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Purity: ≥98%
Nocodazole (Oncodazole; R-17934; R17934) is a potent and rapidly-reversible inhibitor of microtubule polymerization/microtubule destablizer, the so called antimitotic or antitubulin agent, with potential antineoplastic activity. It also inhibits Abl, Abl(E255K) and Abl(T315I) with IC50 of 0.21 μM, 0.53 μM and 0.64 μM in cell-free assays, respectively. Nocodazole is used as an anti-cancer agent which exerts its effect in cells by interfering with the polymerization of microtubules. Nocodazole induces apoptosis in chronic lymphocytic leukemia cells. It inhibits insulin-stimulated glucose transport. Nocodazole decreases apoptosis in some human colon carcinoma cells.
| Targets |
Abl:91 nM (Kd); ABL(E255K):120 nM (Kd); ABL(T315I):170 nM (Kd); PI3Kγ:1.5 μM (Kd); BRAF:1.8 μM (Kd); MET:1.7 μM (Kd); BRAF(V600E):1.1 μM (Kd); c-KIT:1.6 μM (Kd); MEK1:1.7 μM (Kd); Microtubule/Tubulin CRISPR/Cas9; MEK2:1.6 μM (Kd);
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| ln Vitro |
In highly aggressive human cancer cells, nocodazole has a Kd value of 1.6 μM, indicating excellent affinity toward c-KIT. The mitogen-activated protein kinase (MAPK) pathway's constituents, including BRAF (Kd=1.8 μM), BRAF(V600E) (Kd=1.1 μM), MEK1 (Kd=1.7 μM), and MEK2 (Kd=1.6 μM), are well-bound by nocodazole[1]. Nocodazole promotes apoptosis in COLO 205 cancer cells at a concentration of 1 nM. It has the highest affinity for αβIV and the lowest affinity for αβIII[2]. The fraction of annexin-V-binding cells is dramatically increased by nocodazole (≥ 30 µg/mL) without appreciably altering the average forward scatter of human erythrocytes[4]. CHO cells are exposed to 1 nM nocodazole, a dose that inhibits microtubule dynamics, delays migration, and lengthens and increases the frequency of resting states while maintaining the directionality of the cells. The application of 70 nM Nocodazole, a concentration that destroys the microtubule network, reverses the effects of the low drug concentration and causes cells to migrate considerably more randomly, losing their directionality toward the wound[6].
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| ln Vivo |
Athymic mice with COLO 205 tumor xenografts have anticancer effects in response to nocodazole (5 mg/kg/three times per week, ip). The amounts of p21/CIP1 and p27/KIP1 protein in the tumor tissues are markedly increased by nocodazole (1 nM) + R-41400[3].
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| Enzyme Assay |
Nocodazole is an anti-mitotic drug that has long been used as an experimental tool in cell biology. Although nocodazole is known to bind with high affinity to tubulin and to inhibit microtubule assembly, very little has been done on its precise mechanism of action. In fact, its binding to the different isotypes of tubulin has never been addressed. Although the nocodazole binding site overlaps with that of colchicine, the two drugs are structurally quite different. The tubulin molecule is an α/β heterodimer; both α and β exist as various isotypes whose distribution and drug-binding properties are significantly different. In this study, we measured the binding affinity of nocodazole for purified tubulin isotypes. Using fluorescence quenching analysis, we found that the binding kinetics of nocodazole with each type of tubulin best fits a two-affinity Michaelis-Menten binding model. The apparent dissociation constants for the high-affinity binding sites are 0.52 ± 0.02 for αβII, 1.54 ± 0.29 for αβIII, and 0.29 ± 0.04 for αβIV. Thus, nocodazole has the highest affinity for αβIV and the lowest affinity for αβIII. Knowledge of the isotype specificity of nocodazole may allow for development of novel therapeutic agents based on this drug[2].
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| Cell Assay |
Flow cytometry was employed to determine phosphatidylserine exposure at the cell surface from annexin-V-binding, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, the abundance of reactive oxygen species (ROS) from 2',7'-dichlorodihydrofluorescein (DCF) diacetate dependent fluorescence as well as ceramide surface abundance utilizing specific antibodies. Tubulin abundance was quantified by TubulinTracker™ Green reagent and visualized by confocal microscopy[4].
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| References | |||
| Additional Infomation |
Nocodazole is a white powder. (NTP, 1992)
Nocodazole is a member of the class of benzimidazoles that is benzimidalole which is substituted at position 2 by a (methoxycarbonyl)amino group and at position 5 by a 2-thienoyl group. It is an antineoplastic agent that exerts its effect by depolymerising microtubules. It has a role as an antineoplastic agent, a tubulin modulator, an antimitotic and a microtubule-destabilising agent. It is a member of thiophenes, a member of benzimidazoles, a carbamate ester and an aromatic ketone. Nocodazole is an antineoplastic agent which exerts its effect by depolymerizing microtubules. Nocodazole is a synthetic tubulin-binding agent with antineoplastic activity. Nocodazole binds to beta-tubulin and disrupts microtubule assembly/disassembly dynamics. This prevents mitosis and induces apoptosis in tumor cells. Although nocodazole binding site overlaps with that of colchicine, the two agents are structurally quite different. Nocodazole is an antineoplastic agent which exerts its effect by depolymerizing microtubules. |
| Molecular Formula |
C14H11N3O3S
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| Molecular Weight |
301.32
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| Exact Mass |
301.052
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| Elemental Analysis |
C, 55.80; H, 3.68; N, 13.95; O, 15.93; S, 10.64
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| CAS # |
31430-18-9
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| Related CAS # |
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| PubChem CID |
4122
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| Appearance |
Light yellow to brown solid powder
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| Density |
1.5±0.1 g/cm3
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| Melting Point |
300 °C (dec.)
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| Index of Refraction |
1.732
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| LogP |
2.43
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
21
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| Complexity |
420
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
KYRVNWMVYQXFEU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C14H11N3O3S/c1-20-14(19)17-13-15-9-5-4-8(7-10(9)16-13)12(18)11-3-2-6-21-11/h2-7H,1H3,(H2,15,16,17,19)
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| Chemical Name |
methyl N-[6-(thiophene-2-carbonyl)-1H-benzimidazol-2-yl]carbamate
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.90 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2 mg/mL (6.64 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: 1% DMSO +30% polyethylene glycol+1% Tween 80 :30 mg/mL Solubility in Formulation 4: 5 mg/mL (16.59 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.3187 mL | 16.5937 mL | 33.1873 mL | |
| 5 mM | 0.6637 mL | 3.3187 mL | 6.6375 mL | |
| 10 mM | 0.3319 mL | 1.6594 mL | 3.3187 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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