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齐多夫定

齐多夫定用途

Zidovudine 是一种核苷逆转录酶抑制剂 (NRTI),广泛用于治疗 HIV感染。Zidovudine 增强 CRISPR/Cas9调节的编辑频率。

齐多夫定名称

[ CAS 号 ]:
30516-87-1

[ 中文名 ]:
齐多夫定

[ 英文名 ]:
Zidovudine

[中文别名 ]:

[英文别名 ]:

Retrovis
bwa509u
Azitidin
BW-A509U
1-(3-Azido-2,3-dideoxy-β-D-ribofuranosyl)thymine
Thymidine, 3'-azido-3'-deoxy-
ZVD
3'-azido-3'-droxythymidine
retrovir
Timazid

齐多夫定生物活性

[ 描述 ]:

Zidovudine 是一种核苷逆转录酶抑制剂 (NRTI),广泛用于治疗 HIV感染。Zidovudine 增强 CRISPR/Cas9调节的编辑频率。

[ 相关类别 ]:

信号通路 >> 细胞周期/DNA损伤 >> CRISPR/Cas9

信号通路 >> 抗感染 >> HIV

研究领域 >> 感染

[ 靶点 ]

HIV-1

CRISPR/Cas9

[体外研究]

齐多夫定抑制SVG,原代人胎儿星形胶质细胞(PFA),外周血单核细胞(PBMC)和单核细胞衍生的巨噬细胞(MDM),EC50分别为17,113,18和5nM。齐多夫定抑制SVG,PFA,PBMC和MDM,EC90分别为0.205μM,44.157μM,0.481μM和0.219μM[1]。通过CRISPR/Cas9进行基因组编辑已经成为一种有效且可靠的方法,可以对活细胞基因组进行精确,有针对性的改变。 CXCR4是人类免疫缺陷病毒1型(HIV-1)感染的共同受体,并且被认为是AIDS的重要治疗靶标。 CXCR4通过与包膜蛋白gp120结合而介导病毒进入人CD4 +细胞。 CRISPR/Cas9介导的基因组编辑有效破坏人CXCR4基因,导致人原代CD4 + T细胞的HIV-1抗性。 Cas9介导的CXCR4消融显示出高特异性和可忽略的脱靶效应,而不影响细胞分裂和增殖[2]。

[体内研究]

与PBS载体相比,腹膜内注射NRTI拉米夫定(3TC),齐多夫定(AZT)或阿巴卡韦(ABC)抑制野生型小鼠中的激光诱导的脉络膜新血管形成(CNV)。在激光损伤后第3天达到峰值的RPE /脉络膜中VEGF-A的平均水平在3TC,AZT和ABC治疗的眼睛中与野生型小鼠中的对照眼相比显着降低,但在P2rx7-中没有显着降低。/-老鼠[3]。

[细胞实验]

在滴定浓度的ARV存在下，在所有细胞类型中进行测定。将5,000个SVG，2,500个PFA，200,000个PBMC或50,000个MDM细胞/孔接种到96孔板的一式三份孔中。二十四小时后，除去培养基并用含有ARV或DMSO（0.5％vol / vol）的培养基替换，并向细胞中加入等同的TCID50感染单位的荧光素酶报告病毒。在37℃温育16小时后，除去初始病毒接种物并用含有相同抗逆转录病毒药物（ARV）或DMSO（0.5％体积/体积）浓度的培养基替换。在感染后72小时，吸出培养基，裂解细胞并使用荧光素酶测定系统测量HIV-1感染。使用FLUOStar Optima酶标仪测量发光。使用GraphPad Prism软件[1]通过非线性回归分析确定抑制曲线和50％（EC50）和90％（EC90）有效浓度。

[动物实验]

使用小鼠[3] C57BL / 6J（野生型）和P2rx7 - / - 小鼠。使用Nlrp3 - / - 小鼠。将NRTI 3TC，AZT和ABC或P2X7拮抗剂A438079盐酸盐溶解在PBS中。对于CNV，每组小鼠注射一次1μLNRTIs（3TC，125 ng /μL; ABC，183 ng /μL; AZT，146 ng /μL），1μLA438079盐酸盐（3,30或300）在激光损伤后立即使用33号针头将相同体积的载体（PBS）加入玻璃体液中（ng /μL）。另一组小鼠注射3TC（125ng）与抗小鼠VEGF多克隆抗体（10ng）组合。山羊全IgG（10ng）用作抗小鼠VEGF抗体的生物对照。

[参考文献]

[1]. Gray LR, et al. The NRTIs lamivudine, stavudine and zidovudine have reduced HIV-1 inhibitory activity in astrocytes. PLoS One. 2013 Apr 16;8(4):e62196.

