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Tozasertib

Cat. No. M1881

Tozasertib Structure

Synonym: VX-680, MK-0457

Size Price Availability Quantity
50mg $150 In stock
100mg $250 In stock
200mg $350 In stock
1g $700 In stock
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Quality Control
Biological Activity

Tozasertib (VX-680, MK-0457) is a small-molecule Aurora kinase inhibitor. The Aurora kinases are essential for the regulation of chromosome segregation and cytokinesis during mitosis. Tozasertib (VX-680) blocks cell-cycle progression and induces apoptosis in a diverse range of human tumor types. Tozasertib (VX-680) effectively inhibits proliferation of several different cell lines of clear cell renal carcinoma (IC50s < 10 μM) and blocks the growth of tumors in a rodent model of cancer (80 mg/kg), inhibiting H3 histone phosphorylation, to an increase of apoptotic cells, and to morphological changes such as vacuolization and swelling of the cells and nuclei. The combination of VX-680 and histone deacetylase inhibitor SAHA had a synergistic effect on the proliferation of HUH6 cells. Tozasertib (VX-680) might improve treatment results in HB with increased Aurora kinase activity by inhibiting cell proliferation and induction of apoptosis.

Protocol
Cell Experiment
Cell lines SW620, K562, HL-60, MIA PaCa-2 and HCT116 cells
Preparation method Analysis of cell proliferation and viability.
Tumor cells were seeded in 96-well plates and incubated with VX-680 for 96 h. To measure DNA synthesis, 0.5 mCi of [3H]thymidine was added to each well 3 h before the end of the experiment. Cells were then collected, and the incorporated radioactivity was counted on a Wallac microplate beta-counter. Cell viability was assessed using Promega CellTiter 96AQ to measure MTS (3-(4,5 dimethylthiazol-2-yl)-5-(3- carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) conversion.
Concentrations 1~10 μM
Incubation time 96 h
Animal Experiment
Animal models female athymic NCr-nu mice HL-60, MIA PaCa-2 and HCT116 cells tumour xenograft model
Formulation 50% PEG 300 in 50 mM phosphate buffer
Dosages q.4.d. at a dose of 12.5, 25, 50 and 75 mg/kg
Administration i.v.
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
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 resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information
Molecular Weight 464.59
Formula C23H28N8OS
CAS Number 639089-54-6
Purity >98%
Solubility DMSO 90 mg/mL
Storage at -20°C
Chemical Name N-(4-(4-(5-methyl-1H-pyrazol-3-ylamino)-6-(4-methylpiperazin-1-yl)pyrimidin-2-ylthio)phenyl)cyclopropanecarboxamide
Customer Product Validation
Source Journal of Hematology & Oncology (2017). Figure 7. VX680 (Abmole Bioscience)
Method CCK8 assay
Cell Lines U251, U87 and U118 cell lines
Concentrations
Incubation Time 48 and 72 h
Results We found that the U251-SIX3 cells showed less sensitivity to VX680 compared with the U251-CON cells (Fig. 7a). With increased expression of AURKA or AURKB and reduced expression of SIX3, the p53 mutant U251 cells were more sensitive to VX680 treatment, compared with the p53 wild-type U87 cells (Fig. 7b).
Rating
Product Citations
References

In vitro evaluation of the Aurora kinase inhibitor VX-680 for Hepatoblastoma.
Dewerth A, et al. Pediatr Surg Int. 2012 Jun;28(6):579-89. PMID: 22526548.

Activity of the Aurora kinase inhibitor VX-680 against Bcr/Abl-positive acute lymphoblastic leukemias.
Fei F, et al. Mol Cancer Ther. 2010 May;9(5):1318-27. PMID: 20388735.

VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo.
Harrington EA, et al. Nat Med. 2004 Mar;10(3):262-7. PMID: 14981513.

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  Catalog
Abmole Inhibitor Catalog 2015




Keywords: Tozasertib, VX-680, MK-0457 supplier, Aurora Kinase, inhibitors

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