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安吖啶

安吖啶用途

Amsacrine 是肿瘤细胞 DNA 嵌入剂,还能抑制拓扑异构酶 II。

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安吖啶名称

[ CAS 号 ]:
51264-14-3

[ 中文名 ]:
安吖啶

[ 英文名 ]:
Amsacrine

[中文别名 ]:

[英文别名 ]:

m-AMSA
meta-Amsacrine
Amsacrine
4'-(Acridinylamino)methanesulfon-m-anisidide
Amsidyl
AMSA P-D
Amekrin
EINECS 257-094-3
AMSA, M-
Amsine

安吖啶生物活性

[ 描述 ]:

Amsacrine 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

信号通路 >> 细胞周期/DNA损伤 >> 拓扑异构酶

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]

在三个独立的实验中研究了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阴性MN结果导致使用30小时的采样时间用于安吖啶。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安吖啶的剂量和采样时间，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. 2016 Oct 19

[相关活性小分子]

安吖啶物理化学性质

[ 密度 ]:
1.4±0.1 g/cm3

[ 沸点 ]:
563.0±60.0 °C at 760 mmHg

[ 熔点 ]:
230-240ºC

[ 分子式 ]:
C₂₁H₁₉N₃O₃S

[ 分子量 ]:
393.459

[ 闪点 ]:
294.3±32.9 °C

[ 精确质量 ]:
393.114716

[ PSA ]:
88.70000

[ LogP ]:
2.12

[ 外观性状 ]:
白色固体

[ 蒸汽压 ]:
0.0±1.5 mmHg at 25°C

[ 折射率 ]:
1.723

[ 储存条件 ]:
库房通风低温干燥

安吖啶毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: PB1080000

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

CAS REGISTRY NUMBER :: 51264-14-3

BEILSTEIN REFERENCE NO. :: 0500176

LAST UPDATED :: 199801

DATA ITEMS CITED :: 58

MOLECULAR FORMULA :: C21-H19-N3-O3-S

MOLECULAR WEIGHT :: 393.49

WISWESSER LINE NOTATION :: T C666 BNJ IMR BO1 DMSW1

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 5405 ug/kg/3H-C

TOXIC EFFECTS :: Blood - changes in bone marrow (not otherwise specified)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Human

DOSE/DURATION :: 12 mg/kg

TOXIC EFFECTS :: Vascular - thrombosis distant from injection site Gastrointestinal - nausea or vomiting Blood - other changes

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 53420 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 :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 15470 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

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 33700 ug/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - dyspnea

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 50 mg/kg

TOXIC EFFECTS :: Behavioral - food intake (animal) Gastrointestinal - hypermotility, diarrhea Gastrointestinal - nausea or vomiting

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 6250 ug/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - dyspnea Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Primate - monkey

DOSE/DURATION :: 10400 ug/kg

TOXIC EFFECTS :: Blood - changes in bone marrow (not otherwise specified)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 546 mg/kg/13W-I

TOXIC EFFECTS :: Blood - changes in bone marrow (not otherwise specified) Related to Chronic Data - death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 90 mg/kg/24W-I

TOXIC EFFECTS :: Blood - changes in bone marrow (not otherwise specified) Nutritional and Gross Metabolic - weight loss or decreased weight gain Related to Chronic Data - changes in testicular weight

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 69250 ug/kg/5D-I

TOXIC EFFECTS :: Behavioral - muscle contraction or spasticity Blood - pigmented or nucleated red blood cells Related to Chronic Data - death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 125 mg/kg/5D-I

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Blood - changes in bone marrow (not otherwise specified) Related to Chronic Data - death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 1950 ug/kg/5D-I

TOXIC EFFECTS :: Blood - hemorrhage Blood - changes in bone marrow (not otherwise specified) Blood - changes in leukocyte (WBC) count

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Primate - monkey

DOSE/DURATION :: 13 mg/kg/5D-I

TOXIC EFFECTS :: Blood - changes in bone marrow (not otherwise specified) Blood - changes in leukocyte (WBC) count

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 30 mg/kg/24W-I

TOXIC EFFECTS :: Tumorigenic - Carcinogenic by RTECS criteria Gastrointestinal - tumors Skin and Appendages - tumors

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

DOSE :: 6486 ug/kg

SEX/DURATION :: male 3 week(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 8 mg/kg

SEX/DURATION :: female 6-9 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth) Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 15 mg/kg

SEX/DURATION :: male 1 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count)

TYPE OF TEST :: Micronucleus test

TYPE OF TEST :: DNA damage

TYPE OF TEST :: Cytogenetic analysis

MUTATION DATA

TYPE OF TEST :: DNA damage

TEST SYSTEM :: Mammal - species unspecified Lymphocyte

DOSE/DURATION :: 54 umol/L

REFERENCE :: CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut Sts., Philadelphia, PA 19106) V.1- 1941- Volume(issue)/page/year: 38,1300,1978 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X6337 No. of Facilities: 7 (estimated) No. of Industries: 1 No. of Occupations: 1 No. of Employees: 14 (estimated) No. of Female Employees: 14 (estimated)

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安吖啶安全信息

[ 危险品运输编码 ]:
UN 3249

[ 包装等级 ]:
III

[ 危险类别 ]:
6.1(b)

[ 海关编码 ]:
2935009090

安吖啶制备

邻甲氧基对硝基苯胺和酰氯反应，对氨基酰胺化进行保护，还原硝基为氨基，以甲磺酰氯对该氨基进行酰化使形成甲磺酰胺基，再选择性水解脱去1位氨基上的保护基，最后和9-氯吖啶反应，得到安吖啶。

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安吖啶海关

[ 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%

安吖啶

安吖啶用途

安吖啶名称

安吖啶生物活性

安吖啶物理化学性质

安吖啶毒性和生态

CHEMICAL IDENTIFICATION

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

MUTATION DATA

安吖啶安全信息

安吖啶制备

安吖啶海关

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