[2]. Hou P, et al. Genome editing of CXCR4 by CRISPR/cas9 confers cells resistant to HIV-1 infection. Sci Rep. 2015 Oct 20;5:15577.

[3]. Mizutani T, et al. Nucleoside Reverse Transcriptase Inhibitors Suppress Laser-Induced Choroidal Neovascularization in Mice. Invest Ophthalmol Vis Sci. 2015 Nov;56(12):7122-9.

[相关活性小分子]

齐多夫定物理化学性质

[ 熔点 ]:
113-115 °C(lit.)

[ 分子式 ]:
C₁₀H₁₃N₅O₄

[ 分子量 ]:
267.241

[ 精确质量 ]:
267.096741

[ PSA ]:
134.07000

[ LogP ]:
-0.53

[ 外观性状 ]:
白色至灰白色晶体

[ 折射率 ]:
47 ° (C=1, H2O)

[ 储存条件 ]:
通风低温干燥

[ 水溶解性 ]:
1-5 g/100 mL at 17 ºC

齐多夫定MSDS

详细MSDS(安全技术说明书)

齐多夫定毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: XP2072000

CHEMICAL NAME :: Thymidine, 3'-azido-3'-deoxy-

CAS REGISTRY NUMBER :: 30516-87-1

LAST UPDATED :: 199712

DATA ITEMS CITED :: 36

MOLECULAR FORMULA :: C10-H13-N5-O4

MOLECULAR WEIGHT :: 267.28

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 1 gm/kg/6W-I

TOXIC EFFECTS :: Skin and Appendages - nails

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 86 mg/kg/1W-I

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Behavioral - headache

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 434 mg/kg/38D-I

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

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Unreported

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 69 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - retinal changes (pigmentary depositions, retinitis, other)

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 3084 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - ptosis Behavioral - somnolence (general depressed activity)

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: >70 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 :: Unreported

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: >750 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 :: 3062 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - ptosis Behavioral - somnolence (general depressed activity)

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >70 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 :: Unreported

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >750 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 :: 54600 mg/kg/1Y-I

TOXIC EFFECTS :: Blood - pigmented or nucleated red blood cells Blood - changes in erythrocyte (RBC) count

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 91 gm/kg/26W-I

TOXIC EFFECTS :: Blood - normocytic anemia

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 47 gm/kg/94D-I

TOXIC EFFECTS :: Blood - pigmented or nucleated red blood cells Blood - changes in bone marrow (not otherwise specified) Blood - changes in erythrocyte (RBC) count

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 4700 mg/kg/94D-I

TOXIC EFFECTS :: Blood - pigmented or nucleated red blood cells Blood - changes in bone marrow (not otherwise specified) Blood - changes in erythrocyte (RBC) count

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 14500 mg/kg/29D-I

TOXIC EFFECTS :: Blood - pigmented or nucleated red blood cells Blood - changes in erythrocyte (RBC) count Blood - changes in leukocyte (WBC) count

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 6800 mg/kg/17D-I

TOXIC EFFECTS :: Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) Blood - pigmented or nucleated red blood cells Blood - changes in erythrocyte (RBC) count

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 7 gm/kg/2W-I

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 :: Oral

SPECIES OBSERVED :: Primate - monkey

DOSE/DURATION :: 3094 mg/kg/13W-I

TOXIC EFFECTS :: Blood - normocytic anemia

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Primate - monkey

DOSE/DURATION :: 18200 mg/kg/26W-I

TOXIC EFFECTS :: Blood - pigmented or nucleated red blood cells Blood - changes in other cell count (unspecified) Blood - changes in erythrocyte (RBC) count

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Primate - monkey

DOSE/DURATION :: 12740 mg/kg/1Y-I

TOXIC EFFECTS :: Blood - pigmented or nucleated red blood cells Blood - changes in erythrocyte (RBC) count Blood - changes in platelet count

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 4200 mg/kg

SEX/DURATION :: male 4 week(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland, accessory glands Reproductive - Paternal Effects - other effects on male

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 23 gm/kg

SEX/DURATION :: male 85 day(s) pre-mating female 26 day(s) pre-mating - 3 week(s) post-birth

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)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 69 gm/kg

SEX/DURATION :: male 85 day(s) pre-mating female 26 day(s) pre-mating - 3 week(s) post-birth

