Enzalutamide-MDV3100-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEEnzalutamideCat. No.: HY-70002CAS No.: 915087-33-1Synonyms: MDV3100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 :

2、 50 mg/mL (107.66 mM)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.38 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% corn oil1/3 Master of Small Molecules 您边的抑制剂师www.MedChemESolubility: 2.5 mg/mL (5.38 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Enzalutamide (MDV3100)种雄激素受体 (androgen

3、receptor (AR) 拮抗剂，在LNCaP前列腺细胞中抑制AR 的 IC50 值为36 nM。IC50 & Target IC50: 36 nM (androgen-receptor, in LNCaP cells) 1体外研究 Enzalutamide has greater affinity to AR than Bicalutamide does in a competition assay with 16-18Ffluoro-5-DHT (18-FDHT) in castration-resistant LNCaP/AR cells (AR-overexpressing). Wh

4、ile Enzalutamide showsno agonism in LNCaP/AR prostate cells. Enzalutamide antagonizes induction of prostate-specific antigen(PSA) and transmembrane serine protease 2 (TMPRSS2), combination with the synthetic androgen R1881 inparental LNCaP cells. Enzalutamide inhibits the transcriptional activity of

5、 a mutant AR protein (W741C,mutation of Trp741 to Cys) 1. Enzalutamide also prevents nuclear translocation and co-activator recruitmentof the ligand-receptor complex 2.体内研究 Enzalutamide induces great tumor regression in castrate male mice bearing LNCaP/AR xenografts at a doseof 10 mg/kg 1. Enzalutam

6、ide shows dose-independent pharmacokinetics at intravenous and oral doses of0.5-5 mg/kg 4.PROTOCOLCell Assay 1 LNCaP cells (107 cells/condition) are grown in RPMI media supplemented with 5% charcoalstripped serumfor 22 days, then treated with DMSO or 1 nM R1881, combined with an antiandrogen (DMSO,

7、1 MBicalutamide, 10 M Bicalutamide, 1 M RD162, 10 M RD162, 1 M MDV3100, or 10 M MDV3100) for 8hours. An aliquot of cells are harvested for qRT-PCR of PSA and TMPRSS2 mRNA. The remaining cells arecross-linked using 1% paraformaldehyde for 10 minutes, then glycine is added and samples centrifuged(4C,

8、4000 rpm, 5 minutes) to stop further crosslinking. Chromatin immunoprecipitation is performed using achromatin immunoprecipitation assay kit. Immunoprecipitated DNA is amplified by real-time PCR. Primersare PSA enhancer forward-ATGTTCACATTAGTACACCTTGCC and reverse-TCTCAGATCCAGGCTTGCTTACTGTC and TMPR

9、SS2 enhancer forward-TGGTCCTGGATGATAAAAAAAGTTT and reverse-GACATACGCCCCACAACAGA 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 3Administration 34 Following a 5-day acclimation period, 5- to 9-week-old male CB17SCID mice are castrated and

10、allowed torecover for an additional 5 days before inoculation with tumor cells. LNCaP cells co-expressing exogenousAR and the AR-dependent reporter construct ARR2-Pb-Luc (LNCaP-AR-Lux cells) are used to generate axenograft model of human prostate cancer. Before implantation, LNCaP-AR-Lux cells are p

11、repared by theaddition of trypsin-EDTA, washed with complete medium, collected and resuspended at 20106 cells/mL.Cell suspensions are diluted with Matrigel to 2106 cells/0.2 mL and delivered subcutaneously in the2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEsuprascapular region. Tumor growth is m

12、onitored to the volume of 100 mm3 when treatment begins (80days). The observed rate of tumor take with LNCaP-AR-Lux cells is between 70% and 80%. Body weight andtumor volumes (width2length/2) are measured two to three times per week with a digital caliper, and theaverage tumor volumes are determined

13、. Test drugs are diluted in Tween 80:PEG 400, and stored at 4C untiladministration by oral gavage. Each group of mice (n=7) is treated daily for 28 consecutive days with 1, 10,or 50 mg/kg Enzalutamide, vehicle control, or 50 mg/kg Bicalutamide. At the end of the treatment period orwhen tumor volume

14、exceeded 1,000 mm3, animals are euthanized and blood and tissue samples arecollected for analysis.Rats 4Male SD rats (n=3) are administered Enzalutamide through the tail vein (intravenous) and by oral gavage at 1mg/kg and are kept in metabolic cages after dosing. Urine and feces samples are collecte

15、d over the followingtime intervals after dosing: 0-2, 2-4, 4-6, 6-10, 10-24, 24-48, and 48-72 h. The metabolic cages are rinsedwith distilled water, and residues are added to the urine samples at 72 h. To extract the Enzalutamidepresent in the feces, samples are shaken vigorously for 12 h with 50 %

16、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. Clin Cancer Res. 2017 Nov 15;23(22):6923-6933. Clin Cancer Res. 2015 Nov 1;21(21):4845-55. Clin Cancer Res. 2015 Apr 1;21(7):1675-87. Clin Cancer Re

17、s. 2014 Dec 15;20(24):6367-78.See more customer validations on HYPERLINK / 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 castra

18、tion-resistant prostate cancer: a phase 1-2 study. Lancet, 2010, 375(9724),1437-1446.3. Guerrero J, et al. Enzalutamide, an androgen receptor signaling inhibitor, induces tumor regression in a mouse model of castration-resistant prostate cancer. Prostate. 2013 Sep;73(12):1291-305.4. Kim TH, et al. Pharmacokinetics of enzalutamide, an an