阿扎胞苷_MSDS_用途_密度_阿扎胞苷CAS号【320-67-2】

5-Azacytidine是胞苷的核苷类似物,其通过捕获 DNA甲基转移酶特异性地抑制DNA甲基化。

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[ 描述 ]:

5-Azacytidine是胞苷的核苷类似物,其通过捕获 DNA甲基转移酶特异性地抑制DNA甲基化。

[ 相关类别 ]:

信号通路 >> 自噬 >> 自噬

信号通路 >> 表观遗传学 >> DNA甲基转移酶

信号通路 >> 细胞周期/DNA损伤 >> 核苷抗代谢药/类似物

研究领域 >> 癌症

[ 靶点 ]

DNMT1

Nucleoside Antimetabolite/Analog

Autophagy

[体外研究]

与多种基因相关的未甲基化CpG岛在肿瘤中部分或完全甲基化,并可被5-氮杂胞苷重新激活[1]。 5-氮杂胞苷在相同浓度范围内作为朋友红白血病细胞红细胞分化的弱诱导剂,它们影响DNA甲基转移酶活性[2]。 5-氮杂胞苷抑制L1210细胞,ID50和ID90值分别为0.019和约0.15μg/ mL [3]。

[体内研究]

当动物暴露于5-氮杂胞苷(100mg/kg,ip)2小时或更长时间时,TdR-3H掺入被显着抑制[3]。

[激酶实验]

通过将细胞悬浮于给定体积的0.05mol / LTris-HCl缓冲液（pH 7.4）中，并用Biosonik以70％最大输出进行声波提取30秒，从培养物中的LI 210细胞中分离粗无细胞提取物。在Model L Spinco超速离心机中以105,000×g离心60分钟（4℃）后收集上清液。无细胞提取物的最终蛋白质浓度约为3mg / mL。提取物用作酶的来源。测量核糖核苷酸还原酶活性。酶单位定义为以1moleole / hr的速率催化dCMP合成的量。用于测量嘧啶核苷（CR）和脱氧核苷（TdR，CdR）激酶的测定系统基本上是Chu和Fischer描述的那些。然而，通过在沸水浴中加热2分钟终止反应，并根据Bach的方法分离磷酸化衍生物。将50μl等分试样施加到1英寸的二乙氨基乙基纸盘上，然后将其置于计数小瓶中并用0.5mL 0.5mol / LPCA洗脱。 1小时后，加入12mL Diotol，测定放射性。

[细胞实验]

将20mL细胞（约1×10 4个细胞/ mL）用螺旋盖移液到灭菌的培养管中，并在37℃下孵育过夜。在加入1mL代谢物（或培养基）之前，通过加入1mL 5-氮杂胞苷（5-azaCR）或培养基一段给定的时间（从0到240分钟）开始实验。通过Model A Coulter计数器每天测定细胞生长两次，持续3天。为了测定IDSO和ID90值，将5mL L1210细胞（5×103细胞/ mL）与药物在37℃温育3天，并测定细胞生长。

[动物实验]

对于体内实验，用0.2mL给定浓度的5-氮杂胞苷（5-azaCR）腹膜内注射白血病小鼠（大约1×103细胞/动物）。 2小时后，通过注射0.5mL标记的代谢物（TdR-3H或UR-3H，10 /μCi/12.5μg）开始反应。 1小时后，通过颈椎骨折杀死动物（3只小鼠/组），用肝素处理腹水，收集，合并，然后立即在Sorvall冷冻离心机Model R2C-B中以800×g离心10分钟（ 4℃）。

[参考文献]

[1]. Christman JK. 5-Azacytidine and 5-aza-2'-deoxycytidine as inhibitors of DNA methylation: mechanistic studies and their implications for cancer therapy. Oncogene. 2002 Aug 12;21(35):5483-95.

[2]. Creusot F, et al. Inhibition of DNA methyltransferase and induction of Friend erythroleukemia cell differentiation by 5-azacytidineand 5-aza-2'-deoxycytidine. J Biol Chem. 1982 Feb 25;257(4):2041-8.

[3]. Li LH,et al. Cytotoxicity and mode of action of 5-azacytidine on L1210 leukemia. Cancer Res. 1970 Nov;30(11):2760-9.

