依托泊苷_MSDS_用途_密度_依托泊苷CAS号【33419-42-0】

Etoposide是用于治疗多种癌症的化疗药物。 Etoposide通过与拓扑异构酶II和DNA形成复合物来抑制DNA合成。

[ 描述 ]:

Etoposide是用于治疗多种癌症的化疗药物。 Etoposide通过与拓扑异构酶II和DNA形成复合物来抑制DNA合成。

[ 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]

依托泊苷通过在RIN-m5F细胞中通过JNK/ERK介导的GSK-3下游触发的线粒体依赖性信号传导途径诱导细胞凋亡,从而对胰腺β细胞产生细胞毒性[1]。依托泊苷和贝伐单抗显着消除了P1球形成能力,这是一种与该细胞亚群凋亡相关的作用[2]。

[体内研究]

静脉注射到免疫缺陷小鼠中的依托泊苷(50μM)和贝伐单抗治疗的缺氧细胞显示诱导肺集落的能力降低,这也显示具有更长的潜伏期[2]。含有异环磷酰胺和卡铂的依托泊苷(10 mg/kg /天,静脉注射)可降低注射肝母细胞瘤细胞的NMRI裸鼠的肿瘤体积[3]。

[激酶实验]

在不存在或存在Z-DEVD-FMK（20μM）的情况下，接种RIN-m5F细胞并用依托泊苷（10-50μM）处理。在处理结束时（24小时），将细胞裂解物在37℃下与10μMAc-DEVD-AMC（半胱天冬酶-3 / CPP32底物）一起温育1小时。通过分光荧光计测量裂解的基板的荧光，激发波长为380nm，发射波长为460nm。使用具有570nm吸收带的二辛可宁酸蛋白质测定试剂盒测定细胞裂解物样品的蛋白质水平，以使对照和依托泊苷处理组之间的细胞数标准化。

[细胞实验]

RIN-m5F细胞是大鼠胰腺β-细胞系，在37℃下在含有5％CO 2 -95％空气混合物的加湿室中培养，并保持在补充有10％胎牛血清（FBS）的RPIM 1640培养基中。抗生素（100 U / mL青霉素和100μg/ mL链霉素）。将RIN-m5F细胞接种（2×10 4个细胞/孔）于96孔板中，使其粘附并回收过夜。将细胞更换为新鲜培养基，然后在不存在或存在药理学抑制剂（氯化锂（LiCl）-50μM;SP600125-20μM;PD98059-20μM）的情况下与依托泊苷（1-100μM）孵育24小时。

[动物实验]

建立了裸鼠HB（NMHB）的体内模型。只有具有胚胎成分的HB细胞才能在该模型中成功移植和再生。随后将每个NMHB移植到50只小鼠中用于治疗组。当大多数肿瘤达到50-100mm 3的体积时开始治疗。根据肿瘤体积对小鼠进行分层，随机分配给每组10只动物。注射肿瘤的动物在两个区块中给予异环磷酰胺，顺铂，多柔比星，依托泊苷（10mg / kg /天，iv）和卡铂作为单一药剂。每组原始异种移植物的一组10只动物作为对照组。在开始治疗后，以5天的间隔记录肿瘤生长25-30天，并计算相对肿瘤体积。在处死动物前24小时，腹膜内注射溴脱氧尿苷（BrdU）用于半定量测定肿瘤细胞的增殖活性（50μgBrdU/ g体重）。

[参考文献]

[1]. Lee KI, et al. Etoposide induces pancreatic β-cells cytotoxicity via the JNK/ERK/GSK-3 signaling-mediated mitochondria-dependent apoptosis pathway. Toxicol In Vitro. 2016 Jul 26. pii: S0887-2333(16)30147-3.

[2]. Calvani M, det al. Etoposide-Bevacizumab a new strategy against human melanoma cells expressing stem-like traits. Oncotarget. 2016 Jun 9. doi: 10.18632/oncotarget.9939.

[3]. Fuchs, J., et al. Comparative activity of cisplatin, ifosfamide, doxorubicin, carboplatin, and etoposide in heterotransplanted hepatoblastoma. Cancer, 1998. 83(11): p. 2400-7.

[相关活性小分子]

[ 密度 ]:
1.6±0.1 g/cm3

[ 沸点 ]:
798.1±60.0 °C at 760 mmHg

[ 熔点 ]:
236-251ºC

[ 分子式 ]:
C₂₉H₃₂O₁₃

[ 分子量 ]:
588.557

[ 闪点 ]:
263.6±26.4 °C

[ 精确质量 ]:
588.184265

[ PSA ]:
160.83000

[ LogP ]:
0.30

[ 外观性状 ]:
固体;White to Almost white powder to crystal

[ 蒸汽压 ]:
0.0±3.0 mmHg at 25°C

[ 折射率 ]:
1.662

[ 储存条件 ]:
避免光

[ 水溶解性 ]:
水溶性：实际上不溶；易溶于：甲醇,氯仿；微溶：乙醇

详细MSDS(安全技术说明书)

