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地西他滨

地西他滨用途

Decitabine 是一种胞嘧啶类似物，为 DNA methyltransferase 抑制剂。

地西他滨名称

[ CAS 号 ]:
2353-33-5

[ 中文名 ]:
5-氮杂-2'-脱氧胞嘧啶核苷

[ 英文名 ]:
Decitabine

[中文别名 ]:

[英文别名 ]:

MFCD00043011
5-AZA-CDR
DAC
5-AZA-DC
Decitabine
5-DEOXY-2'-AZACYTIDINE
EINECS 219-089-4
5-Aza-1-(2-deoxy-β-D-ribofuranosyl)cytosine
2'-deoxy-5-azacytidine
5-Aza-2'-deoxycytidine

地西他滨生物活性

[ 描述 ]:

Decitabine (NSC 127716) 是一种DNA甲基转移酶抑制剂,通常用于治疗骨髓增生异常综合征(MDS) 和急性髓性白血病 (AML)。

[ 相关类别 ]:

信号通路 >> 表观遗传学 >> DNA甲基转移酶

研究领域 >> 癌症

[ 靶点 ]

DNMT1

DNMT3A

DNMT3B

[体外研究]

地西他滨处理在接触地西他滨后96小时显着抑制SNU719,NCC24和KATOIII的细胞生长。地西他滨诱导EBVaGC中G2/M阻滞和凋亡,抑制侵袭能力,并上调EBVaGC的E-钙粘蛋白表达[1]。在MDS-L敏感细胞中进行DAC处理后,H4N末端尾部(H4K8acK12acK16ac)的三乙酰化降低[2]。地西他滨上调HeLa细胞中的DCTPP1和dUTPase表达[3]。

[体内研究]

地西他滨(1.0 mg/kg,po)与四氢尿苷(THU)联合使用会导致女性出现严重毒性,导致对地西他滨毒性的敏感性增加与地西他滨血浆水平相关[4]。

[激酶实验]

使用连续分光光度测定法测定DCTPP1的焦磷酸水解酶活性。在标准反应（1mL最终体积）中，将10-250μM核苷酸底物在反应缓冲液（20mM MgCl 2,100mM KCl，0.75mg / mL BSA和4mM DTT）中孵育，浓度范围为0.1-1。 μM的DCTTP1。所有反应均在25℃下进行。

[细胞实验]

通过细胞计数和MTS测定分析细胞活力。将SNU719，NCC24和KATOIII以5×10 4个细胞/ mL的密度接种，仅与补充有FBS的RPMI-1640一起培养24小时。温育24小时后，在存在或不存在地西他滨（DAC）的情况下处理细胞120小时。用于细胞计数的细胞用胰蛋白酶消化并在DAC处理后0,24,48,72,96和120小时计数。通过台盼蓝排除法确定活细胞。对于MTS测定，将细胞（SNU719和NCC24：1×10 4 /孔，KATOIII：1×10 3 /孔）接种到96孔培养皿上。接种后，在指定的时间段将MTS加入井中。温育1小时后，在490nm处测量吸光度。

[动物实验]

将小鼠分配至四个剂量组和媒介物对照组。在给予四氢尿嘧啶（THU）或其载体以10mL / kg的剂量体积后1小时±5分钟给动物服用地西他滨（DAC）或其载体。基于范围发现研究选择DAC剂量，其中小鼠耐受六个口服剂量（2x /周）的0.1,0.2和0.4mg / kg DAC以及固定剂量的167mg / kg THU。选择固定的THU剂量（500mg / m 2）和THU与DAC给药之间的最佳时间（60分钟）。将小鼠中每体表面积剂量的毫克转换成毫克每千克体重剂量估计基于小鼠的米氏常数（Km）值。简而言之，小鼠剂量（毫克/体表面积（500mg / m 2）除以Km为3，将剂量转换为毫克每千克体重（167mg / kg）。指南中小鼠的工作体重范围为11-34克;本研究中使用的小鼠体重范围为24-38克。

[参考文献]

[1]. Nakamura M, et al. Decitabine inhibits tumor cell proliferation and up-regulates E-cadherin expression in Epstein-Barr virus-associated gastric cancer. J Med Virol. 2016 Jul 19.

[2]. Zhang C, et al. Quantitative proteomic analysis of histone modifications in decitabine sensitive and resistant leukemia cell lines. Clin Proteomics. 2016 Jul 5;13:14.

[3]. Requena CE, et al. The nucleotidohydrolases DCTPP1 and dUTPase are involved in the cellular response to decitabine. Biochem J. 2016 Jun 20.

[4]. Terse P, et al. Subchronic oral toxicity study of decitabine in combination with tetrahydrouridine in CD-1 mice. Int J Toxicol. 2014 Mar-Apr;33(2):75-85.

