Nocodazole

Names

[ Name ]:
Nocodazole

[Synonym ]:
2-Benzimidazolecarbamic acid, 5-(2-thienylcarbonyl)-, methyl ester
Methyl N-(5-thenoyl-2-benzimidazolyl)carbamate
methyl N-[6-(thiophene-2-carbonyl)-1H-benzimidazol-2-yl]carbamate
Methyl [5-(2-thienylcarbonyl)-1H-benzimidazol-2-yl]carbamate
Nocodazole
Nocidazole
2-Benzimidazolecarbamic acid, 5-(2-thienoyl)-, methyl ester
Methyl 5-(2-thienoyl)-2-benzimidazolecarbamate
nocodazolum
Nocodazol
methyl [5-(thiophen-2-ylcarbonyl)-1H-benzimidazol-2-yl]carbamate
EINECS 250-626-5
Carbamic acid, N-[5-(2-thienylcarbonyl)-1H-benzimidazol-2-yl]-, methyl ester
Oncodazole
MFCD00005588
methyl 5-(thiophene-2-carbonyl)-1H-benzo[d]imidazol-2-ylcarbamate

Biological Activity

[Description]:

Nocodazole 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.

[Related Catalog]:

Signaling Pathways >> Autophagy >> Autophagy

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> Bcr-Abl

Signaling Pathways >> Cell Cycle/DNA Damage >> CRISPR/Cas9

Signaling Pathways >> Cell Cycle/DNA Damage >> Microtubule/Tubulin

Signaling Pathways >> Cytoskeleton >> Microtubule/Tubulin

Research Areas >> Cancer

[Target]

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

[In Vitro]

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]. After release from the nocodazole block, cells synchronized in mitosis remaine sensitive to very low concentrations of paclitaxel for < 30 min, the time required for spindle formation, yet remains sensitive to vinblastine for > 90 min[3]. Nocodazole (1 nM) induces apoptosis of COLO 205 cancer cells[4]. Nocodazole (≥ 30 µg/mL) significantly increases the percentage of annexin-V-binding cells without significantly modifying average forward scatter of human erythrocytes[5].

[In Vivo]

Nocodazole (5 mg/kg/three times per week, i.p.) has antitumor effects in athymic mice bearing COLO 205 tumor xenografts. Nocodazole (1 nM) + ketoconazole dramatically increase the levels of p21/CIP1 and p27/KIP1 protein in the tumor tissues[4].

[Cell Assay]

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.

[Animal admin]

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), ketoconazole (50 mg/kg), nocodazole (5 mg/kg), or ketoconazole + nocodazole three times per week for 6 wk.

[References]

[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.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.5±0.1 g/cm3

[ Melting Point ]:
300 °C (dec.)

[ Molecular Formula ]:
C₁₄H₁₁N₃O₃S

[ Molecular Weight ]:
301.320

[ Exact Mass ]:
301.052124

[ PSA ]:
112.32000

[ LogP ]:
2.43

[ Index of Refraction ]:
1.732

[ Storage condition ]:
2-8°C

[ Water Solubility ]:
DMSO: 10 mg/mL, soluble

MSDS

Click to get detail MSDS

Toxicological Information

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

Safety Information

[ Symbol ]:

GHS08

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H341-H361d

[ Precautionary Statements ]:
P281

[ Personal Protective Equipment ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ Hazard Codes ]:
T: Toxic;

[ Risk Phrases ]:
R61

[ Safety Phrases ]:
S53-S45-S36/37/39-S26

[ RIDADR ]:
2811

[ WGK Germany ]:
3

[ RTECS ]:
DD6521000

[ Packaging Group ]:
III

[ Hazard Class ]:
6.1(b)

[ HS Code ]:
2934999090

Synthetic Route

Click to get detail synthetic route

Customs

[ HS Code ]: 2934999090

[ Summary ]:
2934999090. other heterocyclic compounds. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

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