Abiraterone
(Synonyms: 阿比特龙,CB 7598,16-dien-3-ol,CB7598) 目录号 : GC17645A CYP17A1 inhibitor and an active metabolite of abiraterone acetate
Cas No.:154229-19-3
Sample solution is provided at 25 µL, 10mM.
Abiraterone (17-(3-pyridyl)androsta-5,16-dien-3β-ol) is a potent small-molecule inhibitor of CYP17 complex (17 alpha-monooxygenase) which is a member of the cytochrome P450 family consisting of 17 alpha-hydroxylase and C17,20-lyase and catalyzing the 17 alpha-hydroxylation of intermediates of steroid biosynthesis involved in testerone sysnthesis. Abiraterone inhibits CYP17 complex by binding to the haem iron of CYP17A1, which forms a 60o angle above the haem plane and packs against the central I helix with 3β-OH interacting with aspargine 202 in the F helix. Abiraterone is currently being investigated to treat late stage prostate cancer, in which it consistently suppresses testosterone levels, leads to significant reduction in PSA level, and prolong life in patients with castration-resistant prostate cancer (CRPC).
Reference
Natasha M. DeVore and Emily E. Scott. Structures of cytochrome P450 17A1 with prostate cancer drugs abiraterone and TOK-001. Nature 2012; 482: 116-120
Farshid Dayyani, Gary E. Gallick, Christopher J. Logothetis, Paul G. Corn. Novel therapies for metastatic castrate-resistant prostate cancer. JNCI J Natl Cancer Inst (2011); 103(22): 1665-1675
Kinase experiment [1]: | |
C17,20-lyase activity assay |
Microsomes were diluted to a final protein concentration of 50 g/ml in the reaction mixture which contained 0.25 M sucrose, 20 mM Tris–HCl (pH 7.4), 10 mM G6P and 1.2 IU/ml G6PDH. After equilibration at 37 ℃ for 10 min, the reaction was initiated by addition of NADP to obtain a final concentration of 0.6 mM. Prior to the distribution of 600 μl of the reaction mixture in each tube, test compounds were evaporated to dryness under a stream of nitrogen and then were incubated at 37 ℃ for 10 minutes. After incubation with Abiraterone, 500 μl of the reaction mixture was transferred to tubes containing 1M of the enzyme substrate, 17OHP. After a further 10 min incubation, tubes were placed on ice and the reaction was stopped by addition of 0.1 ml NaOH 1N. Tubes were deep-frozen and stored at -20℃ until assayed for Δ4A levels. A Δ4A RIA was developed and automated on a microplate format in our laboratory using a specific antibody against Δ4A. The separation of free and bound antigen was achieved with a dextran-coated charcoal suspension. After centrifugation, aliquots of the clear supernatant were counted in duplicates in a 1450 MicrobetaPlus liquid scintillation counter. The Δ4A concentrations of unknown samples were determined from the standard curve. The detection limit was 0.5 ng/ml and the within and between assay coefficients of variation were 10.7 and 17.6%, respectively at an assay value of 13 ng/ml. The rate of enzymatic reaction was expressed as pmol of Δ4A formed per 10 min and per mg of protein. The value of maximum activity without inhibitor (control) was set at 100%. The IC50 values were calculated using non-linear analysis from the plot of enzyme activity (%) against log of inhibitor concentration. |
Cell experiment [2]: | |
Cell lines |
LNCaP and VCaP cells |
Preparation method |
Limited solubility. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
Reaction Conditions |
24 h-96 h |
Applications |
Abiraterone is an inhibitor of CYP17A1 for the treatment of docetaxel-treated castration-resistant prostate cancer. Abiraterone inhibits in vitro proliferation and AR-regulated gene expression of AR-positive prostate cancer cells. |
Animal experiment [1]: | |
Animal models |
Adult male Wistar rats weighing 220–240 g |
Dosage form |
Administered by oral route at 10 ml/kg once daily for 3 days. |
Preparation method |
Distilled water with a few drops of Tween 80 |
Applications |
After 3 days of oral treatment at 50 mg/kg per day, abiraterone acetate markedly inhibits VP (-14%) and SV weights (-37%) without affecting adrenal weight (-7%). It also significantly inhibited T secretion (-48%) and in turn increased LH concentration (192%). |
Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
References: 1. Duc I, Bonnet P, Duranti V et al. In vitro and in vivo models for the evaluation of potent inhibitors of male rat 17alpha-hydroxylase/C17,20-lyase. J Steroid Biochem Mol Biol. 2003 Apr;84(5):537-42. 2. Richards J, Lim AC, Hay CW et al. Interactions of abiraterone, eplerenone, and prednisolone with wild-type and mutant androgen receptor: a rationale for increasing abiraterone exposure or combining with MDV3100. Cancer Res. 2012 May 1;72(9):2176-82. doi: 10.1158/0008-5472.CAN-11-3980. |
Cas No. | 154229-19-3 | SDF | |
别名 | 阿比特龙,CB 7598,16-dien-3-ol,CB7598 | ||
化学名 | (3S,8R,9S,10R,13S,14S)-10,13-dimethyl-17-pyridin-3-yl-2,3,4,7,8,9,11,12,14,15-decahydro-1H-cyclopenta[a]phenanthren-3-ol | ||
Canonical SMILES | CC12CCC(CC1=CCC3C2CCC4(C3CC=C4C5=CN=CC=C5)C)O | ||
分子式 | C24H31NO | 分子量 | 349.52 |
溶解度 | 15 mg/ml in DMF; 1 mg/ml in DMSO; 15 mg/ml in Ethanol | 储存条件 | Store at -20°C;Argon filled and protected from light |
General tips | 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;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效。 储备液的保存方式和期限:-80°C 储存时,请在 6 个月内使用,-20°C 储存时,请在 1 个月内使用。 为了提高溶解度,请将管子加热至37℃,然后在超声波浴中震荡一段时间。 |
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Shipping Condition | 评估样品解决方案:配备蓝冰进行发货。所有其他可用尺寸:配备RT,或根据请求配备蓝冰。 |
制备储备液 | |||
1 mg | 5 mg | 10 mg | |
1 mM | 2.8611 mL | 14.3053 mL | 28.6107 mL |
5 mM | 0.5722 mL | 2.8611 mL | 5.7221 mL |
10 mM | 0.2861 mL | 1.4305 mL | 2.8611 mL |
第一步:请输入基本实验信息(考虑到实验过程中的损耗,建议多配一只动物的药量) | ||||||||||
给药剂量 | mg/kg | 动物平均体重 | g | 每只动物给药体积 | ul | 动物数量 | 只 | |||
第二步:请输入动物体内配方组成(配方适用于不溶于水的药物;不同批次药物配方比例不同,请联系GLPBIO为您提供正确的澄清溶液配方) | ||||||||||
% DMSO % % Tween 80 % saline | ||||||||||
计算重置 |
计算结果:
工作液浓度: mg/ml;
DMSO母液配制方法: mg 药物溶于 μL DMSO溶液(母液浓度 mg/mL,
体内配方配制方法:取 μL DMSO母液,加入 μL PEG300,混匀澄清后加入μL Tween 80,混匀澄清后加入 μL saline,混匀澄清。
1. 首先保证母液是澄清的;
2.
一定要按照顺序依次将溶剂加入,进行下一步操作之前必须保证上一步操作得到的是澄清的溶液,可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet