Fulvestrant是一种选择性雌激素受体降解剂（SERD），IC50为9.4 nM。同时，Fulvestrant 还是一种 GPR30 的激动剂，能有效抑制 ER 阳性 MCF-7 细胞的生长，IC50 为 0.29 nM。此外，Fulvestrant 还可诱导细胞自噬 (autophagy) 和凋亡 (apoptosis)，并具有抗肿瘤活性，可用于乳腺癌的相关研究。
别名：ICI 182780; ZD 9238; ZM 182780
Fulvestrant是一种选择性雌激素受体降解剂（SERD），IC50为0.094 nM。Fulvestrant 有效抑制ER阳性的MCF-7生长(IC50为 0.29 nM)，而对ER阴性的的 BT-20人类乳腺癌细胞的生长没有作用效果。Fulvestrant 使细胞在 G0/G1 期累积，也降低了能持续进行DNA合成的细胞比例。 Fulvestrant 竞争性地抑制雌二醇与雌激素受体结合。
EMBO Mol Med. 2023 Dec.
MYSM1 acts as a novel co-activator of ERα to confer antiestrogen resistance in breast cancer
JCI Insight. 2022 Sep 8;7(17):e151851.
Targeting ESR1 mutation-induced transcriptional addiction in breast cancer with BET inhibition
NPJ Breast Cancer. 2022 Jan;8(1):1.
Int J Biol Sci. 2018 Oct 3;14(12):1755-1768.
Inhibition of Estrogen Signaling Reduces the Incidence of BRCA1-associated Mammary Tumor Formation.
Oncotarget. 2016 Dec 20;7(51):83893-83906.
Breast Cancer Res Treat. 2015 Jan;149(1):69-79.
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数据来源 | Int J Biol Sci (2018 Oct). Figure 6. Fulvestrant (Abmole Bioscience, Houston, USA) |
| 方法 | subcutaneously | |
| 细胞系/动物模型 | Conditional Brca1-knockout and MMTV-Cre transgenic mice | |
| 浓度 | 250 mg/kg | |
| 处理时间 | - | |
| 实验结果 | The chemotherapeutic efficacy of fulvestrant was examined in 18 sets of allograft mice produced from tumors from 18 individuals. |
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数据来源 | Int J Biol Sci (2018 Oct). Figure 5. Fulvestrant (Abmole Bioscience, Houston, USA) |
| 方法 | subcutaneously | |
| 细胞系/动物模型 | Conditional Brca1-knockout and MMTV-Cre transgenic mice | |
| 浓度 | 250 mg/kg | |
| 处理时间 | - | |
| 实验结果 | In addition, histological analyses revealed that the number and size of lobular and ductal tubes were reduced in fulvestrant-treated mammary glands and their structure showed evidence of degeneration and shrinkage. |
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数据来源 | Int J Biol Sci (2018 Oct). Figure 4. Fulvestrant (Abmole Bioscience, Houston, USA) |
| 方法 | subcutaneously | |
| 细胞系/动物模型 | Conditional Brca1-knockout and MMTV-Cre transgenic mice | |
| 浓度 | 250 mg/kg | |
| 处理时间 | - | |
| 实验结果 | In addition, fulvestrant-treated tumors displayed large necrotic areas with a lower level of the proliferation marker, and higher levels of cleaved caspase-3 and positive TUNEL staining compared with untreated tumor tissues (Fig. 4C), suggesting that estrogen signaling contributes to altered aggressiveness of Brca1-mutant tumors. |
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数据来源 | Oncotarget (2016). Figure 5. ICI-182780 (Abmole Bioscience Kowloon, Hong Kong). |
| 方法 | ||
| 细胞系/动物模型 | CD4+CD62L+ T Cell | |
| 浓度 | 0.1 μM | |
| 处理时间 | 3 d | |
| 实验结果 | As shown in Figure 5A and 5B, neither MPP nor G15 showed noticeable effect on the decreased percentage of Th17 (IL-17A+CD4+ T) cells induced by arctigenin. Both ICI and PHTPP themselves did not affect the Th17 differentiation, but they markedly diminished the inhibitory effect of arctigenin. As expected, E2 could effectively decrease the percentage of Th17 cells. An addition of ICI also diminished the inhibitory effect of E2 on Th17 differentiation. Arctigenin markedly increased the expressions of ERβ target genes CAV1 and ENPP2, but showed no obvious effect on the expression of ERβ during Th17 differentiation (Figure 5C), which coincided well with the fact that arctigenin specifically promoted the expression of ERβ target genes in EL4 cells. |
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数据来源 | Breast Cancer Res Treat (2015). Figure 4.Fulvestrant was obtained either in the clinical formulation (Astrazeneca) or in the powder form (Abmole), |
| 方法 | tumor volume, Ki67 staining, western bolt | |
| 细胞系/动物模型 | T47D/FR | |
| 浓度 | 5 mg/week s.c. in 100 µL | |
