Abiraterone-CB-7598-DataSheet-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEAbirateroneCat. No.: HY-70013CAS No.: 154229-19-3Synonyms: CB-7598分式: CHNO分量: 349.51作靶點: Cytochrome P450作通路: Metabolic Enzyme/Protease儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMF : 8.75 mg/

2、mL (25.04 mM; Need ultrasonic and warming)Ethanol : 5.4 mg/mL (15.45 mM; Need ultrasonic)DMSO : 5 mg/mL (14.31 mM; Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 2.8611 mL 14.3057 mL 28.6115 mL5 mM 0.5722 mL 2.8611 mL 5.7223 mL10 mM 0.2861 mL 1.4306 mL 2.8611 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇

3、合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 Abiraterone種有效的不可逆的 CYP17A1 抑制劑，具有抗雄激素活性，抑制細胞素 p450 酶 CYP17 的17-羥化酶和 17,20-裂合酶活性，IC50 值 分別為 2.5 nM 和 15 nM.IC50 & Target IC50:17-hydroxylase (2.5 nM), 17,20-lyase (15 nM) 61/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE體外研究 Significant inhibition of

4、 proliferation of the AR-positive prostate cancer cell lines LNCaP and VCaP with dosesof Abiraterone 5 M is confirmed 2. Abiraterone shows IC50 values of 15 nM and 2.5 nM for the 17,20-lyase and 17-hydroxylase (CYP17 is a bifunctional enzyme with both 17-hydroxylase and 17,20-lyaseactivity). Abirate

5、rone inhibits human 17,20-lyase and 17-hydroxylase with IC50 of 27 and 30 nMrespectively 3. Abiraterone inhibits recombinant human 3HSD1 and 3HSD2 activity with competitive Kivalues of 2.1 and 8.8 M. 10 M Abiraterone is sufficient to completely block synthesis of 5-dione and DHTin both cell lines.Tr

6、eatment with abi significantly inhibited CRPC progression in the robustly growing subset,effectively putting a ceiling on tumor growth over 4 weeks of treatment (P3H-dehydroepiandrosterone(DHEA) depletion and 4-androstenedione (AD) accumulation are inhibited by Abiraterone in LNCaP, with anIC50 4.體內(nèi)

7、研究 The 0.5 mmol/kg/d Abiraterone treatment dose is previously shown to yield serum concentrations of about0.5 to 1 M. Xenograft tumor growth in the control group is widely variable, with some tumors growing slowlyand only a subset of tumors exhibiting robust growth 4. Following i.v. administration (

8、5 mg/kg) the clearance(Cl) and volume of distribution (Vd) are found to be 31.2 mL/min/kg and 1.97 L/kg, respectively. The AUC0-(area under the plasma concentration-time curve from time zero to infinity time point) is found to be 2675ng*h/mL. The terminal half-life (t1/2) is 0.73 h. Because of high

9、clearance, Abiraterone (ART) is quantifiableonly until 2 h following i.v. administration 5.PROTOCOLCell Assay 2 LNCaP and VCaP cells are seeded in 96-well plates and grown in CSS-supplemented phenol red-free orFBS-supplemented media for 7 days. Cells are treated with Abiraterone (5 M and 10 M) at 24

10、 and 96hours after plating and cell viability is determined on day 7 by adding CellTiter Glo and measuringluminescence 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 4Administration 45 Male NOD/SCID mice 6 to 8 weeks of age are surgically

11、 orchiectomized and implanted with a 5 mg 90-daysustained release DHEA pellet to mimic CRPC with human adrenal physiology. Two days later, 7106LAPC4 cells are injected subcutaneously with Matrigel. Tumor dimensions are measured 2 to 3 times perweek, and volume is calculated as lengthwidthheight0.52.

12、 Once tumors reach 300 mm3, mice arerandomly assigned to vehicle or Abiraterone treatment groups. Mice in the Abiraterone group are treated with5 mL/kg intraperitoneal injections of 0.5 mmol/kg/d (0.1 mL 5% benzyl alcohol and 95% safflower oil solution)and control mice with vehicle only, once daily

13、for 5 days per week over a duration of 4 weeks (n=8 mice pertreatment). Statistical significance between Abiraterone and vehicle treatment groups is assessed by ANOVAbased on a mixed-effect model.Rats 5Male Sprague-Dawley rats (n=8, 240-260 g) are used. Blood samples (450 L) are obtained following a

14、n i.v.5 mg/kg dose of ART into polypropylene tubes containing Na2-EDTA solution as an anticoagulant and at pre-dose, 0.12, 0.25, 0.5, 1, 2, 4, 6, 8 and 24 h (a sparse sampling protocol is adopted during blood collectionand at each time point blood is collected from four animals). Plasma is harvested

15、 by centrifuging the bloodusing a Biofuge at 1760g for 5 min and stored frozen at -8010C until analysis.2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEMCE 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 Nature. 2012 Jan 22;482(7383):116-9. Eur

16、 Urol. 2015 Aug;68(2):228-35. Anal Chem. 2016 Oct 4;88(19):9347-9350. Sci Rep. 2017 Mar 15;7:44409. Prostate. 2017 Dec;77(16):1550-1562.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Attard G, et al. Phase I clinical trial of a selective inhibitor of CYP17, abiraterone acetate

17、, confirms that castration-resistant prostatecancer commonly remains hormone driven. J Clin Oncol. 2008 Oct 1;26(28):4563-71.2. Richards J, et al. Interactions of abiraterone, eplerenone, and prednisolone with wild-type and mutant androgen receptor: a rationale forincreasing abiraterone exposure or

18、combining with MDV3100. Cancer Res. 2012 May 1;72(9):2176-82.3. Stein MN, et al. Androgen synthesis inhibitors in the treatment of castration-resistant prostate cancer. Asian J Androl. 2014 May-Jun;16(3):387-400.4. Li R, et al. Abiraterone inhibits 3-hydroxysteroid dehydrogenase: a rationale for increasing drug exposure in castration-resistantprostate