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盐酸胺苯吖啶

盐酸胺苯吖啶用途

Amsacrine (mAMSA) 是肿瘤细胞 DNA 嵌入剂,还能抑制拓扑异构酶 II。

盐酸胺苯吖啶名称

[ CAS 号 ]:
54301-15-4

[ 中文名 ]:
胺苯吖啶

[ 英文名 ]:
acridinyl anisidide

[中文别名 ]:

安沙克林

[英文别名 ]:

Amsacrine (hydrochloride)

盐酸胺苯吖啶生物活性

[ 描述 ]:

Amsacrine (mAMSA) 是肿瘤细胞 DNA 嵌入剂,还能抑制拓扑异构酶 II。

[ 相关类别 ]:

信号通路 >> 自噬 >> 自噬

天然产物 >> 生物碱

研究领域 >> 癌症

[ 靶点 ]

Topoisomerase II

[体外研究]

Amsacrine以浓度依赖性方式阻断HEK 293细胞和非洲爪蟾卵母细胞中的HERG电流,IC50值分别为209.4 nM和2.0μM。 Amsacrine引起激活(-7.6 mV)和失活(-7.6 mV)的电压依赖性的负向变化。通过amsacrine的HERG当前阻滞不依赖于频率[1]。对不同浓度m-AMSA的正常人淋巴细胞的体外研究显示,染色体畸变水平增加,范围从8％到100％,并且增加SCE,范围是研究的最低浓度的正常值的1.5倍(0.005μg/ mL)至正常值的12倍(0.25μg/ mL)[3]。 Amsacrine诱导的U937细胞凋亡的特征是caspase-9和caspase-3活化,细胞内Ca2 +浓度增加,线粒体去极化和MCL1下调。 Amsacrine通过降低其稳定性诱导MCL1下调。此外,amsacrine处理的U937细胞显示AKT降解和Ca2 +介导的ERK失活[4]。

[体内研究]

在用不同剂量的安吖啶(0.5-12mg/kg)治疗的动物中,用9和12mg/kg治疗后,微核多色红细胞的频率显着增加。此外,本研究首次表明,amsacrine具有高致裂性发生率和低致气性发生率,而nocodazole在体内有丝分裂期具有高致气性和低致裂性发生率[2]。

[动物实验]

在三个分开的实验中研究了小鼠[2] Amsacrine。在第一个实验中，通过腹膜内注射0.5,1.5和4.5mg / kg的Amsacrine处理动物，并在处理后24小时取样骨髓。在此采样时间的初步负MN结果导致Amsacrine使用30小时的采样时间。因此，在第二个实验中，用0.5,1.5和4.5mg / kg的Amsacrine处理小鼠，并在处理后30小时取样骨髓。通过参考早期研究选择Amsacrine的剂量和取样时间，并且所选剂量在用于人化学疗法的剂量范围内。结果再次表明，小鼠骨髓中的微核率不受任何选定剂量的试验剂处理的影响，在30小时取样时间，因此，在第三个实验中，小鼠用6,9处理治疗后24和30小时取样12mg / kg的Amsacrine和骨髓。

[参考文献]

[1]. Thomas D, et al. Inhibition of cardiac HERG currents by the DNA topoisomerase II inhibitor amsacrine: mode of action. Br J Pharmacol. 2004 Jun;142(3):485-94.

[2]. Attia SM. Molecular cytogenetic evaluation of the mechanism of genotoxic potential of amsacrine and nocodazole in mouse bone marrow cells. J Appl Toxicol. 2013 Jun;33(6):426-33.

[3]. Kao-Shan CS, et al. Cytogenetic effects of amsacrine on human lymphocytes in vivo and in vitro. Cancer Treat Rep. 1984 Jul-Aug;68(7-8):989-97.

[4]. Lee YC, et al. Amsacrine-induced apoptosis of human leukemia U937 cells is mediated by the inhibition of AKT- and ERK-induced stabilization of MCL1. Apoptosis. 2017 Mar;22(3):406-420.

