乙酸阿比特龙酯作用机制 - Medchemexpress - MCE中国

1、Product Data SheetAbiraterone acetateCat. No.: HY-75054CAS No.: 154229-18-2分式: CHNO分量: 391.55作靶点: Cytochrome P450作通路: Metabolic Enzyme/Protease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 : 10 mg/mL (25.54 mM; Need ultrasonic)SolventMass1 mg 5 mg 10 mgConcentr

2、ation制备储备液1 mM 2.5540 mL 12.7698 mL 25.5395 mL5 mM 0.5108 mL 2.5540 mL 5.1079 mL10 mM 0.2554 mL 1.2770 mL 2.5540 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

3、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: 1 mg/mL (2.55 mM); Clear solution此案可获得 1 mg/mL (2.55 mM，饱和度未知) 的澄清溶液。以 1 mL 作液为例，取 100 L 10.0 mg/mL 的澄 DMSO 储备

4、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% (20% SBE-CD in saline)Solubility: 1 mg/mL (2.55 mM); Clear solution此案可获得 1 mg/mL (2.55 mM，饱和度未知) 的澄清溶液。Page 1 of 2 www.MedChemE以 1 mL 作液为例，取 100 L 10.0 mg/mL 的澄均匀。DMSO 储备液加到 900 L 20% 的 SBE-CD 理盐溶液中，混合

5、3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 1 mg/mL (2.55 mM); Clear solution此案可获得 1 mg/mL (2.55 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 作液为例，取 100 L 10.0 mg/mL 的澄 DMSO 储备液加到 900 L 油中，混合均匀。BIOLOGICAL ACTIVITY物活性 Abiraterone acetate 种服、有效、选择性和不可逆的 CYP17A1 抑制剂，具有抗雄激素活性。Abirateroneacetate是Abirater

6、one (CB7598) 的前药形式。IC & Target CYP17A12体外研究 Abiraterone (Abi) acetate is an ester prodrug of the anticancer agent Abiraterone, which shows IC50 values of 15 nMand 2.5 nM for the 17,20-lyase and 17-hydroxylase (CYP17 is a bifunctional enzyme with both 17-hydroxylase and17,20-lyase activity). Abirater

7、one inhibits human 17,20-lyase and 17-hydroxylase with IC50 of 27 and 30 nMrespectively1. Significant inhibition of proliferation of the AR-positive prostate cancer cell lines LNCaP and VCaP withdoses of Abiraterone 5 M is confirmed2. Abiraterone inhibits recombinant human 3HSD1 and 3HSD2 activitywi

8、th competitive Ki values of 2.1 and 8.8 M. 10 M Abiraterone is sufficient to completely block synthesis of 5-dione and DHT in both cell lines.Treatment with Abiraterone significantly inhibited CRPC progression in the robustlygrowing subset, effectively putting a ceiling on tumor growth over 4 weeks

9、of treatment (P0.00001)3.体内研究 Abiraterone (Abi) acetate prolongs survival in castration-resistant prostate cancer (CRPC). 3H-dehydroepiandrosterone (DHEA) depletion and 4-androstenedione (AD) accumulation are inhibited by Abirateronein LNCaP, with an IC501 M. The 0.5 mmol/kg/d Abiraterone treatment

10、dose is previously shown to yield serumconcentrations of about 0.5 to 1 M. Xenograft tumor growth in the control group is widely variable, with sometumors growing slowly and only a subset of tumors exhibiting robust growth3.PROTOCOLCell Assay 2 LNCaP and VCaP cells are seeded in 96-well plates and g

11、rown in CSS-supplemented phenol red-free or FBS-supplemented media for 7 days. Cells are treated with Abiraterone (5 M and 10 M) at 24 and 96 hours after platingand cell viability is determined on day 7 by adding CellTiter Glo and measuring luminescence2.MCE has not independently confirmed the accur

12、acy of these methods. They are for reference only.Animal Mice3Administration 3 Male NOD/SCID mice 6 to 8 weeks of age are surgically orchiectomized and implanted with a 5 mg 90-day sustainedrelease DHEA pellet to mimic CRPC with human adrenal physiology. Two days later, 7106 LAPC4 cells are injected

13、subcutaneously with Matrigel. Tumor dimensions are measured 2 to 3 times per week, and volume is calculated aslengthwidthheight0.52. Once tumors reach 300 mm3, mice are randomly assigned to vehicle or Abirateronetreatment groups. Mice in the Abiraterone group are treated with 5 mL/kg intraperitoneal

14、 injections of 0.5mmol/kg/d (0.1 mL 5% benzyl alcohol and 95% safflower oil solution) and control mice with vehicle only, once dailyfor 5 days per week over a duration of 4 weeks (n=8 mice per treatment). Statistical significance between Abirateroneand vehicle treatment groups is assessed by ANOVA b

15、ased on a mixed-effect model.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Page 2 of 3 www.MedChemE户使本产品发表的科研献 JCI Insight. 2019 Sep 5;4(17). pii: 122688. Br J Cancer. 2017 Mar 28;116(7):937-943. Mol Cancer Ther. 2015 Jan;14(1):59-69. Psychology, Univ

16、ersity of British Columbia. 2017 Aug.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Stein MN, et al. Androgen synthesis inhibitors in the treatment of castration-resistant prostate cancer. Asian J Androl. 2014 May-Jun;16(3):387-400.2. Richards J, et al. Interactions

17、 of abiraterone, eplerenone, and prednisolone with wild-type and mutant androgen receptor: a rationale for increasingabiraterone exposure or combining with MDV3100. Cancer Res. 2012 May 1;72(9):2176-82.3. Li R, et al. Abiraterone inhibits 3-hydroxysteroid dehydrogenase: a rationale for increasing dr

18、ug exposure in castration-resistant prostate cancer. ClinCancer Res. 2012 Jul 1;18(13):3571-9.4. Lee GT, et al. Intracrine androgen biosynthesis in renal cell carcinoma. Br J Cancer. 2017 Mar 28;116(7):937-943.5. A ODonnell, et al. Hormonal impact of the 17-hydroxylase/C17,20-lyase inhibitor abiraterone acetate (CB7630) in patients with prostate cancer. B