氟维司琼作用机制 - Medchemexpress - MCE中国

1、Product Data SheetFulvestrantCat. No.: HY-13636CAS No.: 129453-61-8分式: CHFOS分量: 606.77作靶点: Estrogen Receptor/ERR; Autophagy; Apoptosis作通路: Others; Autophagy; Apoptosis储存式: 4C, protect from light* In solvent : -80C, 6 months; -20C, 1 month (protect from light)溶解性数据体外实验 DMSO : 29 mg/mL (47.79 mM)H2O :

2、 0.1 mg/mL (insoluble)* means soluble, but saturation unknown.SolventMass1 mg 5 mg 10 mgConcentration制备储备液1 mM 1.6481 mL 8.2404 mL 16.4807 mL5 mM 0.3296 mL 1.6481 mL 3.2961 mL10 mM 0.1648 mL 0.8240 mL 1.6481 mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存式和期限：-80C, 6 months; -20C, 1 m

3、onth (protect from light)。-80C 储存时，请在 6 个内使，-20C 储存时，请在 1 个内使。体内实验请根据您的实验动物和给药式选择适当的溶解案。以下溶解案都请先按照 In Vitro 式配制澄清的储备液，再依次添加助溶剂：为保证实验结果的可靠性，澄 的储备液可以根据储存条件，适当保存；体内实验的作液，建议您现现配，当天使； 以下溶剂前显的百分 指该溶剂在您配制终溶液中的体积占；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的式助溶1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubi

4、lity: 2.5 mg/mL (4.12 mM); Suspended solution; Need ultrasonic此案可获得 2.5 mg/mL (4.12 mM) 的均匀悬浊液，悬浊液可于服和腹腔注射。以 1 mL 作液为例，取 100 L 25.0 mg/mL 的澄 DMSO 储备液加到 400 L PEG300 中，混合均匀；向上述体系中加50 L Tween-80，混合均匀；然后继续加 450 L 理盐定容 1 mL。2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (4.12 mM)

5、; Suspended solution此案可获得 2.5 mg/mL (4.12 mM，饱和度未知) 的均匀悬浊液，悬浊液可于服和腹腔注射。Page 1 of 2 www.MedChemE以 1 mL 作液为例，取 100 L 25.0 mg/mL 的澄均匀。DMSO 储备液加到 900 L 20% 的 SBE-CD 理盐溶液中，混合3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (4.12 mM); Clear solution此案可获得 2.5 mg/mL (4.12 mM，饱和度未知) 的澄 溶液，此案不适于实验周 期在

6、半个以上的实验。以 1 mL 作液为例，取 100 L 25.0 mg/mL 的澄 DMSO 储备液加到 900 L 油中，混合均匀。BIOLOGICAL ACTIVITY物活性 Fulvestrant (ICI 182780) 种纯抗雌激素，也 种有效的雌激素受体 (ER) 拮抗剂，IC50 为 9.4 nM。Fulvestrant 有 效抑制 ER 阳性 MCF-7 细胞的长，IC50 为 0.29 nM。Fulvestrant 还可诱导细胞噬 (autophagy) 和凋亡 (apoptosis)，并具有抗肿瘤功效。IC & Target IC50: 9.4 nM (Estrogen R

7、eceptor)1体外研究 Fulvestrant (ICI 182780; ZD 9238; ZM 182780) is a potent and specific inhibitor of estrogen action and demonstratesexcellent growth-inhibitory effects in both cell and animal models of human breast cancer. Fulvestrant inhibits MCF-7human breast cancer cells growth with IC50 of 290 nM.

8、The relative binding affinities of Fulvestrant is 0.89. Fulvestranthas significantly increased antiestrogenic potency and retains pure estrogen antagonist activity1. Fulvestrant is thefirst of a new type of endocrine treatment-an oestrogen receptor (ER) antagonist that downregulates the ER3.Treatmen

9、t of MCF-7 cells with 1 M ICI 47699 has no effect on the expression of ER, whereas 100 nM Fulvestrantcompletely inhibits ER expression4.体内研究 When administered alone, parenterally (s.c.), to immature female rats Fulvestrant (ICI 182,780) is devoid of uterotropicactivity. Complete antagonism of Estrog

10、en action is achieved with a dose of 0.5 mg Fulvestrant/kg/day s.c. The effectsof Fulvestrant administered p.o. are qualitatively similar but potency is reduced by an order of magnitude comparewith s.c. dosing (ED50 0.46 and complete antagonism at 5 mg/kg/day p.o.)1. The anti-tumor activity of Fulve

11、strant isfirst demonstrated in two models of human breast cancer in nude mice. In one of these models, the growth of MCF-7tumor xenografts is completely blocked for at least 4 weeks following a single injection of Fulvestrant 5 mg. Similarreductions in growth are seen in the Br10 human tumor model.

