诺考达唑

诺考达唑用途

Nocodazole 是一种快速可逆的 microtubule 聚合抑制剂，也能够有效抑制ABL，ABL(E255K) 和 ABL(T315I) 的活性，IC₅₀ 值分别为 0.21 μM，0.53 μM 和 0.64 μM；同时可以增强 CRISPR/Cas9 的活性。

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诺考达唑名称

[ CAS 号 ]:
31430-18-9

[ 中文名 ]:
诺考达唑

[ 英文名 ]:
Nocodazole

[中文别名 ]:

诺考哒唑

[英文别名 ]:

Methyl N-(5-thenoyl-2-benzimidazolyl)carbamate
Nocodazole
Nocidazole
Methyl 5-(2-thienoyl)-2-benzimidazolecarbamate
nocodazolum
Nocodazol
EINECS 250-626-5
Oncodazole
MFCD00005588

诺考达唑生物活性

[ 描述 ]:

Nocodazole是快速可逆的 microtubule 抑制剂。 Nocodazole与β-微管蛋白结合并破坏微管组装/拆卸动力学,从而防止有丝分裂并诱导肿瘤细胞凋亡。

[ 相关类别 ]:

信号通路 >> 自噬 >> 自噬

信号通路 >> 蛋白酪氨酸激酶 >> BCR-ABL

信号通路 >> 细胞周期/DNA损伤 >> CRISPR/Cas9

信号通路 >> 细胞周期/DNA损伤 >> 微管/微管蛋白

信号通路 >> 细胞骨架 >> 微管/微管蛋白

研究领域 >> 癌症

[ 靶点 ]

Abl:91 nM (Kd)

ABL(E255K):120 nM (Kd)

ABL(T315I):170 nM (Kd)

BRAF:1.8 μM (Kd)

BRAF(V600E):1.1 μM (Kd)

c-KIT:1.6 μM (Kd)

MEK1:1.7 μM (Kd)

MEK2:1.6 μM (Kd)

MET:1.7 μM (Kd)

PI3Kγ:1.5 μM (Kd)

Microtubule/Tubulin

CRISPR/Cas9

[体外研究]

Nocodazole对c-KIT表现出良好的亲和力,在高度恶性的人癌细胞中Kd值为1.6μM。诺考达唑对促分裂原活化蛋白激酶(MAPK)途径的组分显示出良好的结合亲和力,例如BRAF(Kd =1.8μM),BRAF(V600E)(Kd =1.1μM),MEK1(Kd =1.7μM),和MEK2(Kd =1.6μM)[1]。 Nocodazole对αβIV的亲和力最高,对αβIII的亲和力最低[2]。从nocodazole阻滞释放后,有丝分裂同步的细胞对非常低浓度的紫杉醇敏感,持续<30分钟,即纺锤体形成所需的时间,但对长春碱保持敏感> 90分钟[3]。 Nocodazole(1 nM)诱导COLO 205癌细胞凋亡[4]。 Nocodazole(≥30μg/ mL)显着增加膜联蛋白-V结合细胞的百分比,而不显着改变人红细胞的平均前向散射[5]。

[体内研究]

Nocodazole(5mg/kg /每周三次,ip)在携带COLO205肿瘤异种移植物的无胸腺小鼠中具有抗肿瘤作用。 Nocodazole(1 nM)+酮康唑可显着增加肿瘤组织中p21/CIP1和p27/KIP1蛋白的水平[4]。

[细胞实验]

蛋白质以50μg/泳道加载，并用12％（w：v）十二烷基硫酸钠 - 聚丙烯酰胺凝胶电泳分离，印迹，并用抗体对细胞周期蛋白E，p53，p21 / CIP1，p27 / KIP1，甘油醛-3-磷酸进行探测。脱氢酶（GAPDH），细胞周期蛋白A，细胞周期蛋白D1，细胞周期蛋白D3，细胞周期蛋白B，CDK2，CDK4和细胞色素C.免疫反应条带通过与发色底物氮蓝四唑和5-溴-4-氯-3-吲哚 - 一起孵育而可视化。磷酸盐。 GAPDH的表达用作相等蛋白质加载的对照。

[动物实验]

COLO 205细胞在补充有10％FCS的RPMI 1640中生长。通过连续两次胰蛋白酶消化收获细胞，以300×g离心;保持5分钟，洗涤两次，并重悬于无菌磷酸盐缓冲盐水（PBS）中。将0.1mL的细胞（5×105）皮下注射到每只裸鼠的肩胛骨之间。移植后，用卡尺测量肿瘤大小，估计肿瘤体积。一旦肿瘤达到平均大小200 mm3，动物每周三次腹膜内注射DMSO（25μL），酮康唑（50 mg / kg），诺考达唑（5 mg / kg）或酮康唑+诺考达唑，持续6周。

[参考文献]

[1]. Park H, et al. Nocodazole is a high-affinity ligand for the cancer-related kinases ABL, c-KIT, BRAF, and MEK. ChemMedChem. 2012 Jan 2;7(1):53-6.

