1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEApalutamideCat. No.: HY-16060CAS No.: 956104-40-8Synonyms: ARN-509分式: CHFNOS分量: 477.43作靶點(diǎn): Androgen Receptor作通路: Others儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 83.3 mg/mL (174.48 mM)

2、H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.24 mM); Suspended solution; Need ultrasonic and warming2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oil1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemESolubility: 2.5 mg/mL (5.24 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Apalutamide (ARN-509)是有效，競(jìng)爭(zhēng)

3、性的 雄激素受體 (AR) 拮抗劑，IC50 為 16 nM。IC50 & Target IC50: 16 nM (Androgen receptor) 1體外研究 Apalutamide (ARN-509) also exhibits low micromolar affinity (IC50 3 M) for the GABAA receptor inradioligand binding-assays and thus may potentially antagonize GABAA at therapeutic dose levels 1.Apalutamide is a potent

4、 androgen receptor (AR) antagonist that targets the AR ligand-binding domain andprevents AR nuclear translocation, DNA binding, and transcription of AR gene targets 2.體內(nèi)研究 Apalutamide (ARN-509) exhibits low systemic clearance, high oral bioavailability and long plasma half-life inboth mouse and dog,

5、 supporting once-daily oral dosing. Consistent with its long terminal-half-life,Apalutamide steady-state plasma-levels increases in repeat-dose studies, resulting in high C24hr levels andlow peak:trough ratios (ratio:2.5). Castrate male mice bearing LNCaP/AR xenograft tumors are treated witheither A

6、palutamide at doses of 1, 10 or 30 mg/kg/day. Thirteen of 20 Apalutamide (30 mg/kg/day)-treatedanimals exhibit 50% reduction in tumor-volume at day 28 versus 3 of 19 MDV3100 (30 mg/kg/day)-treatedmice 1.PROTOCOLCell Assay 1 Trypsinized VCaP cells are adjusted to a concentration of 100,000 cells per

7、mL in phenol-red-free RPMI1640 (with 5% CSS), and dispensed in 16 L aliquots into CellBIND 384 well plates. Cells are incubated for48 hours, after which ligand is added in a 16 L volume to the RPMI culture medium. For the antagonistmode assay, the ligands are diluted in culture medium also containin

8、g 30 pM R1881. After 7 daysincubation, 16 L of CellTiter-Glo Luminescent Cell Viability Assay is added and Relative LuminescenceUnits (RLUs) measured 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 1Administration 1 In vivo xenograft exper

9、iments to determine anti-tumor response are carried out in SHO SCID male mice.Mice are orchiectomized under isoflorane anesthesia and are given 2-3 days to recover prior to tumor cellinjection. LNCaP/AR(cs) cells are suspended in 50% RPMI, 50% Matrigel, and 5106 cells/xenograft areinjected in a volu

10、me of 100 L. Animals are observed weekly until tumor growth is apparent. From 24 d post-injection, tumors are measured weekly, and after 40-60 days post-injection, animals are randomized intocohorts of equivalent mean (150-250 mm3) and range tumor burden. All compounds (e.g., Apalutamide, 30mg/kg pe

11、r day) are administered daily by oral gavage. Statistical analyses are performed using GraphpadPrism.MCE has not independently confirmed the accuracy of these methods. They are for reference only.2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Mol Cancer Ther. 2016 Jul;15(7):1702-12. Mo

12、l Cancer Res. 2017 Jan;15(1):35-44.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Clegg NJ, et al. ARN-509: a novel antiandrogen for prostate cancer treatment. Cancer Res. 2012 Mar 15;72(6):1494-503.2. Smith MR, et al. Phase 2 Study of the Safety and Antitumor Activity of Apalutamide (ARN-509), a Potent Androgen Receptor Antagonist,in the High-risk Nonmetastatic Castration-resistant Prostate Cancer Cohort. Eur Urol. 2016 May 6. pii: S0302-2838(16)30133McePdfHeightC