[相关活性小分子]

盐酸胺苯吖啶物理化学性质

[ 沸点 ]:
563ºC at 760 mmHg

[ 熔点 ]:
197-199ºC

[ 分子式 ]:
C₂₁H₂₀ClN₃O₃S

[ 分子量 ]:
429.92000

[ 闪点 ]:
294.3ºC

[ 精确质量 ]:
429.09100

[ PSA ]:
88.70000

[ LogP ]:
6.54050

[ 外观性状 ]:
固体;Light yellow to Amber to Dark green powder to crystal

[ 储存条件 ]:
库房通风低温干燥

盐酸胺苯吖啶MSDS

详细MSDS(安全技术说明书)

盐酸胺苯吖啶毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: PB1081000

CHEMICAL NAME :: Methanesulfon-m-anisidide, 4'-(9-acridinylamino)-, monohydrochloride

CAS REGISTRY NUMBER :: 54301-15-4

LAST UPDATED :: 198706

DATA ITEMS CITED :: 7

MOLECULAR FORMULA :: C21-H19-N3-O3-S.Cl-H

MOLECULAR WEIGHT :: 429.95

WISWESSER LINE NOTATION :: T C666 BNJ IMR BO1 DMSW1

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 181 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 20560 ug/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 110 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

MUTATION DATA

TYPE OF TEST :: Sister chromatid exchange

TEST SYSTEM :: Rodent - hamster Ovary

DOSE/DURATION :: 50 ug/L

REFERENCE :: JNCIAM Journal of the National Cancer Institute. (Washington, DC) V.1-60, 1940-78. For publisher information, see JJIND8. Volume(issue)/page/year: 60,1155,1978

盐酸胺苯吖啶安全信息

[ 符号 ]:

GHS06

[ 信号词 ]:
Danger

[ 危害声明 ]:
H301-H315-H319-H335

[ 警示性声明 ]:
P261-P301 + P310-P305 + P351 + P338

[ 个人防护装备 ]:
Eyeshields;Faceshields;Gloves;type P2 (EN 143) respirator cartridges

[ 危害码 (欧洲) ]:
T:Toxic;

[ 风险声明 (欧洲) ]:
R25;R36/37/38

[ 安全声明 (欧洲) ]:
S26-S45

[ 危险品运输编码 ]:
UN 2811

[ WGK德国 ]:
3.0

[ RTECS号 ]:
PB1081000

[ 包装等级 ]:
III

[ 危险类别 ]:
6.1(b)

[ 海关编码 ]:
2935009090

盐酸胺苯吖啶合成路线

详细合成路线

盐酸胺苯吖啶上下游产品

盐酸胺苯吖啶上游产品

盐酸胺苯吖啶下游产品

盐酸胺苯吖啶海关

[ 海关编码 ]: 2935009090

[ 中文概述 ]:
2935009090 其他磺（酰）胺. 增值税率:17.0% 退税率:9.0% 监管条件:无最惠国关税:6.5% 普通关税:35.0%

[ 申报要素 ]: 品名, 成分含量, 用途

[ Summary ]:
2935009090 other sulphonamides VAT:17.0% Tax rebate rate:9.0% Supervision conditions:none MFN tariff:6.5% General tariff:35.0%

盐酸胺苯吖啶文献

Aneuploidy induces profound changes in gene expression, proliferation and tumorigenicity of human pluripotent stem cells.

Nat. Commun. 5 , 4825, (2014)

Human pluripotent stem cells (hPSCs) tend to acquire genomic aberrations in culture, the most common of which is trisomy of chromosome 12. Here we dissect the cellular and molecular implications of th...

Induction of chromosomal aberrations (unstable and stable) by inhibitors of topoisomerase II, m-AMSA and VP16, using conventional Giemsa staining and chromosome painting techniques.

Mutagenesis 13 , 39-43, (1998)

Frequencies of symmetrical and asymmetrical exchange aberrations induced by two inhibitors of topoisomerase II, namely, 4'-(9-acridinylamino) methanesulfon-m-anisidide (m-AMSA) and etoposide (VP16), w...

Mechanism of antitumor drug action: poisoning of mammalian DNA topoisomerase II on DNA by 4'-(9-acridinylamino)-methanesulfon-m-anisidide.

Proc. Natl. Acad. Sci. U. S. A. 81 , 1361-1365, (1984)

The intercalative acridine derivative 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA), but not its isomer o-AMSA, is a potent antitumor drug that in mammalian cells stimulates the formation of...

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