盐酸阿霉素_MSDS_作用_用途_盐酸阿霉素CAS号【25316-40-9】

Doxorubicin hydrochloride是一种有细胞毒性的蒽环类抗生素,用于治疗多种癌症。 Doxorubicin 在癌细胞中起作用的可能机制是嵌入 DNA 和破坏 topoisomerase-II 介导的DNA修复。

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阿霉素对机体可产生广泛的生物化学效应。具有强烈的细胞毒性作用。其作用机制主要是阿霉分子嵌入DNA而抑制核酸的合成。

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[ 描述 ]:

Doxorubicin hydrochloride是一种有细胞毒性的蒽环类抗生素,用于治疗多种癌症。 Doxorubicin 在癌细胞中起作用的可能机制是嵌入 DNA 和破坏 topoisomerase-II 介导的DNA修复。

[ 相关类别 ]:

信号通路 >> 抗体- 药物偶联物 >> ADC细胞毒素

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

天然产物 >> 其他

[ 靶点 ]

Topoisomerase II

[体外研究]

在最高测试浓度(分别为2μM和10μM)下阿霉素和辛伐他汀的组合可杀死97％的Hela细胞[2]。

[体内研究]

携带PC3异种移植物的小鼠注射2,4或8mg/kg多柔比星,并随时间测量肿瘤体积。 2mg/kg的剂量不影响肿瘤生长,而较高剂量最初延迟肿瘤生长(第18天和第22天p <0.05),4mg/kg或8mg/kg阿霉素显着降低PC3异种移植物中c-FLIP的水平。 [3]。单次腹膜内注射10mg/kg(多柔比星1)在大鼠中给药,每天10次腹膜内注射1mg/kg(多柔比星2),或每周5次腹膜内注射2mg/kg(多柔比星3)。在阿霉素1中第28天观察到80％的死亡率,而在第107天和第98天,阿霉素2和阿霉素3分别达到80％的死亡率。在多柔比星DOX1中,第2周的分数缩短减少30％,在阿霉素2中第13周减少55％,在阿霉素3中第13周减少42％[4]。

[细胞实验]

将160μLHela细胞悬浮液（3×10 4细胞/ mL）分配到三个96孔U形底微量培养板中，并在37℃，5％CO 2的完全湿润气氛中孵育24小时。在板1中，加入多柔比星（20μL;终浓度，0.1-2μM）和辛伐他汀（20μL;终浓度，0.25-2μM）的连续稀释液至终体积200μL并再孵育72小时。在板2和3中，加入每种药物（辛伐他汀或多柔比星，40μL）的连续稀释液。在24小时的温育期后，吸出培养基并在PBS中洗涤细胞。然后，加入其他药物（40μL）的连续稀释液并补充培养基至终体积为200μL，并孵育48小时。多柔比星和辛伐他汀单独用作阳性对照（每孔40μL），仅用溶剂处理的细胞被认为是阴性对照。为了评估细胞存活，向每个孔中加入20μLMTT溶液（PBS中5mg / mL）并孵育3小时。然后用150μLDMSO代替培养基，并通过重复移液溶液实现甲crystals晶体的完全溶解。然后通过ELISA板读数器在540nm测定吸光度。在4或8个孔中测定每种药物浓度并重复3次。阿霉素的细胞毒性/细胞抑制作用表示为相对存活率（％对照）并计算。阴性对照中细胞存活的百分比假定为100.相对存活率=（实验吸光度 - 背景吸光度）/（未处理对照的吸光度 - 背景吸光度）×100％[2]。

[动物实验]

小鼠[3]使用无胸腺雄性裸鼠（3-4周龄）。将PC3细胞（4×106）皮下注射到小鼠的侧腹中。将携带肿瘤的动物随机分配到治疗组（每组5或6只小鼠），并且当异种移植物达到约100mm 3的体积时开始治疗。使用数字卡尺测量肿瘤并使用以下公式计算体积：体积=宽度2×长度×0.52，其中宽度表示肿瘤的较短尺寸。如所示使用载体（含有0.1％BSA的PBS），阿霉素（2-8mg / kg），Apo2L / TRAIL（500μg/动物）或4mg / kg多柔比星的组合然后500μgApo2L/的施用来施用处理。落后。全身施用阿霉素，而在肿瘤内或全身施用Apo2L / TRAIL。所有治疗都给予一次。每天监测小鼠的不良反应迹象（无精打采和邋app的外观）。治疗似乎很好耐受。计算每个数据点的平均值±SEM。通过学生t检验分析治疗组之间的差异。当P <0.05时，差异被认为是显着的。大鼠[4]将30只雄性Sprague-Dawley大鼠（体重250-300g）随机分配到3个实验组中的1个：阿霉素方案1（多柔比星1，n = 10），阿霉素方案2（多柔比星2，n = 10），或阿霉素方案3（多柔比星3，n = 10）。对于所有阿霉素治疗方案，阿霉素的累积剂量为10mg / kg。附表1涉及以10mg / kg单次推注腹膜内注射阿霉素。附表2涉及以1mg / kg连续10天腹膜内注射多柔比星10次。附表3涉及5次腹膜内注射2mg / kg的阿霉素，每周一次，持续5周。在第一次阿霉素治疗之前和开始阿霉素治疗后每周一次，在所有存活的动物中评估血压和心脏功能，只要每组至少有3只大鼠。