CHEMICAL IDENTIFICATION

RTECS NUMBER :: KC0190000

CHEMICAL NAME :: Epipodophyllotoxin-beta-D-ethyliden-glucoside, 4'-demethyl-

CAS REGISTRY NUMBER :: 33419-42-0

LAST UPDATED :: 199806

DATA ITEMS CITED :: 90

MOLECULAR FORMULA :: C29-H32-O13

MOLECULAR WEIGHT :: 588.61

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human

DOSE/DURATION :: 16 mg/kg/5D-I

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

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 160 ug/kg/3M-C

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - other changes

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Human

DOSE/DURATION :: 2630 ug/kg/10D-I

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

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Human - child

DOSE/DURATION :: 183 mg/kg/2H-C

TOXIC EFFECTS :: Behavioral - ataxia

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 57 ug/kg/2M-C

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - other changes

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1784 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Gastrointestinal - hypermotility, diarrhea Nutritional and Gross Metabolic - body temperature decrease

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 39 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Gastrointestinal - hypermotility, diarrhea

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

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: >200 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 - rat

DOSE/DURATION :: 58 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 :: 215 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 :: 64 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Gastrointestinal - ulceration or bleeding from stomach Skin and Appendages - hair

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

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 143 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 :: 15070 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 :: Oral

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 147 mg/kg

TOXIC EFFECTS :: Gastrointestinal - hypermotility, diarrhea Skin and Appendages - hair 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 - rabbit

DOSE/DURATION :: 37 mg/kg

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

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1400 mg/kg/5W-C

TOXIC EFFECTS :: Endocrine - other changes Blood - normocytic anemia Related to Chronic Data - death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1820 mg/kg/26W-C

TOXIC EFFECTS :: Endocrine - other changes Blood - changes in spleen

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 56 mg/kg/5W-C

TOXIC EFFECTS :: Liver - other changes Endocrine - other changes Blood - normocytic anemia

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 182 mg/kg/26W-C

TOXIC EFFECTS :: Endocrine - other changes Blood - normocytic anemia Related to Chronic Data - death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 700 mg/kg/5W-C

TOXIC EFFECTS :: Endocrine - other changes Blood - normocytic anemia Related to Chronic Data - death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 1165 mg/kg/26W-C

TOXIC EFFECTS :: Endocrine - other changes Blood - normocytic anemia Related to Chronic Data - death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 70 mg/kg/5W-C

TOXIC EFFECTS :: Endocrine - other changes Blood - normocytic anemia Related to Chronic Data - death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 116 mg/kg/26W-C

TOXIC EFFECTS :: Endocrine - other changes Blood - normocytic anemia Skin and Appendages - dermatitis, other (after systemic exposure)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 312 mg/kg

SEX/DURATION :: female 17-21 day(s) after conception lactating female 21 day(s) post-birth

TOXIC EFFECTS :: Reproductive - Maternal Effects - ovaries, fallopian tubes Reproductive - Effects on Newborn - viability index (e.g., # alive at day 4 per # born alive) Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 14630 ug/kg

SEX/DURATION :: female 7-17 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Effects on Newborn - behavioral

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 132 mg/kg

SEX/DURATION :: female 7-17 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Effects on Embryo or Fetus - fetal death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 44 mg/kg

SEX/DURATION :: multigenerations

TOXIC EFFECTS :: 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 :: 14 mg/kg

SEX/DURATION :: male 5 week(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 :: 45 mg/kg

SEX/DURATION :: male 90 day(s) pre-mating

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

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Unreported

DOSE :: 1400 mg/kg

SEX/DURATION :: male 28 day(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 :: 2 mg/kg

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

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - eye/ear Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Effects on Embryo or Fetus - fetal death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 1 mg/kg

SEX/DURATION :: female 7 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 1 mg/kg

SEX/DURATION :: female 8 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - Central Nervous System

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 1500 ug/kg

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

TOXIC EFFECTS :: Reproductive - Maternal Effects - oogenesis Reproductive - Effects on Embryo or Fetus - cytological changes (including somatic cell genetic material)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 70 mg/kg

SEX/DURATION :: male 5 week(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 :: 29120 ug/kg

SEX/DURATION :: male 26 week(s) pre-mating

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

TYPE OF TEST :: Micronucleus test

TYPE OF TEST :: Unscheduled DNA synthesis

TYPE OF TEST :: DNA inhibition

TYPE OF TEST :: Micronucleus test

TYPE OF TEST :: Micronucleus test

TYPE OF TEST :: Micronucleus test

TYPE OF TEST :: DNA damage

TYPE OF TEST :: Cytogenetic analysis

TYPE OF TEST :: Sister chromatid exchange

MUTATION DATA

TYPE OF TEST :: DNA inhibition

TEST SYSTEM :: Mammal - species unspecified Ascites tumor

DOSE/DURATION :: 50 umol/L

REFERENCE :: PAACA3 Proceedings of the American Association for Cancer Research. (Waverly Press, 428 E. Preston St., Baltimore, MD 21202) V.1- 1954- Volume(issue)/page/year: 24,309,1983 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X3180 No. of Facilities: 68 (estimated) No. of Industries: 1 No. of Occupations: 4 No. of Employees: 9321 (estimated) No. of Female Employees: 8677 (estimated)

[ 符号 ]:

GHS07, GHS08

[ 信号词 ]:
Danger

[ 危害声明 ]:
H302-H350

[ 警示性声明 ]:
P201-P280-P301 + P312 + P330-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

[ 风险声明 (欧洲) ]:
R45;R22

[ 安全声明 (欧洲) ]:
S53-S45

[ 危险品运输编码 ]:
UN 3249

[ WGK德国 ]:
3

[ RTECS号 ]:
KC0190000

[ 包装等级 ]:
II

[ 危险类别 ]:
6.1(a)

[ 海关编码 ]:
2932999099

详细合成路线

依托泊苷上游产品

依托泊苷下游产品

[ 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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