阿比特龙代谢物

中文名称:

阿比特龙代谢物

中文同义词:

阿比特龙代谢物

英文名称:

17-(3-pyridyl)androsta-5,16-dien-3-one

英文同义词:

17-(3-pyridyl)androsta-5,16-dien-3-one;7-(3-pyridyl)androsta-5,16-dien-3-one;17-(3-pyridinyl)-androsta-4,16-diene-3-one;D4-abiraterone (CB-7627);D4-abiraterone;Abiraterone 3-Oxo 4,5-Dihydro Impurity/(8R,9S,10R,13S,14S)-10,13-Dimethyl-17-(pyridin-3-yl)-1,7,8,9,10,11,12,13,14,15-decahydro-2H-cyclopenta[a]phenanthren-3(6H)-one;Abiraterone (D4A);Δ4-Abiraterone

CAS号:

154229-21-7

分子式:

C24H29NO

分子量:

347.49

EINECS号:

相关类别:

Mol文件:

154229-21-7.mol

沸点 

504.6±50.0 °C(Predicted)

密度 

1.14±0.1 g/cm3(Predicted)

储存条件 

2-8°C

形态

powder

酸度系数(pKa)

5.32±0.12(Predicted)

颜色

white to beige

生物活性

D4-abiraterone 是阿比特龙的主要代谢产物。D4-abiraterone 是 CYP17A1, 3β-羟基类固醇脱氢酶 (3 βHSD) 和类固醇-5α-还原酶 ( SRD5A ) 的抑制剂，也是雄激素受体的拮抗剂。

靶点

CYP17A1, 3βHSD, SRD5A, androgen receptor

体外研究

D4-abiraterone (D4A ) (10 mM) nearly completely blocks conversion from D4-androstenedione (AD) to 5α-androstanedione and other 5α-reduced androgens. The affinity of D4-abiraterone for mutant (expressed in LNCaP, half-maximum inhibitory concentration (IC 50 =5.3 nM)) and wild type (expressed in LAPC4, IC 50 =7.9 nM) androgen receptor (AR) is greater than that of abiraterone (Abi) (IC 50 =418 and >500 nM, respectively). Compare with Abi, D4-abiraterone clearly better suppresses PSA, TMPRSS2 and FKBP5 expression in LNCAP, LAPC4 and C4-2 cell lines. D4-abiraterone also inhibits AR target gene expression in a dose-dependent manner.

体内研究

D4-abiraterone (D4A) is tenfold more potent than abiraterone (Abi) in blocking conversion from dehydroepiandrosterone (DHEA) by 3β-hydroxysteroid dehydrogenase (3βHSD) to D4-androstenedione (AD) in LNCaP and VCaP xenografts. 0.1 μM D4-abiraterone is equivalent to 1 μM Abi for blocking AD accumulation at 48 h in both LNCaP and VCaP xenografts. Progression is significantly delayed in the D4-abiraterone group compare with the Abi acetate group (P=0.011). D4-abiraterone treatment increases progression-free survival compare with Abi acetate.