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1、Product Data SheetEnzalutamideCat. No.: HY-70002CAS No.: 915087-33-1分式: CHFNOS分量: 464.44作靶点: Androgen Receptor; Autophagy作通路: Others; Autophagy储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 50 mg/mL (107.66 mM)H2O : 0.1 mg/mL (insoluble)* means soluble, but sa
2、turation unknown.SolventMass1 mg 5 mg 10 mgConcentration制备储备液1 mM 2.1531 mL 10.7657 mL 21.5313 mL5 mM 0.4306 mL 2.1531 mL 4.3063 mL10 mM 0.2153 mL 1.0766 mL 2.1531 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 month。-80C 储存时,请在 6 个内使,-20C 储存时,请在 1 个内使。体内实
3、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% salineSolubility: 2.5 mg/mL (5.38 mM); Clear solution此案可获得 2.5 mg/mL (5.38 mM
4、,饱和度未知) 的澄清溶液。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% corn oilSolubility: 2.5 mg/mL (5.38 mM); Clear solutionPage 1 of 2 www.MedChemE此案可获得 2.5 mg/mL (5.38 mM,饱和度未知) 的澄 溶液,此案不适于实验周 期在半个以上的实验。以 1 mL 作液为
5、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 Enzalutamide (MDV3100) 种雄激素受体 (androgen receptor (AR) 拮抗剂,在 LNCaP 前列腺细胞中抑制 AR 的 IC 50 值为 36 nM。Enzalutamide 种噬 (autophagy) 激活剂。IC & Target IC50: 36 nM (androgen-receptor, in LNCaP cells)1体外研究 Enzalutamide (MDV3100) has greater a
6、ffinity to AR than ICI 176334 does in a competition assay with 16-18Ffluoro-5-DHT (18-FDHT) in castration-resistant LNCaP/AR cells (AR-overexpressing). While Enzalutamide shows no agonismin LNCaP/AR prostate cells. Enzalutamide antagonizes induction of prostate-specific antigen (PSA) andtransmembran
7、e serine protease 2 (TMPRSS2), combination with the synthetic androgen R1881 in parental LNCaPcells. Enzalutamide inhibits the transcriptional activity of a mutant AR protein (W741C, mutation of Trp741 to Cys)1.Enzalutamide also prevents nuclear translocation and co-activator recruitment of the liga
8、nd-receptor complex2.体内研究 Enzalutamide (MDV3100) induces great tumor regression in castrate male mice bearing LNCaP/AR xenografts at adose of 10 mg/kg1.Enzalutamide shows dose-independent pharmacokinetics at intravenous and oral doses of 0.5-5 mg/kg4.PROTOCOLCell Assay 1 LNCaP cells (107 cells/condi
9、tion) are grown in RPMI media supplemented with 5% charcoalstripped serum for 22days, then treated with DMSO or 1 nM R1881, combined with an antiandrogen (DMSO, 1 M ICI 176334, 10 M ICI176334, 1 M RD162, 10 M RD162, 1 M MDV3100, or 10 M MDV3100) for 8 hours. An aliquot of cells areharvested for qRT-
10、PCR of PSA and TMPRSS2 mRNA. The remaining cells are cross-linked using 1% paraformaldehydefor 10 minutes, then glycine is added and samples centrifuged (4C, 4000 rpm, 5 minutes) to stop further crosslinking.Chromatin immunoprecipitation is performed using a chromatin immunoprecipitation assay kit.
11、ImmunoprecipitatedDNA is amplified by real-time PCR. Primers are PSA enhancer forward-ATGTTCACATTAGTACACCTTGCC and reverse-TCTCAGATCCAGGCTTGCTTACTGTC and TMPRSS2 enhancer forward-TGGTCCTGGATGATAAAAAAAGTTT and reverse-GACATACGCCCCACAACAGA1.MCE has not independently confirmed the accuracy of these met
12、hods. They are for reference only.Animal Mice3Administration 34 Following a 5-day acclimation period, 5- to 9-week-old male CB17SCID mice are castrated and allowed to recover foran additional 5 days before inoculation with tumor cells. LNCaP cells co-expressing exogenous AR and the AR-dependent repo
13、rter construct ARR2-Pb-Luc (LNCaP-AR-Lux cells) are used to generate a xenograft model of humanprostate cancer. Before implantation, LNCaP-AR-Lux cells are prepared by the addition of trypsin-EDTA, washed withcomplete medium, collected and resuspended at 20106 cells/mL. Cell suspensions are diluted
14、with Matrigel to 2106 cells/0.2 mL and delivered subcutaneously in the suprascapular region. Tumor growth is monitored to the volumeof 100 mm3 when treatment begins (80 days). The observed rate of tumor take with LNCaP-AR-Lux cells is between70% and 80%. Body weight and tumor volumes (width2length/2
15、) are measured two to three times per week with adigital caliper, and the average tumor volumes are determined. Test drugs are diluted in Tween 80:PEG 400, andstored at 4C until administration by oral gavage. Each group of mice (n=7) is treated daily for 28 consecutive dayswith 1, 10, or 50 mg/kg En
16、zalutamide, vehicle control, or 50 mg/kg ICI 176334. At the end of the treatment period orwhen tumor volume exceeded 1,000 mm3, animals are euthanized and blood and tissue samples are collected forPage 2 of 3 www.MedChemEanalysis.Rats4Male SD rats (n=3) are administered Enzalutamide through the tail
17、 vein (intravenous) and by oral gavage at 1 mg/kgand are kept in metabolic cages after dosing. Urine and feces samples are collected over the following time intervalsafter dosing: 0-2, 2-4, 4-6, 6-10, 10-24, 24-48, and 48-72 h. The metabolic cages are rinsed with distilled water, andresidues are add
18、ed to the urine samples at 72 h. To extract the Enzalutamide present in the feces, samples are shakenvigorously for 12 h with 50 % methanol.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 Discov. 2017 Jan;7(1):54-71. J Clin Invest. 20
19、20 Feb 3;130(2):699-714. Nat Commun. 2020 Apr 20;11(1):1884. Clin Cancer Res. 2017 Nov 15;23(22):6923-6933. Clin Cancer Res. 2015 Nov 1;21(21):4845-55.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Tran C, et al. Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science, 2009, 324 (5928), 787-790.2. Scher HI, et al. Antitumour activity of MDV3100 in cast
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