[相关活性小分子]

[ 密度 ]:
2.1±0.1 g/cm3

[ 沸点 ]:
534.5±60.0 °C at 760 mmHg

[ 熔点 ]:
226-232 °C (dec.)(lit.)

[ 分子式 ]:
C₈H₁₂N₄O₅

[ 分子量 ]:
244.205

[ 闪点 ]:
277.0±32.9 °C

[ 精确质量 ]:
244.080765

[ PSA ]:
143.72000

[ LogP ]:
-1.99

[ 外观性状 ]:
白色结晶粉末

[ 蒸汽压 ]:
0.0±3.2 mmHg at 25°C

[ 折射率 ]:
1.823

[ 储存条件 ]:
通风低温干燥,与库房食品原料分开存放

[ 水溶解性 ]:
0.5-1.0 g/100 mL at 21 ºC

详细MSDS(安全技术说明书)

CHEMICAL IDENTIFICATION

RTECS NUMBER :: XZ3017500

CHEMICAL NAME :: 1,3,5-Triazin-2(1H)-one, 4-amino-1-beta-D-ribofuranosyl-

CAS REGISTRY NUMBER :: 320-67-2

LAST UPDATED :: 199801

DATA ITEMS CITED :: 87

MOLECULAR FORMULA :: C8-H12-N4-O5

MOLECULAR WEIGHT :: 244.24

WISWESSER LINE NOTATION :: T6NVN ENJ DZ A- BT5OTJ CQ DQ E1Q

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: Rinsed with water

ROUTE OF EXPOSURE :: Administration onto the skin

SPECIES OBSERVED :: Rodent - rabbit

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 6 mg/kg/10D-I

TOXIC EFFECTS :: Blood - leukopenia Blood - agranulocytosis

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 500 ug/kg

TOXIC EFFECTS :: Gastrointestinal - hypermotility, diarrhea Gastrointestinal - nausea or vomiting

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 572 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 :: 68 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 :: 229 mg/kg

TOXIC EFFECTS :: Behavioral - ataxia Gastrointestinal - hypermotility, diarrhea 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 :: Mammal - dog

DOSE/DURATION :: 7200 ug/kg

TOXIC EFFECTS :: Blood - other changes

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Bird - quail

DOSE/DURATION :: >100 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 :: Bird - wild bird species

DOSE/DURATION :: 100 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 :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 32500 ug/kg/5D-I

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - muscle contraction or spasticity Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Primate - monkey

DOSE/DURATION :: 30800 ug/kg/14D-I

TOXIC EFFECTS :: Blood - changes in bone marrow (not otherwise specified) Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases Related to Chronic Data - death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - hamster

DOSE/DURATION :: 180 mg/kg/9W-I

TOXIC EFFECTS :: Blood - leukopenia 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 :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 190 mg/kg/38W-I

TOXIC EFFECTS :: Tumorigenic - equivocal tumorigenic agent by RTECS criteria Lungs, Thorax, or Respiration - tumors Reproductive - Tumorigenic effects - testicular tumors

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 100 mg/kg/50W-I

TOXIC EFFECTS :: Tumorigenic - Carcinogenic by RTECS criteria Blood - lymphoma, including Hodgkin's disease Skin and Appendages - tumors

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Unreported

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1 mg/kg female 16 day(s) after conception

TOXIC EFFECTS :: Tumorigenic - Carcinogenic by RTECS criteria Reproductive - Tumorigenic effects - transplacental tumorigenesis Blood - lymphoma, including Hodgkin's disease

TYPE OF TEST :: TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 284 mg/kg/43W-I

TOXIC EFFECTS :: Tumorigenic - neoplastic by RTECS criteria Blood - lymphoma, including Hodgkin's disease

TYPE OF TEST :: TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 100 mg/kg/50W-I

TOXIC EFFECTS :: Tumorigenic - neoplastic by RTECS criteria Lungs, Thorax, or Respiration - tumors

TYPE OF TEST :: TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 90 mg/kg/8W-I

TOXIC EFFECTS :: Tumorigenic - neoplastic by RTECS criteria Lungs, Thorax, or Respiration - tumors

