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乙酸阿比特龙酯

乙酸阿比特龙酯用途

Abiraterone acetate是口服,有效,选择性和不可逆的 CYP17 抑制剂。

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乙酸阿比特龙酯名称

[ CAS 号 ]:
154229-18-2

[ 中文名 ]:
乙酸阿比特龙酯

[ 英文名 ]:
Abiraterone Acetate

[中文别名 ]:

[英文别名 ]:

17-(3-pyridyl)-5,16-androstadien-3beta-acetate
Abiraterone acetate
Zytiga
Abiraterone (acetate)

乙酸阿比特龙酯生物活性

[ 描述 ]:

Abiraterone acetate是口服,有效,选择性和不可逆的 CYP17 抑制剂。

[ 相关类别 ]:

信号通路 >> 代谢酶/蛋白酶 >> 细胞色素P450

研究领域 >> 癌症

[ 靶点 ]

CYP17[1]

[体外研究]

阿比特龙(Abi)乙酸酯是抗癌剂阿比特龙的酯前药,对于17,20-裂解酶和17α-羟化酶显示IC 50值为15 nM和2.5 nM(CYP17是具有17α-羟化酶和17的双功能酶, 20-裂解酶活性)。阿比特龙抑制人17,20-裂解酶和17α-羟化酶,IC50分别为27和30 nM [1]。用阿齐拉酮≥5μM剂量显着抑制AR阳性前列腺癌细胞系LNCaP和VCaP的增殖[2]。阿比特龙抑制重组人3βHSD1和3βHSD2活性,竞争性Ki值为2.1和8.8μM。 10μM阿比特龙足以完全阻断两种细胞系中5α-二酮和DHT的合成。阿比特龙的治疗显着抑制稳健生长子集中的CRPC进展,有效地使治疗4周内肿瘤生长达到上限(P <0.00001) [3]。

[体内研究]

阿比特龙(Abi)乙酸盐可延长去势抵抗性前列腺癌(CRPC)的存活率。 LNCaP中阿比特龙抑制[3H] -脱氢表雄酮(DHEA)消耗和Δ4-雄烯二酮(AD)积累,IC50 <1μM。先前显示0.5mmol/kg/d阿比特龙治疗剂量产生约0.5至1μM的血清浓度。对照组的异种移植肿瘤生长变化很大,一些肿瘤生长缓慢,只有一部分肿瘤表现出强劲的生长[3]。

[细胞实验]

将LNCaP和VCaP细胞接种在96孔板中，并在补充CSS的无酚红或FBS补充的培养基中生长7天。在接种后24和96小时，用阿比特龙（5μM和10μM）处理细胞，并通过添加CellTiter Glo并测量发光在第7天测定细胞活力[2]。

[动物实验]

小鼠[3]通过手术切除睾丸切除6至8周龄的雄性NOD / SCID小鼠，并植入5mg 90天持续释放DHEA小丸以模拟具有人肾上腺生理学的CRPC。两天后，用Matrigel皮下注射7×106个LAPC4细胞。肿瘤尺寸每周测量2至3次，体积计算为长×宽×高×0.52。一旦肿瘤达到300mm 3，将小鼠随机分配到载体或阿比特龙治疗组。阿比特龙组小鼠用5 mL / kg腹腔注射0.5 mmol / kg / d（0.1 mL 5％苄醇和95％红花油溶液）和对照小鼠仅用载体治疗，每日一次，每周5天以上持续4周（每次治疗n = 8只小鼠）。基于混合效应模型，通过ANOVA评估阿比特龙和媒介物治疗组之间的统计学显着性。

[参考文献]

[1]. 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 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.

[3]. Li R, et al. Abiraterone inhibits 3β-hydroxysteroid dehydrogenase: a rationale for increasing drug exposure in castration-resistant prostate cancer. Clin Cancer 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.

[相关活性小分子]

乙酸阿比特龙酯物理化学性质

[ 密度 ]:
1.1±0.1 g/cm3

[ 沸点 ]:
506.7±50.0 °C at 760 mmHg

[ 熔点 ]:
127-130°C

[ 分子式 ]:
C₂₆H₃₃NO₂

[ 分子量 ]:
391.546

[ 闪点 ]:
260.2±30.1 °C

[ 精确质量 ]:
391.251129

[ PSA ]:
39.19000

[ LogP ]:
6.55

[ 外观性状 ]:
固体;White to Light yellow to Light orange powder to crystal

[ 蒸汽压 ]:
0.0±1.3 mmHg at 25°C

[ 折射率 ]:
1.584

[ 储存条件 ]:
-20°C Freezer

乙酸阿比特龙酯安全信息

[ 符号 ]:

GHS08

[ 信号词 ]:
Danger

[ 危害声明 ]:
H360-H372

[ 警示性声明 ]:
P201-P260-P280-P308 + P313

[ 靶器官 ]:
Endocrine system

[ 危害码 (欧洲) ]:
Xi

[ 危险品运输编码 ]:
NONH for all modes of transport

[ RTECS号 ]:
BV7992100

[ 海关编码 ]:
2933399090

乙酸阿比特龙酯上下游产品

乙酸阿比特龙酯上游产品

乙酸阿比特龙酯下游产品

乙酸阿比特龙酯海关

[ 海关编码 ]: 2933399090

[ 中文概述 ]:
2933399090. 其他结构含非稠合吡啶环的化合物. 增值税率:17.0%. 退税率:13.0%. 监管条件:无. 最惠国关税:6.5%. 普通关税:20.0%

[ 申报要素 ]: 品名, 成分含量, 用途, 乌洛托品请注明外观, 6－己内酰胺请注明外观, 签约日期

[ Summary ]:
2933399090. other compounds containing an unfused pyridine ring (whether or not hydrogenated) in the structure. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

乙酸阿比特龙酯文献

Phase I clinical trial of the CYP17 inhibitor abiraterone acetate demonstrating clinical activity in patients with castration-resistant prostate cancer who received prior ketoconazole therapy.

J. Clin. Oncol. 28(9) , 1481-8, (2010)

Abiraterone acetate is a prodrug of abiraterone, a selective inhibitor of CYP17, the enzyme catalyst for two essential steps in androgen biosynthesis. In castration-resistant prostate cancers (CRPCs),...

Significant and sustained antitumor activity in post-docetaxel, castration-resistant prostate cancer with the CYP17 inhibitor abiraterone acetate.

J. Clin. Oncol. 28(9) , 1489-95, (2010)

The principal objective of this trial was to evaluate the antitumor activity of abiraterone acetate, an oral, specific, irreversible inhibitor of CYP17 in docetaxel-treated patients with castration-re...

Phase II multicenter study of abiraterone acetate plus prednisone therapy in patients with docetaxel-treated castration-resistant prostate cancer.

J. Clin. Oncol. 28(9) , 1496-501, (2010)

Persistence of ligand-mediated androgen receptor signaling has been documented in castration-resistant prostate cancers (CRPCs). Abiraterone acetate (AA) is a potent and selective inhibitor of CYP17, ...

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