NocodazoleNocodazole
MedChemExpress (MCE)
HY-13520
31430-18-9
Oncodazole
R17934
99.59%
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
Room temperature in continental US
may vary elsewhere.
Nocodazole (Oncodazole) is a rapidly-reversible inhibitor of microtubule. Nocodazole binds to β-tubulin and disrupts microtubule assembly/disassembly dynamics, which prevents mitosis and induces apoptosis in tumor cells. Nocodazole inhibits Bcr-Abl, and activates CRISPR/Cas9.
Nocodazole exhibits good affinity toward c-KIT, with a Kd value of 1.6 μM in highly malignant human cancer cells. Nocodazole displays good binding affinity toward the components of the mitogen-activated protein kinase (MAPK) pathway, such as BRAF (Kd=1.8 μM), BRAF(V600E) (Kd=1.1 μM), MEK1 (Kd=1.7 μM), and MEK2 (Kd=1.6 μM)[1]. Nocodazole has the highest affinity for αβIV and the lowest affinity for αβIII[2]. Nocodazole (1 nM) induces apoptosis of COLO 205 cancer cells[3]. Nocodazole (≥ 30 µg/mL) significantly increases the percentage of annexin-V-binding cells without significantly modifying average forward scatter of human erythrocytes[4]. In CHO cells, the addition of 1 nM Nocodazole, a concentration that suppresses microtubule dynamics, slows migration and increases the frequency and duration of resting states, but the directionality of the cells is maintained. In contrast to the effects of the low drug concentration, the addition of 70 nM Nocodazole, a concentration that eliminates the microtubule network, causes cells to move much more randomly, i.e., the directionality of the cells toward the wound is lost[6].
Nocodazole (5 mg/kg/three times per week, i.p.) has antitumor effects in athymic mice bearing COLO 205 tumor xenografts. Nocodazole (1 nM) + R-41400 dramatically increase the levels of p21/CIP1 and p27/KIP1 protein in the tumor tissues[3].
COLO 205 cells are grown in RPMI 1640 supplemented with 10% FCS. Cells are harvested through two consecutive trypsinizations, centrifuged at 300×g
for 5 min, washed twice, and resuspended in sterile phosphate-buffered saline (PBS). Cells (5×105) in 0.1 mL are injected subcutaneously between the scapulae of each nude mouse. After transplantation, tumor size is measured with calipers, and the tumor volume is estimated. Once tumors reach a mean size of 200 mm3, animals receive intraperitoneal injections of DMSO (25 μL), R-41400 (50 mg/kg), nocodazole (5 mg/kg), or R-41400 + nocodazole three times per week for 6 wk.
Proteins are loaded at 50 μg/lane and separated by 12% (w:v) sodium dodecyl sulfate-polyacrylamide gel electrophoresis, blotted, and probed with antibodies for cyclin E, p53, p21/CIP1, p27/KIP1, glyceraldehyde 3-phosphate dehydrogenase (GAPDH), cyclin A, cyclin D1, cyclin D3, cyclin B, CDK2, CDK4, and cytochrome C. Immunoreactive bands are visualized by incubating with the colorigenic substrates nitroblue tetrazolium and 5-bromo-4-chloro-3-indolyl-phosphate. The expression of GAPDH is used as the control for equal protein loading.
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
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[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. [Content Brief]
[2]. Keliang Xu, et al. Interaction of nocodazole with tubulin isotypes. Drug Development Research 2002
[3]. Wang YJ, et al. R-41400 potentiates the antitumor effects of nocodazole: In vivo therapy for human tumor xenografts in nude mice. Mol Carcinog. 2002 Aug
34(4):199-210. [Content Brief]
[4]. Signoretto E, et al. Nocodazole Induced Suicidal Death of Human Erythrocytes. Cell Physiol Biochem. 2016
38(1):379-92. [Content Brief]
[5]. 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. [Content Brief]
[6]. Anutosh Ganguly, et al. The role of microtubules and their dynamics in cell migration. J Biol Chem. 2012 Dec 21
287(52):43359-69. [Content Brief]