[2]. Keliang Xu, et al. Interaction of nocodazole with tubulin isotypes. Drug Development Research 2002

[3]. Long BH, et al. Paclitaxel inhibits progression of mitotic cells to G1 phase by interference with spindle formation without affecting other microtubule functions during anaphase and telephase. Cancer Res. 1994 Aug 15;54(16):4355-61.

[4]. Wang YJ, et al. Ketoconazole potentiates the antitumor effects of nocodazole: In vivo therapy for human tumor xenografts in nude mice. Mol Carcinog. 2002 Aug;34(4):199-210.

[5]. Signoretto E, et al. Nocodazole Induced Suicidal Death of Human Erythrocytes. Cell Physiol Biochem. 2016;38(1):379-92.

[6]. Zhang JP, et al. Efficient precise knockin with a double cut HDR donor after CRISPR/Cas9-mediated double-stranded DNA cleavage. Genome Biol. 2017 Feb 20;18(1):35.

[相关活性小分子]

诺考达唑物理化学性质

[ 密度 ]:
1.5±0.1 g/cm3

[ 熔点 ]:
300 °C (dec.)

[ 分子式 ]:
C₁₄H₁₁N₃O₃S

[ 分子量 ]:
301.320

[ 精确质量 ]:
301.052124

[ PSA ]:
112.32000

[ LogP ]:
2.43

[ 外观性状 ]:
琥珀色粉末

[ 折射率 ]:
1.732

[ 储存条件 ]:
2-8°C

[ 水溶解性 ]:
DMSO: 10 mg/mL, soluble

诺考达唑MSDS

详细MSDS(安全技术说明书)

诺考达唑毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: DD6521000

CHEMICAL NAME :: 2-Benzimidazolecarbamic acid, 5-(2-thenoyl)-, methyl ester

CAS REGISTRY NUMBER :: 31430-18-9

LAST UPDATED :: 199606

DATA ITEMS CITED :: 10

MOLECULAR FORMULA :: C14-H11-N3-O3-S

MOLECULAR WEIGHT :: 301.34

WISWESSER LINE NOTATION :: T56 BM DNJ CMVO1 GV- BT5SJ

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 :: 39530 ug/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 :: Intraperitoneal

DOSE :: 10 mg/kg

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

TOXIC EFFECTS :: Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea) Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Effects on Embryo or Fetus - fetal death

TYPE OF TEST :: Micronucleus test

TYPE OF TEST :: Micronucleus test

TYPE OF TEST :: Sex chromosome loss and nondisjunction

MUTATION DATA

TYPE OF TEST :: Sex chromosome loss and nondisjunction

TEST SYSTEM :: Mammal - species unspecified

DOSE/DURATION :: 2 ug/L

REFERENCE :: MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 201,423,1988

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诺考达唑安全信息

[ 符号 ]:

GHS08

[ 信号词 ]:
Warning

[ 危害声明 ]:
H341-H361d

[ 警示性声明 ]:
P281

[ 个人防护装备 ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ 危害码 (欧洲) ]:
T: Toxic;

[ 风险声明 (欧洲) ]:
R61

[ 安全声明 (欧洲) ]:
S53-S45-S36/37/39-S26

[ 危险品运输编码 ]:
2811

[ WGK德国 ]:
3

[ RTECS号 ]:
DD6521000

[ 包装等级 ]:
III

[ 危险类别 ]:
6.1(b)

[ 海关编码 ]:
2934999090

诺考达唑合成路线

详细合成路线

诺考达唑海关

[ 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%

诺考达唑文献

SHCBP1 is required for midbody organization and cytokinesis completion.

Cell Cycle 13(17) , 2744-51, (2014)

The centralspindlin complex, which is composed of MKLP1 and MgcRacGAP, is one of the crucial factors involved in cytokinesis initiation. Centralspindlin is localized at the middle of the central spind...

MeCP2 deficiency is associated with reduced levels of tubulin acetylation and can be restored using HDAC6 inhibitors.

J. Mol. Med. 93(1) , 63-72, (2015)

Rett syndrome (RTT) is a severe neurodevelopmental disorder, predominantly caused by loss of function mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene. Despite the genetic cause bei...

EphA receptors regulate prostate cancer cell dissemination through Vav2-RhoA mediated cell-cell repulsion.

Biol. Open 3(6) , 453-62, (2014)

Metastatic prostate cancer cells display EphB receptor-mediated attraction when they contact stromal fibroblasts but EphA-driven repulsion when they contact one another. The impact of these 'social' i...

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诺考达唑相关知识

诺考达唑_作用_生物活性_实验方法

2018-10-26 10:58:19

诺考达唑是微管聚合的合成抑制剂，在无细胞试验中也抑制Abl（IC50：0.21μM），Abl（E255K，IC50：0.53μM）和Abl（T315I，IC50：0.64μM）。诺考达唑与β-微管蛋白结合并破坏微管组装/拆卸动力学。一、诺考达唑的生物活性详解：1）体外活性诺考达唑对c-KIT表现...