| 处理时间 | 3 days(wb) or 8 weeks | |
| 实验结果 | "P7170 (in the context of a fulvestrant backbone) significantly decreased cell proliferation in T47D/FR tumors, but did not significantly increase apoptosis." |
-2.jpg) |
数据来源 | Breast Cancer Res Treat (2015). Figure 3.Fulvestrant was obtained either in the clinical formulation (Astrazeneca) or in the powder form (Abmole), |
| 方法 | tumor volume, western blot, H&E staining, Ki67 staining, TUNEL test | |
| 细胞系/动物模型 | MCF-7 | |
| 浓度 | 5 mg/week s.c. in 100 µL | |
| 处理时间 | 3 days(wb) or 4-6 weeks | |
| 实验结果 | The addition of 5 mg/kg/day P7170 to fulvestrant significantly decreased tumor volumes compared to fulvestrant alone after 3–4.5 weeks of treatment (p<0.05) |
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数据来源 | Breast Cancer Res Treat (2015). Figure 2.Fulvestrant was obtained either in the clinical formulation (Astrazeneca) or in the powder form (Abmole), |
| 方法 | flow cytometry | |
| 细胞系/动物模型 | MCF-7, MCF-7/FR, MCF-7/LTED, HCC-1428, T47D, T47D/FR | |
| 浓度 | 1 µM | |
| 处理时间 | 3-4 days | |
| 实验结果 | In MCF-7, MCF-7/LTED, T47D, and T47D/FR cells, the combination of P7170 and fulvestrant significantly increased apoptosis compared to either drug alone. |
| 体外实验* | |
|---|---|
| 细胞系 | MCF-7 |
| 方法 | MCF-7 cells were plated at 10 000 cells/well in 96-well culture plates in MEM with 10% fetal bovine serum, and they were allowed to adhere for 48 h. Thereafter, the cultures were washed with serum-free MEM and incubated in 100 μl serum-free MEM. After 72 h, the medium was removed and replaced with 2% charcoal-stripped FBS–MEM containing 10 pmol/l E2 with either RAD1901 or additional E2 at concentrations ranging from 10−15 to 10−6 mol/l. The medium was removed after 48 h of incubation and the cells were lysed by adding 100 μl of CellTiter Glo (Promega, Madison, Wisconsin, USA), diluted 1 : 1 in water, per well. The plates were gently mixed on a plate shaker for 10 min before the luminescent signal was measured on a luminometer. The EC50 and IC50 of the test compound were defined as the concentrations that resulted in half-maximum shift. |
| 浓度 | Ranging from 10−15 to 10−6 mol/l |
| 处理时间 | 48 h |
*上述方法来自公开文献，仅供相同目的实验参考。如实验目的、材料、方法不同，请参考其他文献。
| 体内实验* | |
|---|---|
| 动物模型 | MCF-7 xenograft models: Female athymic nude mice [Crl:NU(NCr)-Foxn1nu] |
| 配制 | Formulated for use as a homogenous suspension in 0.5% (w/v) methylcellulose in deionized water |
| 剂量 | 0.5 mg/animal daily |
| 给药处理 | subcutaneous injection |
*上述方法来自公开文献，仅供相同目的实验参考。如实验目的、材料、方法不同，请参考其他文献。
| 分子量 | 606.77 |
| 分子式 | C32H47F5O3S |
| CAS号 | 129453-61-8 |
| 溶解性（25°C） | DMSO 50 mg/mL |
| 储存条件 |
粉末型式 -20°C 3年；4°C 2年 溶于溶剂 -80°C 6个月；-20°C 1个月 |
| 运输方式 | 冰袋运输，根据产品的不同，可能会有相应调整。 |
*下述溶液配置方法仅为基于分子量计算出的理论值。不同产品在配置溶液前，需考虑其在不同溶剂中的溶解度限制。
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.6481 mL | 8.2404 mL | 16.4807 mL |
| 5 mM | 0.3296 mL | 1.6481 mL | 3.2961 mL |
| 10 mM | 0.1648 mL | 0.824 mL | 1.6481 mL |
| 小鼠 | 大鼠 | 兔 | 豚鼠 | 仓鼠 | 狗 | |
| 重量 (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| 体表面积 (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km 系数 | 3 | 6 | 12 | 8 | 5 | 20 |
| 动物 A (mg/kg) = 动物 B (mg/kg) × | 动物 B的Km系数 |
| 动物 A的Km系数 |
例如，依据体表面积折算法，将化合物用于小鼠的剂量20 mg/kg 换算成大鼠的剂量，需要将20 mg/kg 乘以小鼠的Km系数（3），再除以大鼠的Km系数（6），得到化合物用于大鼠的等效剂量为10 mg/kg。
[1] Johnston SJ, et al. Curr Med Chem. Fulvestrant - a novel endocrine therapy for breast cancer.
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Palazestrant是一种新型的，具有口服活性的，雌激素受体拮抗剂和选择性雌激素受体降解剂。可用于ER+/HER2+ 乳腺癌的相关研究。 |
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| Acolbifene
Acolbifene是一种 EM800 的活性代谢物，同时也是具有口服活性的纯抗雌激素和选择性的雌激素受体 (ER) 的拮抗剂，能抑制雌二醇诱导的 ERα (IC50 = 2 nM) 和 ERβ (IC50 = 0.4 nM) 转录活性，并具有抗癌活性。 |
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