[参考文献]

[1]. Nitiss JL, et al. Targeting DNA topoisomerase II in cancer chemotherapy.Nat Rev Cancer. 2009 May;9(5):338-50.

[2]. Sadeghi-Aliabadi H, et al. Cytotoxic evaluation of doxorubicin in combination with simvastatin against human cancer cells. Res Pharm Sci. 2010 Jul;5(2):127-33.

[3]. El-Zawahry A, et al. Doxorubicin increases the effectiveness of Apo2L/TRAIL for tumor growth inhibition of prostate cancerxenografts. BMC Cancer. 2005 Jan 7;5:2.

[4]. Hayward R, et al. Doxorubicin cardiotoxicity in the rat: an in vivo characterization. J Am Assoc Lab Anim Sci. 2007 Jul;46(4):20-32.

[相关活性小分子]

[ 沸点 ]:
810.3ºC at 760 mmHg

[ 熔点 ]:
216ºC

[ 分子式 ]:
C₂₇H₃₀ClNO₁₁

[ 分子量 ]:
579.980

[ 闪点 ]:
443.8ºC

[ 精确质量 ]:
579.150757

[ PSA ]:
206.07000

[ LogP ]:
1.50360

[ 外观性状 ]:
橙色-红色结晶固体

[ 蒸汽压 ]:
9.64E-28mmHg at 25°C

[ 储存条件 ]:
2-8°C

[ 水溶解性 ]:
H2O: 10 mg/mL, clear, red-orange

详细MSDS(安全技术说明书)

CHEMICAL IDENTIFICATION

RTECS NUMBER :: QI9295900

CHEMICAL NAME :: 5,12-Naphthacenedione, 10-((3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosy l)oxy)- 7,8,9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacety l)-1-methoxy-, hydrochloride, (8S-cis)-

CAS REGISTRY NUMBER :: 25316-40-9

LAST UPDATED :: 199709

DATA ITEMS CITED :: 59

MOLECULAR FORMULA :: C27-H29-N-O11.Cl-H

MOLECULAR WEIGHT :: 580.03

WISWESSER LINE NOTATION :: L E6 C666 BV MVT&&&J DQ HV1Q HQ KQ RO1 FO- FT6OTJ B1 CQ DZ &GH

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 2571 ug/kg/3W-I

TOXIC EFFECTS :: Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 12 mg/kg/26W-I

TOXIC EFFECTS :: Cardiac - cardiomyopathy including infarction Lungs, Thorax, or Respiration - acute pulmonary edema

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 16030 ug/kg

TOXIC EFFECTS :: Gastrointestinal - hypermotility, diarrhea Skin and Appendages - dermatitis, allergic (after topical exposure) Nutritional and Gross Metabolic - weight loss or decreased weight gain

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

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 21840 ug/kg

TOXIC EFFECTS :: Gastrointestinal - hypermotility, diarrhea Skin and Appendages - dermatitis, allergic (after topical exposure) Nutritional and Gross Metabolic - weight loss or decreased weight gain

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 12510 ug/kg

TOXIC EFFECTS :: Gastrointestinal - hypermotility, diarrhea Skin and Appendages - dermatitis, allergic (after topical exposure) Nutritional and Gross Metabolic - weight loss or decreased weight gain

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

ROUTE OF EXPOSURE :: Intramuscular

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 16 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 :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 698 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - lacrimation Behavioral - muscle weakness Gastrointestinal - hypermotility, diarrhea

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 11160 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 :: 7678 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 :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1245 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 :: Intramuscular

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 13700 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 :: Intravenous

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 5980 ug/kg

TOXIC EFFECTS :: Behavioral - food intake (animal) Behavioral - muscle weakness

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 60 mg/kg/30D-C

TOXIC EFFECTS :: Liver - changes in liver weight Endocrine - changes in spleen weight Blood - normocytic anemia

