Nocodazole

Biological Activity

Nocodazole is an anti-microtubule agent for ABL, ABL (E255K) and ABL (T315I) with IC50 of 0.21 μM, 0.53 μM and 0.64 μM, respectively. Nocodazole is a high-affinity ligand for the cancer-related kinases including ABL phosphorylated, c-KIT, BRAF, and MEK with Kd of 0.091 μM, 1.6 μM, 1.8 μM and 1.6 μM, respectively. In addition, the Kd of Nocodazole for ABL (E255K) phosphorylated, ABL (T315I) phosphorylated, BRAF (V600E) and PI3Kγ is 0.12 μM, 0.17 μM, 1.1 μM and 1.5 μM, respectively. Nocodazole induces apoptosis in chronic lymphocytic leukemia cells. Nocodazole inhibits insulin-stimulated glucose transport. Nocodazole decreases apoptosis in some human colon carcinoma cells. Nocodazole impairs the morphology and directionality of migrating medial gan-glionic eminence cells. At high concentrations, nocodazole rapidly depolymerizes microtubules in cells, while low concentrations of nocodazole inhibit microtubule dynamic instability. Mitotic cells incubated with different concentrations of paclitaxel are inhibited from progressing to G1 phase 6 hours after release from the nocodazole block, with a median inhibitory concentration of 4 nM. Nocodazole-pretreated cells exposed to paclitaxel in the absence of nocodazole only form free-floating microtubules, whereas pretreated cells exposed to paclitaxel in the presence of nocodazole-assembled centrosome organize microtubules. Nocodazole disrupts microtubules by binding to β-tubulin. Nocodazole prevents the formation of one of the two interchain disulfide linkages. Nocodazole impairs the transport of vesicles. Nocodazole suppress METH-induced cell death and lysosomal dysfunction. METH-induced cell death is significantly decreased by Nocodazole pretreatment in comparison to METH alone. The tumor volume and tumor weight of the mice treated with Ketoconazole  plus  Nocodazole are significantly reduced as compared with those treated with Ketoconazole or Nocodazole alone. Combined treatment with Ketoconazole  plus  Nocodazole strongly enhances apoptosis of COLO 205 tumor xenografts treated with Ketoconazole  or  Nocodazole alone. The tumor volume and tumor weight of the mice treated with Ketoconazole  plus  Nocodazole are significantly reduced as compared with those treated with Ketoconazole or Nocodazole alone. Combined treatment with Ketoconazole  plus  Nocodazole strongly enhances apoptosis of COLO 205 tumor xenografts treated with Ketoconazole  or  Nocodazole alone.

Product Citations

• 

  Mol Cell. 2023 Mar 8;S1097-2765(23)00113-2.

  Sequence and chromatin features guide DNA double-strand break resection initiation
  Nocodazole purchased from AbMole

• 

  Elife. 2023 Jun 30;12:e84322.

  Long-range DNA end resection supports homologous recombination by checkpoint activation rather than extensive homology generation
  Nocodazole purchased from AbMole

• 

  Nat Methods. 2022 Mar;19(3):331-340.

  Efficient targeted insertion of large DNA fragments without DNA donors
  Nocodazole purchased from AbMole

Protocol (for reference only)

Cell Experiment
Cell lines
Preparation method
Concentrations
Incubation time

Animal Experiment
Animal models	Nude mice with COLO-205 tumor xenografts
Formulation	0.05% dimethyls
Dosages	5 mg/kg
Administration	Administered via i.p.

Chemical Information

Molecular Weight	301.32
Formula	C14H11N3O3S
CAS Number	31430-18-9
Solubility (25°C)	DMSO 12 mg/mL
Storage	Powder          -20°C   3 years ;  4°C   2 years In solvent       -80°C   6 months ;  -20°C   1 month

Conversion of different model animals based on BSA (PMID: 27057123)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

References

[1] Arif A Surani, et al. Optimizing Cell Synchronization Using Nocodazole or Double Thymidine Block

[2] S M Attia, et al. Dominant lethal effects of nocodazole in germ cells of male mice

[3] Hoi Tang Ma, et al. Synchronization of HeLa cells

[4] Kingo Endo, et al. Nocodazole induces mitotic cell death with apoptotic-like features in Saccharomyces cerevisiae

[5] Stephen Cooper, et al. Nocodazole does not synchronize cells: implications for cell-cycle control and whole-culture synchronization