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Effects on Newborn - live birth index (measured after birth)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 27900 mg/kg

SEX/DURATION :: female 26 day(s) pre-mating - 15 day(s) post-birth

TOXIC EFFECTS :: Reproductive - Effects on Newborn - live birth index (measured after birth)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 910 mg/kg

SEX/DURATION :: female 1-13 day(s) after conception

TOXIC EFFECTS :: 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 :: Oral

DOSE :: 6500 mg/kg

SEX/DURATION :: female 6-18 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants)

TYPE OF TEST :: Micronucleus test

TYPE OF TEST :: Cytogenetic analysis

MUTATION DATA

TYPE OF TEST :: Sister chromatid exchange

TEST SYSTEM :: Rodent - hamster Ovary

DOSE/DURATION :: 500 mg/L

REFERENCE :: MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 321,113,1994

齐多夫定安全信息

[ 符号 ]:

GHS08

[ 信号词 ]:
Warning

[ 危害声明 ]:
H351

[ 警示性声明 ]:
P280

[ 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) ]:
Xn:Harmful

[ 风险声明 (欧洲) ]:
R40

[ 安全声明 (欧洲) ]:
S36/37/39-S45

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

[ WGK德国 ]:
3

[ RTECS号 ]:
XP2072000

[ 海关编码 ]:
2933990090

齐多夫定合成路线

详细合成路线

齐多夫定上下游产品

齐多夫定上游产品

齐多夫定下游产品

齐多夫定制备

胸腺嘧啶脱氧核苷和三苯基膦溶于二甲基甲酰胺中，缓慢滴入对甲氧基苯甲酸和偶氮二甲酸二乙酯(DEAD)溶于二甲基甲酰胺所成的溶液，在室温下搅拌后，再补加三苯基膦和DEAD。搅拌反应后，将反应液倒入乙醚，在0℃下放置过夜。过滤出的固体用小量乙醚洗，干燥，得酯化的氧桥物，收率84.1%。该氧桥物和叠氮钠在二甲基甲酰胺中，于125℃搅拌。冷到室温，将其倒入5%盐酸中，用醋酸乙酯提取。提取液用20%氯化钠溶液洗至中性，干燥，浓缩，真空干燥得叠氮衍生物，收率81.8%。叠氮衍生物和甲醇钠的甲醇溶液，在室温下搅拌后放置过夜。加入水，减压蒸去溶剂，再加水。用乙醚提取，往分出的水层中加入饱和氯化钠，放置过夜。冷至0℃过滤，滤饼用小量乙醇洗后，用水溶解，并用稀盐酸酸化至Ph=2。减压蒸除水，20%氯化钠洗，干燥，得类白色的齐多夫定固体，收率89.0%，熔点119.0～122.0℃。

齐多夫定海关

[ 海关编码 ]: 2933990090

[ 中文概述 ]:
2933990090. 其他仅含氮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, 乌洛托品请注明外观, 6－己内酰胺请注明外观, 签约日期

[ Summary ]:
2933990090. heterocyclic compounds with nitrogen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

齐多夫定文献

Xenobiotics that affect oxidative phosphorylation alter differentiation of human adipose-derived stem cells at concentrations that are found in human blood.

Dis. Model Mech. 8 , 1441-55, (2015)

Adipogenesis is accompanied by differentiation of adipose tissue-derived stem cells to adipocytes. As part of this differentiation, biogenesis of the oxidative phosphorylation system occurs. Many chem...

Evaluation of the in vitro/in vivo potential of five berries (bilberry, blueberry, cranberry, elderberry, and raspberry ketones) commonly used as herbal supplements to inhibit uridine diphospho-glucuronosyltransferase.

Food Chem. Toxicol. 72 , 13-9, (2014)

In this study, we evaluated inhibitory potentials of popularly-consumed berries (bilberry, blueberry, cranberry, elderberry, and raspberry ketones) as herbal supplements on UGT1A1, UGT1A4, UGT1A6, UGT...

Evaluation of thein vitro/in vivodrug interaction potential of BST204, a purified dry extract of ginseng, and its four bioactive ginsenosides through cytochrome P450 inhibition/induction and UDP-glucuronosyltransferase inhibition

Food Chem. Toxicol. 68 , 117-27, (2014)

• BST204 is a purified dry extract of ginseng containing high amounts of Rh2 and Rg3. • BST204 had only weak inhibitory effects on nine CYPs and five UGTs. • It is unlikely that BST204 alter pharmacok...

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