印度阿比特龙

产品描述

Abiraterone (CB-7598) is an effective steroidal cytochrome P450 17alpha-hydroxylase-17,20-lyase (CYP17) inhibitor (IC50: 4 nM).

靶点活性

CYP17,2nM

体外活性

Abiraterone抑制体外增殖和雄激素受体调节的雄激素受体阳性前列腺癌细胞基因表达，这可能是通过抑制类固醇和抗雄激素受体实现的。更高浓度的Abiraterone抑制依普利酮激活的突变型雄激素受体。Abiraterone 取代WT-AR（EC50：13.4 μM）和T877A（EC50：7.9 μM）中的配体。Abiraterone醋酸盐明显抑制T分泌（48%），且可使LH浓度达到192%。Abiraterone抑制大鼠睾丸微粒的裂解酶活性（IC50：5.8 nM）。

体内活性

Abiraterone对睾丸激素水平的降低效果几乎切除睾丸的效果相同。Abiraterone对任何器官尺寸均无明显降低作用。Abiraterone可抑制人类睾丸微粒体中CYP17（IC50：72 nM）。与对照组相比，Abiraterone 降低 95%以上睾丸激素水平。

激酶实验

C17,20-lyase activity assay: Microsomes are diluted to a final protein concentration of 50 μg/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 °C for 10 minutes, the reaction is initiated by addition of βNADP to obtain a final concentration of 0.6 mM. Prior to the distribution of 600 μL of the reaction mixture in each tube, Abiraterone is evaporated to dryness under a stream of nitrogen and then are incubated at 37 °C for 10 minutes. After incubation with Abiraterone, 500 μL of the reaction mixture is transferred to tubes containing 1 μM of the enzyme substrate, 17OHP. After a further 10 minutes incubation, tubes are placed on ice and the reaction is stopped by addition of 0.1 ml NaOH 1N. Tubes are deep-frozen and stored at −20 °C until assayed for Δ4A levels. A Δ4A RIA is developed and automated on a microplate format using a specific antibody against Δ4A. The separation of free and bound antigen is achieved with a dextran-coated charcoal suspension. After centrifugation, aliquots of the clear supernatant are counted in duplicates in a 1450 MicrobetaPlus liquid scintillation counter. The Δ4A concentrations of unknown samples are determined from the standard curve. The detection limit is 0.5 ng/mL and the within and between assay coefficients of variation are 10.7 and 17.6%, respectively at an assay value of 13 ng/mL. The rate of enzymatic reaction is expressed as pmol of Δ4A formed per 10 minutes and per mg of protein. The value of maximum activity without inhibitor (control) is set at 100%. The IC50 values are calculated using non-linear analysis from the plot of enzyme activity (%) against log of inhibitor concentration.

细胞实验

LNCaP and VCaP cells are seeded in 96-well plates and grown in CSS-supplemented phenol red-free or FBS-supplemented media for 7 days. Cells are treated with Abiraterone at 24 hours and 96 hours after plating and cell viability is determined on day 7 by adding CellTiter Glo and measuring luminescence.(Only for Reference)

细胞系： LNCaP and VCaP cells

动物实验

动物模型：LAPC-4 xenograft mice

分子量

349.51

分子式

C24H31NO

CAS

154229-19-3

溶解度

Ethanol: 5.4 mg/mL (15.45 mM), Need ultrasonic

DMSO: 5 mg/mL (14.31 mM), Need ultrasonic

DMF: 8.75 mg/mL (25.04 mM), Need ultrasonic and warming

（ < 1 mg/ml refers to the product slightly soluble or insoluble )

储存条件

store at -80°C

备注

For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.