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Nocodazole

现货
Catalog No.
A8487
微管蛋白产生抑制剂,抗肿瘤剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 550.00
现货
10mg
¥ 500.00
现货
50mg
¥ 1,900.00
现货

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Background

Nocodazole, an anti-mitotic drug, is a rapidly-reversible inhibitor of microtubule polymerization which inhibits Abl, Abl(E255K) and Abl(T315I)with theIC50 value of 0.21 μM, 0.53 μM and 0.64 μM in cell-free assays, respectively[1].

In vitro: Nocodazolewas a high-affinity ligand for the cancer-related kinases including Abl phosphorylated, c-Kit, BRAF, and MEK with the Kd values of 0.091 μM, 1.6 μM, 1.8 μM and 1.6 μM, respectively. In addition, the Kd for Abl(E255K) phosphorylated, Abl(T315I) phosphorylated, BRAF(V600E) and PI3Kγ was 0.12 μM, 0.17 μM, 1.1 μM and 1.5 μM, respectively. In chronic lymphocytic leukemia cells, Nocodazole induced apoptosis. In some human colon carcinoma cells, Nocodazole decrease D apoptosis. Also, Nocodazole inhibited insulin-stimulated glucose transport. Nocodazole impaired the morphology and directionality of migrating medial gan-glionic eminence cells [1]. At high concentrations, Nocodazole rapidly depolymerized microtubules in cells, while low concentrations of Nocodazole inhibited microtubule dynamic instability [2].In SH-SY5Y cells, Nocodazole disrupted microtubules by binding to β-tubulin, prevented the formation of one of the two interchain disulfide linkages and impaired the transport of vesicles. Nocodazole significantly attenuated METH-induced cell death and lysosomal dysfunction [3]. Nocodazole (≥ 50 nM) resulted in a rapid reduction in fibroblast locomotion to a new rate that was maintained for > 2 hours. Nocodazole(100 nM) decreased the rate of locomotion by more than 60%; and 300 nM nocodazole completely stopped cell locomotion[4].

In vivo: In athymic mice bearing COLO 205 tumor xenografts,after 6 wk of treatment with Ketoconazole (50 mg/kg/three times per week)plus Nocodazole (5 mg/kg/three times per week), the antitumor effects of ND were significantly potentiated by KT. The tumor volume and tumor weight of the mice are significantly reduced as compared with those treated with Ketoconazole or Nocodazole alone. Nocodazole treatment in combination with Ketoconazole strongly enhanced apoptosis of COLO 205 tumor xenografts treated with Ketoconazole or Nocodazole alone [5].

References:
[1].  Park H, Hong S, Hong S. Nocodazole is a High‐Affinity Ligand for the Cancer‐Related Kinases ABL, c‐KIT, BRAF, and MEK[J]. ChemMedChem, 2012, 7(1): 53-56.
[2]. Xu K, Schwarz P M, Ludue a R F. Interaction of nocodazole with tubulin isotypes[J]. Drug development research, 2002, 55(2): 91-96.
[3]. Nara A, Aki T, Funakoshi T, et al. Hyperstimulation of macropinocytosis leads to lysosomal dysfunction during exposure to methamphetamine in SH-SY5Y cells[J]. Brain research, 2012, 1466: 1-14.
[4]. Liao G, Nagasaki T, Gundersen G G. Low concentrations of nocodazole interfere with fibroblast locomotion without significantly affecting microtubule level: implications for the role of dynamic microtubules in cell locomotion[J]. Journal of Cell Science, 1995, 108(11): 3473-3483.
[5]. Wang Y J, Jeng J H, Chen R J, et al. Ketoconazole potentiates the antitumor effects of nocodazole: In vivo therapy for human tumor xenografts in nude mice[J]. Molecular carcinogenesis, 2002, 34(4): 199-210.

文献引用

1. Wang H, Liu W, et al. "Inhibitor analysis revealed that clathrin-mediated endocytosis is involed in cellular entry of type III grass carp reovirus." Virol J. 2018 May 24;15(1):92. PMID:29793525

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt301.32
Cas No.31430-18-9
FormulaC14H11N3O3S
Solubility≥15.1mg/mL in DMSO
Chemical Namemethyl N-[6-(thiophene-2-carbonyl)-1H-benzimidazol-2-yl]carbamate
SDFDownload SDF
Canonical SMILESCOC(=O)NC1=NC2=C(N1)C=C(C=C2)C(=O)C3=CC=CS3
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验 [1]:

细胞系

SH-SY5Y细胞,NRK成纤维细胞

溶解方法

该化合物在DMSO中的溶解度大于15.1 mg/mL。若获取更高浓度的溶液,可在37℃下孵育10分钟,随后在超声波浴中摇匀。-20℃以下可储存数月。

反应条件

25-400 nM,1 μM,30 min

应用

在SH-SY5Y细胞中,Nocodazole(1 μM)通过结合β微管蛋白破坏微管,阻止两个链间二硫键中其中一个的形成,并阻碍囊泡的转运。Nocodazole显著减弱METH诱导的细胞死亡和溶酶体功能障碍。在大于2小时的Nocodazole治疗过程中,Nocodazole(400 nM)完全抑制细胞运动。Nocodazole以剂量依赖性方式降低运动速率。Nocodazole(25 nM、100 nM)显著抑制细胞运动。

动物实验 [2]:

动物模型

携带COLO 205肿瘤异种移植物的不孕小鼠

给药剂量

5 mg/kg,每周三次

应用

治疗6周后,nocodazole的抗肿瘤作用在小鼠中被ketoconazole显著增强。在接受这些治疗的小鼠中没有观察到毒性症状。

注意事项

由于实验环境的不同,实际溶解度可能与理论值略有不同,请测试室内所有化合物的溶解度。

References:

[1]. Liao G, Nagasaki T, Gundersen G G. Low concentrations of nocodazole interfere with fibroblast locomotion without significantly affecting microtubule level: implications for the role of dynamic microtubules in cell locomotion[J]. Journal of Cell Science, 1995, 108(11): 3473-3483.

[2]. Liao G, Nagasaki T, Gundersen G G. Low concentrations of nocodazole interfere with fibroblast locomotion without significantly affecting microtubule level: implications for the role of dynamic microtubules in cell locomotion[J]. Journal of Cell Science, 1995, 108(11): 3473-3483.

生物活性

Description Nocodazole is a potent and reversible inhibitor of tubulin production.
Targets tubulin          
IC50            

质量控制

化学结构

Nocodazole

相关生物数据

Nocodazole