TYPE OF TEST :: TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1 mg/kg female 12 day(s) after conception

TOXIC EFFECTS :: Tumorigenic - Carcinogenic by RTECS criteria Blood - lymphoma, including Hodgkin's disease Reproductive - Tumorigenic effects - transplacental tumorigenesis

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 1 mg/kg

SEX/DURATION :: female 9 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 :: Intraperitoneal

DOSE :: 600 ug/kg

SEX/DURATION :: female 13 day(s) after conception

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

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 4 mg/kg

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

TOXIC EFFECTS :: Reproductive - Effects on Newborn - live birth index (measured after birth) Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain) Reproductive - Effects on Newborn - behavioral

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 450 ug/kg

SEX/DURATION :: female 13 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 :: 5 mg/kg

SEX/DURATION :: female 12 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Newborn - live birth index (measured after birth) Reproductive - Effects on Newborn - viability index (e.g., # alive at day 4 per # born alive)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 500 ug/kg

SEX/DURATION :: female 7 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 :: Intraperitoneal

DOSE :: 1 mg/kg

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

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - cytological changes (including somatic cell genetic material) Reproductive - Specific Developmental Abnormalities - Central Nervous System

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 2 mg/kg

SEX/DURATION :: female 10 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - Central Nervous System

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 2 mg/kg

SEX/DURATION :: female 11 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Specific Developmental Abnormalities - other developmental abnormalities

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Parenteral

DOSE :: 500 ug/kg

SEX/DURATION :: female 12 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain) Reproductive - Effects on Newborn - behavioral

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Parenteral

DOSE :: 100 ug/kg

SEX/DURATION :: female 12 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Newborn - physical

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Parenteral

DOSE :: 500 ug/kg

SEX/DURATION :: female 12 day(s) after conception

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

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Unreported

DOSE :: 500 ug/kg

SEX/DURATION :: female 12 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Unreported

DOSE :: 4 mg/kg

SEX/DURATION :: female 15 day(s) after conception

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

TYPE OF TEST :: Specific locus test

TYPE OF TEST :: Gene conversion and mitotic recombination

TYPE OF TEST :: Sex chromosome loss and nondisjunction

TYPE OF TEST :: Unscheduled DNA synthesis

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

TYPE OF TEST :: Micronucleus test

TYPE OF TEST :: Unscheduled DNA synthesis

TYPE OF TEST :: DNA inhibition

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

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

TYPE OF TEST :: Cytogenetic analysis

MUTATION DATA

TYPE OF TEST :: Cytogenetic analysis

TEST SYSTEM :: Mammal - species unspecified Lymphocyte

DOSE/DURATION :: 400 nmol/L

REFERENCE :: CGCGBR Cytogenetics and Cell Genetics. (S. Karger Pub., Inc., 79 Fifth Ave., New York, NY 10003) V.12- 1973- Volume(issue)/page/year: 41,71,1986 *** REVIEWS *** IARC Cancer Review:Animal Limited Evidence IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 26,37,1981 IARC Cancer Review:Animal Sufficient Evidence IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 50,47,1990 IARC Cancer Review:Human No Adequate Data IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 26,37,1981 IARC Cancer Review:Human No Adequate Data IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 50,47,1990 IARC Cancer Review:Group 2A IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 50,47,1990 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X5101 No. of Facilities: 88 (estimated) No. of Industries: 1 No. of Occupations: 3 No. of Employees: 1069 (estimated) No. of Female Employees: 698 (estimated)

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[ 符号 ]:

GHS07, GHS08

[ 信号词 ]:
Danger

[ 危害声明 ]:
H302-H350

[ 警示性声明 ]:
P201-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;R46;R22

[ 安全声明 (欧洲) ]:
S53-S22-S36/37/39-S45

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

[ WGK德国 ]:
3

[ RTECS号 ]:
XZ3017500

[ 海关编码 ]:
2934999090

详细合成路线

阿扎胞苷上游产品

阿扎胞苷下游产品

[ 海关编码 ]: 2934999090

[ 中文概述 ]:
2934999090. 其他杂环化合物. 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 ]:
2934999090. other heterocyclic compounds. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

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