氟維司瓊作用機(jī)制 - Medchemexpress - MCE中國(guó)

1、Product Data SheetFulvestrantCat. No.: HY-13636CAS No.: 129453-61-8分式: CHFOS分量: 606.77作靶點(diǎn): Estrogen Receptor/ERR; Autophagy; Apoptosis作通路: Others; Autophagy; Apoptosis儲(chǔ)存式: 4C, protect from light* In solvent : -80C, 6 months; -20C, 1 month (protect from light)溶解性數(shù)據(jù)體外實(shí)驗(yàn) 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制備儲(chǔ)備液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請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲(chǔ)備液；旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存式和期限：-80C, 6 months; -20C, 1 m

3、onth (protect from light)。-80C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?6 個(gè)內(nèi)使，-20C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?1 個(gè)內(nèi)使。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍?。以下溶解案都?qǐng)先按照 In Vitro 式配制澄清的儲(chǔ)備液，再依次添加助溶劑：為保證實(shí)驗(yàn)結(jié)果的可靠性，澄 的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的式助溶1. 請(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubi

4、lity: 2.5 mg/mL (4.12 mM); Suspended solution; Need ultrasonic此案可獲得 2.5 mg/mL (4.12 mM) 的均勻懸濁液，懸濁液可于服和腹腔注射。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲(chǔ)備液加到 400 L PEG300 中，混合均勻；向上述體系中加50 L Tween-80，混合均勻；然后繼續(xù)加 450 L 理鹽定容 1 mL。2. 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)

5、; Suspended solution此案可獲得 2.5 mg/mL (4.12 mM，飽和度未知) 的均勻懸濁液，懸濁液可于服和腹腔注射。Page 1 of 2 www.MedChemE以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄均勻。DMSO 儲(chǔ)備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合3. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (4.12 mM); Clear solution此案可獲得 2.5 mg/mL (4.12 mM，飽和度未知) 的澄 溶液，此案不適于實(shí)驗(yàn)周 期在

6、半個(gè)以上的實(shí)驗(yàn)。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲(chǔ)備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Fulvestrant (ICI 182780) 種純抗雌激素，也 種有效的雌激素受體 (ER) 拮抗劑，IC50 為 9.4 nM。Fulvestrant 有 效抑制 ER 陽(yáng)性 MCF-7 細(xì)胞的長(zhǎng)，IC50 為 0.29 nM。Fulvestrant 還可誘導(dǎo)細(xì)胞噬 (autophagy) 和凋亡 (apoptosis)，并具有抗腫瘤功效。IC & Target IC50: 9.4 nM (Estrogen R

7、eceptor)1體外研究 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.體內(nèi)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.戶(hù)使本產(chǎn)品發(fā)表的科研獻(xiàn) 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