12、In other studies in nude mice bearing MCF-7xenografts, Fulvestrant suppresses the growth of established tumours for twice as long and tumor growth is delayedto a greater extent than is observed with ICI 47699 treatment. ICI 47699-resistant breast tumors, which grow in nudemice after long-term treatm

13、ent with ICI 47699, remain ensitive to growth inhibition by Fulvestrant3. These arecomparable to the tumor growth inhibition (TGI) observed for ICI 47699 and Fulvestrant, which on day 40 are 86 and88%, respectively4.PROTOCOLCell Assay 3 MCF-7 or T47D cells are cultured in 10 cm dishes to 75% conflue

14、nce in EMEM growth medium. Twenty-four hoursbefore treatment, the growth medium is replaced with phenol red-free RPMI-1640 growth medium. A stock solutionof 10 mM RAD1901 is prepared in DMSO. Dilutions of RAD1901 are prepared in RPMI growth medium (dosesranging from 10 to 0.5 nM). Controls include 0

15、.1% DMSO alone (vehicle), 100 nM Fulvestrant, and 1 M ICI 47699.Plated cells are treated with RAD1901 or controls for 48 h, and then incubated for 15 min with ice-cold lysis buffer 1mM EDTA, 0.5% Triton X-100, 5 mM NaF, 6 M urea, 1 mM sodium orthovanadate, 2.5 mM sodium pyrophosphate,and 1 HALT prot

16、ease inhibitor cocktail. Lysates are centrifuged at 2000g for 5 min, and the supernatant is diluted 1: 1 in lysis buffer. Ninety-six-well plates are coated overnight with capture antibody (1 g/mL), washed three times inthe manufacturers wash buffer, blocked with blocking buffer for 2 h, and washed a

17、gain. The prepared plates arePage 2 of 3 www.MedChemEincubated with 100 L of the prepared cell lysate for 2 h, washed, incubated with biotinylated detection antibody for2 h, and washed again. After a 20 min incubation with streptavidin-horseradish peroxidase, the plates are washed andincubated with

18、substrate solution for 20 min. The reaction is stopped with stop solution, and the plates are analyzedon a microplate reader (OD450)3.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Rats1Administration 13 In studies with OVX rats, surgical prepar

19、ation is performed at least 2 weeks before treatment began. To measure theduration of action of a single large dose of Fulvestrant, OVX rats are treated with a daily s.c. dose of 0.5 g ofestradici benzoate beginning on the day of Fulvestrant administration and continued until vaginal smears showedev

20、idence of cornification. At that point the experiment is terminated and uterine weight is recorded. The arachis oilformulation used in these single dose duration of action studies contained 50 mg Fulvestrant/mL.Mice3Female athymic nude mice Crl:NU(NCr)-Foxn1nu are used for tumor xenograft studies. F

21、ourteen days after tumorcell implantation (designated as day 1 of the study), mice are 9 weeks of age, with body weights ranging from 21.4 to32.5 g, individual tumor volumes ranging from 75 to 144 mm3, and a group mean tumor volume (MTV) of 108 mm3.The mice are randomized into nine groups of 15 anim

22、als each and treated with vehicle, ICI 47699 (1 mg/animal everyother day), Fulvestrant (0.5 mg/animal daily), or RAD1901 (0.3, 1, 3, 10, 30, 60, 90, and 120 mg/kg daily). Tumorvolumes are evaluated twice per week. The tumor endpoint is defined as an MTV of 1500 mm3 in the control group.Animals are a

23、lso monitored for partial regression (PR) and complete regression responses.MCE has not independently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 Cancer Cell. 2020 Mar 16;37(3):387-402.e7. Cell Rep. 2019 Dec. Cell Rep. 2019 Oct 22;29(4):889-903.e10. J Med Chem. 2019 Nov 14;62(21):9593-9599. J Exp Clin Cancer Res. 2019 Aug 14;38(1):354.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Wakeling AE, et al. A potent specific pure antiestrogen with clinical