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 18900 ug/kg/21D-I

TOXIC EFFECTS :: Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 6300 ug/kg/3D-I

TOXIC EFFECTS :: Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 38 mg/kg/14W-I

TOXIC EFFECTS :: Cardiac - EKG changes not diagnostic of specified effects Kidney, Ureter, Bladder - other changes in urine composition Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 12480 ug/kg/13W-I

TOXIC EFFECTS :: Cardiac - changes in heart weight Blood - leukopenia Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - phosphatases

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 15 mg/kg/5W-I

TOXIC EFFECTS :: Cardiac - other changes Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 9 mg/kg/3W-I

TOXIC EFFECTS :: Cardiac - EKG changes not diagnostic of specified effects Nutritional and Gross Metabolic - weight loss or decreased weight gain Related to Chronic Data - death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 22400 ug/kg/4W-I

TOXIC EFFECTS :: Kidney, Ureter, Bladder - proteinuria Blood - normocytic anemia Blood - changes in leukocyte (WBC) count

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 12 mg/kg/6W-I

TOXIC EFFECTS :: Cardiac - other changes Related to Chronic Data - death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 40 mg/kg/7W-I

TOXIC EFFECTS :: Cardiac - other changes Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 15600 ug/kg/13W-I

TOXIC EFFECTS :: Blood - normocytic anemia Blood - leukopenia Biochemical - Metabolism (Intermediary) - other proteins

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 18 mg/kg/30D-C

TOXIC EFFECTS :: Endocrine - changes in thymus weight Blood - normocytic anemia Related to Chronic Data - death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Primate - monkey

DOSE/DURATION :: 27 mg/kg/2Y-I

TOXIC EFFECTS :: Tumorigenic - equivocal tumorigenic agent by RTECS criteria Blood - leukemia

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 6 mg/kg

SEX/DURATION :: male 2 week(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count) Reproductive - Paternal Effects - testes, epididymis, sperm duct Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland, accessory glands

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 4500 ug/kg

SEX/DURATION :: male 5 week(s) pre-mating

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

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 30 mg/kg

SEX/DURATION :: male 30 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - testes, epididymis, sperm duct

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 60 mg/kg

SEX/DURATION :: female 30 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Maternal Effects - ovaries, fallopian tubes

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

DOSE :: 18 mg/kg

SEX/DURATION :: male 30 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - testes, epididymis, sperm duct

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

DOSE :: 600 ug/kg

SEX/DURATION :: female 30 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Maternal Effects - ovaries, fallopian tubes

TYPE OF TEST :: Specific locus test

TYPE OF TEST :: Specific locus test

TYPE OF TEST :: DNA inhibition

TYPE OF TEST :: Mutation test systems - not otherwise specified

MUTATION DATA

TYPE OF TEST :: DNA inhibition

TEST SYSTEM :: Bird - chicken Embryo

DOSE/DURATION :: 900 nmol/L

REFERENCE :: JMCMAR Journal of Medicinal Chemistry. (American Chemical Soc., Distribution Office Dept. 223, POB POB 57136, West End Stn., Washington, DC 20037) V.6- 1963- Volume(issue)/page/year: 26,638,1983 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X3746 No. of Facilities: 275 (estimated) No. of Industries: 1 No. of Occupations: 8 No. of Employees: 7597 (estimated) No. of Female Employees: 4972 (estimated)

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[ 符号 ]:

GHS07, GHS08

[ 信号词 ]:
Danger

[ 危害声明 ]:
H302-H315-H319-H350

[ 警示性声明 ]:
P201-P305 + P351 + P338-P308 + P313

[ 个人防护装备 ]:
Eyeshields;full-face particle respirator type N100 (US);Gloves;respirator cartridge type N100 (US);type P1 (EN143) respirator filter;type P3 (EN 143) respirator cartridges

[ 危害码 (欧洲) ]:
T: Toxic;T+: Very toxic;

[ 风险声明 (欧洲) ]:
R45;R22

[ 安全声明 (欧洲) ]:
S53-S45-S36/37/39-S22-S7/9

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

[ WGK德国 ]:
3

[ RTECS号 ]:
QI9295900

[ 海关编码 ]:
2941909000

盐酸阿霉素上游产品

盐酸阿霉素下游产品

由松链丝菌浅灰色变株（Str.Peucetius var.Caesius）的培养液提取而得。本品化学结构与柔红霉素类似，因此可以由柔红霉素化学转化而制得。目前已可化学全合成。

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[ 海关编码 ]: 2932999099

[ 中文概述 ]:
2932999099. 其他仅含氧杂原子的杂环化合物. 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

[ Summary ]:
2932999099. other heterocyclic compounds with oxygen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

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