[5]. Yu J, et al. DNA methyltransferase expression in triple-negative breast cancer predicts sensitivity to decitabine. J Clin Invest. 2018 Jun 1;128(6):2376-2388.

[相关活性小分子]

阿扎胞苷 | SGI-1027 | N-酞酰-L-色氨酸 | 泽布拉林 | 罗米鲁曲 | 桧木醇 | 谷维素 | DC_517 | DC-05 | 葡萄糖缀合的MGMT抑制剂

地西他滨物理化学性质

[ 密度 ]:
1.9±0.1 g/cm3

[ 沸点 ]:
485.8±55.0 °C at 760 mmHg

[ 熔点 ]:
~200 °C (dec.)

[ 分子式 ]:
C₈H₁₂N₄O₄

[ 分子量 ]:
228.205

[ 闪点 ]:
247.6±31.5 °C

[ 精确质量 ]:
228.085861

[ PSA ]:
123.49000

[ LogP ]:
-1.93

[ 外观性状 ]:
白色结晶粉末

[ 蒸汽压 ]:
0.0±2.8 mmHg at 25°C

[ 折射率 ]:
1.780

[ 储存条件 ]:
通风低温干燥,与库房食品原料分开存放

[ 稳定性 ]:
Stable. May be light or air sensitive. Incompatible with strong oxidizing agents.

[ 水溶解性 ]:
acetic acid/water (1:1): 50 mg/mL

地西他滨MSDS

详细MSDS(安全技术说明书)

地西他滨毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: XZ3012000

CHEMICAL NAME :: s-Triazin-2(1H)-one, 4-amino-1-(2-deoxy-beta-D-erythro-pentofuranosyl)-

CAS REGISTRY NUMBER :: 2353-33-5

LAST UPDATED :: 199709

DATA ITEMS CITED :: 16

MOLECULAR FORMULA :: C8-H12-N4-O4

MOLECULAR WEIGHT :: 228.24

WISWESSER LINE NOTATION :: T6NVN ENJ DZ A- ET5OTJ B1Q CQ

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 190 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 :: 22 mg/kg

TOXIC EFFECTS :: Blood - leukopenia Blood - thrombocytopenia Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 1 mg/kg

SEX/DURATION :: female 8-11 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 :: 300 ug/kg

SEX/DURATION :: female 10-11 day(s) after conception

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 :: 300 ug/kg

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

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

TYPE OF TEST :: DNA inhibition

TYPE OF TEST :: DNA inhibition

TYPE OF TEST :: DNA inhibition

MUTATION DATA

TYPE OF TEST :: Cytogenetic analysis

TEST SYSTEM :: Rodent - hamster Ovary

DOSE/DURATION :: 5 umol/L

REFERENCE :: EJCAEL European Journal of Cancer. (Pergamon Press, c/o Elsevier Science, 660 White Plains Rd., Tarrytown, NY 10591) V.26-28(2/3), 1990-92. For publisher information, see EJCTEA Volume(issue)/page/year: 28,362,1992

地西他滨安全信息

[ 符号 ]:

GHS07, GHS08

[ 信号词 ]:
Danger

[ 危害声明 ]:
H302-H315-H319-H335-H341-H360

[ 警示性声明 ]:
P201-P261-P281-P305 + P351 + P338-P308 + P313

[ 个人防护装备 ]:
dust mask type N95 (US);Eyeshields;Gloves

[ 危害码 (欧洲) ]:
Xi:Irritant

[ 风险声明 (欧洲) ]:
R22;R36/37/38

[ 安全声明 (欧洲) ]:
S26

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

[ WGK德国 ]:
3

[ RTECS号 ]:
XZ3012000

地西他滨合成路线

详细合成路线

地西他滨上下游产品

地西他滨上游产品

地西他滨下游产品

地西他滨文献

The high mobility group A2 protein epigenetically silences the Cdh1 gene during epithelial-to-mesenchymal transition.

Nucleic Acids Res. 43(1) , 162-78, (2015)

The loss of the tumour suppressor E-cadherin (Cdh1) is a key event during tumourigenesis and epithelial-mesenchymal transition (EMT). Transforming growth factor-β (TGFβ) triggers EMT by inducing the e...

Epigenetic variation in the Egfr gene generates quantitative variation in a complex trait in ants.

Nat. Commun. 6 , 6513, (2015)

Complex quantitative traits, like size and behaviour, are a pervasive feature of natural populations. Quantitative trait variation is the product of both genetic and environmental factors, yet little ...

Flow-dependent epigenetic DNA methylation regulates endothelial gene expression and atherosclerosis.

J. Clin. Invest. 124(7) , 3187-99, (2014)

In atherosclerosis, plaques preferentially develop in arterial regions of disturbed blood flow (d-flow), which alters endothelial gene expression and function. Here, we determined that d-flow regulate...

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