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Cell Cycle/Checkpoint Aurora Kinase Tozasertib

Tozasertib

Catalog No. T2509   CAS 639089-54-6
Synonyms: VX 680, MK-0457

MK-0457 is a pan-Aurora kinase inhibitor (Kis: 0.6/18/4.6 nM for Aurora A/Aurora B/Aurora C). It shows selectivity against more than 190 different kinases.

Tozasertib, CAS 639089-54-6
Pack Size Availability Price/USD Quantity
10 mg In stock 36.00
25 mg In stock 58.00
50 mg In stock 70.00
100 mg In stock 110.00
200 mg In stock 154.00
250 mg In stock 166.00
1 mL * 10 mM (in DMSO) In stock 50.00
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Description MK-0457 is a pan-Aurora kinase inhibitor (Kis: 0.6/18/4.6 nM for Aurora A/Aurora B/Aurora C). It shows selectivity against more than 190 different kinases.
Targets&IC50 Aurora A :ic50 0.6nM(Kiapp),   Aurora B :ic50 18nM(Kiapp),   Aurora C :ic50 4.6nM(Kiapp),   Bcr-Abl :ic50 30nM(Ki),   FLT3 :ic50 30nM(Ki),  
In vitro Tozasertib (VX-680) is a potent inhibitor of all three Aurora kinases, with apparent inhibition constant (Ki(app)) values of 0.6, 18 and 4.6 nM for Aurora-A, Aurora-B, and Aurora-C, respectively. VX-680 caused accumulation of cells with 4N DNA content and potently inhibited the proliferation of a wide variety of tumor cell types with IC50 values ranging from 15 to 113 nM [1]. Treatment of the different ATC cells with VX-680 inhibited proliferation in a time- and dose-dependent manner, with the IC50 between 25 and 150 nM. The VX-680 significantly impaired the ability of the different cell lines to form colonies in soft agar. Analysis of caspase-3 activity showed that VX-680 induced apoptosis in the different cell lines [2].
In vivo In nude mice treated with VX-680 at 75 mg/kg, twice a day intraperitoneally (b.i.d. i.p.) for 13 d, mean tumor volumes were reduced by 98% in comparison with the control group. In four of ten animals, the final tumor volume was lower than the initial volume before treatment. Tumor growth reduction was dose-dependent and significant at a dose of 12.5 mg/kg b.i.d. VX-680 was well tolerated, with a small decrease in body weight observed only at the highest dose (5% decrease at 75 mg/kg b.i.d.). VX-680 also induced tumor regression in pancreatic and colon xenograft models. In an established human pancreatic (MIA PaCa-2) xenograft model, VX-680 at 50 mg/kg b.i.d i.p. induced regression in seven of ten tumors, with a 22% decrease in mean tumor volume relative to initial tumor size before treatment [1].
Kinase Assay Kinase inhibition assays: The consumption of ATP is coupled via the pyruvate kinase/lactic dehydrogenase enzyme pair to the oxidation of NADH, which can be monitored through the decrease in absorption at 340 nm. Reactions contains 100 mM Tris (pH 8), 10 mM MgCl2, 2.2 mM ATP, 1 mM phosphoenolpyruvate, 0.6 mg/mL NADH, 75 units/mL pyruvate kinase, 105 units/mL lactate dehydrogenase, and 0.5 mM substrate peptide (sequence: EAIYAAPFAKKK). Reactions (75 μL) are started by adding sufficient kinase to bring the reactions to 30 nM kinase concentration and the decrease in absorbance is monitored over 30 minutes at 30°C in a microtiter plate spectrophotometer. Inhibitory constants are obtained through addition of 3.75 μL VX-680 in 100% DMSO or DMSO alone. Ki values are calculated as follows, K i = IC50 / (1 + [S]/Kd), where [S] = [ATP] = 2.2 mM, and Kd (of ATP to Abl) = 70 μM. These values are calculated assuming a Kd (ATP) of 70 μM for wild type and H396P Abl kinase domain.
Cell Research
The CAL-62 cells are cultured in the absence (dimethyl sulfoxide, DMSO) or the presence of 500  nM VX-680 for different periods of time (1-5 days). The dose-dependent effects of VX-680 on cell proliferation are evaluated by treating the different ATC cells for 4 days with different concentrations of the Aurora inhibitor (5–500  nM). The cells are pulse labeled with 30  mM BrdU for 2  hours before the end of the incubation time. The BrdU incorporation is analyzed by means of a colorimetric immunoassay using the cell proliferation ELISA kit. The results from VX-680-treated cells are compared with those observed in control cells and expressed as a fold of variation versus control. (Only for Reference)
Cell lines: CAL-62 cells
Animal Research
Animal Model: Feathymic NCr-nu mice bearing HL-60 leukemia cells
Synonyms VX 680 , MK-0457
Purity 99.96%
Molecular Weight 464.59
Formula C23H28N8OS
CAS No. 639089-54-6

Storage

-20℃ 3 years powder

-80℃ 2 years in solvent

Solubility Information

DMSO: 46.5 mg/mL (100 mM)

( < 1 mg/ml refers to the product slightly soluble or insoluble )

Solution 1

30% PEG400+0.5% Tween80+5% propylene glycol: 30 mg/mL

Citations

References and Literature
1. Harrington EA, et al. VX-680, a potent and selective smallmolecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo. Nat Med. 2004; 10:262-7. 2. Arlot-Bonnemains Y, et al. Effects of the Aurora kinase inhibitor VX-680 on anaplastic thyroid cancer-derived cell lines. Endocr Relat Cancer. 2008 Jun;15(2):559-68.

Related compound libraries

This product is contained In the following compound libraries:
Approved Drug Library Bioactive Compound Library Inhibitor Library Anti-cancer Compound Library Clinical Compound Library Stem cell Differentiation Compound Library Autophagy Compound Library Epigenetics Compound Library Tyrosine kinase inhibitor library DNA Damage & Repair Compound Library Kinase Inhibitor Library Anti-cancer Approved drug Library Anti-cancer Clinical Compound Library Angiogenesis related Compound Library Preclinical Compound Library Cell cycle related Compound Library

Related Products

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SP-146 Aurora Kinase Inhibitor III SNS-314 Mesylate Aurora inhibitor 1 SCH-1473759 AZD1152 MBM-17S MBM-17

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