection of 5 mg/mouse (50 mg/ml in arachis oil). Tumor size was assessed weekly as the product of caliper measurements of the largest diameter and the axis perpendicular to it [1].

129453-61-8

C32H47F5O3S

606.77

ZM 182780;氟维司群;ICI 182780;ZD 9238

Ethanol:30.3 mg/mL (50 mM)
DMSO:60.7 mg/mL (100 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years