Fulvestrant-ICI-182780-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEFulvestrantCat. No.: HY-13636CAS No.: 129453-61-8Synonyms: ICI 182780; ZD 9238; ZM 182780分式: CHFOS分量: 606.77作靶點(diǎn): Estrogen Receptor/ERR; Autophagy作通路: Others; Autophagy儲(chǔ)存式: 4C, protect from light* In solvent : -80C, 6 months; -20

2、C, 1 month (protect fromlight)溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 29 mg/mL (47.79 mM)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (4.12 mM); Suspended solution; Need ultrasonic2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (4.12 mM); Suspended solution1/4 Master of Small Molecul

3、es 您邊的抑制劑師www.MedChemE3. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (4.12 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Fulvestrant是有效的雌激素受體 (Estrogen Receptor) 拮抗劑，IC50值為 9.4 nM。IC50 & Target IC50: 9.4 nM (Estrogen Receptor) 1體外研究 Fulvestrant (ICI 182,780) is a potent and specific inhibitor

4、of estrogen action and demonstrates excellentgrowth-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. The relative binding affinities of Fulvestrant is 0.89compare with that of Estradiol. Fulvestr

5、ant has significantly increased antiestrogenic potency and retainspure estrogen antagonist activity 1. Fulvestrant is the first of a new type of endocrine treatment-anoestrogen receptor (ER) antagonist that downregulates the ER 2. Treatment of MCF-7 cells with 1 MTamoxifen has no effect on the expre

6、ssion of ER, whereas 100 nM Fulvestrant completely inhibits ERexpression 3.體內(nèi)研究 When administered alone, parenterally (s.c.), to immature female rats Fulvestrant (ICI 182,780) is devoid ofuterotropic activity and, when coadministered with Estradiol, it effectively blocks the uterotropic action ofEst

7、radiol in a dose-dependent manner (ED50: 0.06 mg/kg/day s.c.). Complete antagonism of Estrogen actionis achieved with a dose of 0.5 mg Fulvestrant/kg/day s.c. The effects of Fulvestrant administered p.o. arequalitatively similar but potency is reduced by an order of magnitude compare with s.c. dosin

8、g (ED50 0.46and complete antagonism at 5 mg/kg/day p.o.) 1. The antitumour activity of Fulvestrant is first demonstratedin two models of human breast cancer in nude mice. In one of these models, the growth of MCF-7 tumourxenografts, supported by continuous treatment with oestradiol, is completely bl

9、ocked for at least 4 weeksfollowing a single injection of Fulvestrant 5 mg. Similar reductions in growth are seen in the Br10 humantumour model. In other studies in nude mice bearing MCF-7 xenografts, Fulvestrant suppresses the growth ofestablished tumours for twice as long and tumour growth is dela

10、yed to a greater extent than is observed withTamoxifen treatment. Tamoxifen-resistant breast tumours, which grow in nude mice after long-term treatmentwith Tamoxifen, remain ensitive to growth inhibition by Fulvestrant 2. These are comparable to the tumorgrowth inhibition (TGI) observed for Tamoxife

11、n and Fulvestrant, which on day 40 are 86 and 88%,respectively 3.PROTOCOLCell Assay 3 MCF-7 or T47D cells are cultured in 10 cm dishes to 75% confluence in EMEM growth mediumsupplemented with 10% FBS and 10 g/mL human insulin. Twenty-four hours before treatment, the growthmedium is replaced with phe

12、nol red-free RPMI-1640 growth medium. A stock solution of 10 mM RAD1901 isprepared in DMSO. Dilutions of RAD1901 are prepared in RPMI growth medium (doses ranging from 10 to0.5 nM). Controls include 0.1% DMSO alone (vehicle), 1 nM Estradiol (E2), 100 nM Fulvestrant, and 1 MTamoxifen. Plated cells ar

13、e treated with RAD1901 or controls for 48 h, and then incubated for 15 min with2/4 Master of Small Molecules 您邊的抑制劑師www.MedChemEice-cold lysis buffer 1 mM EDTA, 0.5% Triton X-100, 5 mM NaF, 6 M urea, 1 mM sodium orthovanadate, 2.5mM sodium pyrophosphate, and 1 HALT protease inhibitor cocktail. Lysat

14、es are centrifuged at 2000g for 5min, and the supernatant is diluted 1 : 1 in lysis buffer. Ninety-six-well plates are coated overnight withcapture antibody (1 g/mL), washed three times in the manufacturers wash buffer, blocked with blockingbuffer for 2 h, and washed again. The prepared plates are i

15、ncubated with 100 L of the prepared cell lysatefor 2 h, washed, incubated with biotinylated detection antibody for 2 h, and washed again. After a 20 minincubation with streptavidin-horseradish peroxidase, the plates are washed and incubated with substratesolution for 20 min. The reaction is stopped

16、with stop solution, and the plates are analyzed on a microplatereader (OD450) 3.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Rats 1Administration 13 In studies with OVX rats, surgical preparation is performed at least 2 weeks before treatment

17、began. Tomeasure the duration of action of a single large dose of Fulvestrant, OVX rats are treated with a daily s.c.dose of 0.5 g of estradici benzoate beginning on the day of Fulvestrant administration and continued untilvaginal smears showed evidence of cornification. At that point the experiment

18、 is terminated and uterineweight is recorded. The arachis oil formulation used in these single dose duration of action studies contained50 mg Fulvestrant/mL.Mice 3Female athymic nude mice Crl:NU(NCr)-Foxn1nu are used for tumor xenograft studies. Fourteen days aftertumor cell implantation (designated

19、 as day 1 of the study), mice are 9 weeks of age, with body weightsranging from 21.4 to 32.5 g, individual tumor volumes ranging from 75 to 144 mm3, and a group mean tumorvolume (MTV) of 108 mm3. The mice are randomized into nine groups of 15 animals each and treated withvehicle, Tamoxifen (1 mg/ani

20、mal every other day), Fulvestrant (0.5 mg/animal daily), or RAD1901 (0.3, 1, 3,10, 30, 60, 90, and 120 mg/kg daily). Tumor volumes are evaluated twice per week. The tumor endpoint isdefined as an MTV of 1500 mm3 in the control group. Animals are also monitored for partial regression (PR)and complete

21、 regression responses.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) J Exp Clin Cancer Res. 2019 Aug 14;38(1):354. Br J Cancer. 2018 May 1:182-192. J Mol Med (Berl). 2019 Apr;97(4):541-552. Int J Biol Sci. 2019 Jan 1;15(3):522-532. Biomed Pharmacother. 2019 Jun 13;117:109092.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Wakeling AE