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Tozasertib

Catalog No. T2509 CAS 639089-54-6

Synonyms: MK-0457, VX 680

Tozasertib (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.

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Tozasertib, CAS 639089-54-6

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50 mg	In stock	$ 62.00
100 mg	In stock	$ 101.00
1 mL * 10 mM (in DMSO)	In stock	$ 50.00

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Purity: 99.96%

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Description	Tozasertib (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:0.6 nM (Ki), Aurora B:18 nM (Ki), Aurora C:4.6 nM (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	Recombinant Aurora-1 (62-344), Aurora-2 (1-403) and Aurora-3 (1-309) were expressed as N-terminal, His6-tagged fusion proteins using a baculovirus expression system. The proteins were purified by affinity chromatography using Ni-NTA agarose, followed by size exclusion using a Superdex 200 26/60 column. Inhibition of kinase activity was assessed using a standard enzyme-coupled system or a radiometric, phosphocellulose-peptide capture assay as previously described [1].
Cell Research	Logarithmically growing MCF-7 cells were incubated with either VX-680 or DMSO for 48 h. Single-cell suspensions were fixed in 70% ethanol for 15 min, incubated with RNase (1 mg/ml) at 37 °C for 30 min, labeled with 400 μl propidium iodide (50 μg/ml) for at least 15 min at room temperature. Cell-cycle profiles were determined by flow cytometric analysis [1].
Animal Research	For the HL-60 study, female athymic NCr-nu mice were inoculated subcutaneously with 10^7 HL-60(TB) leukemia cells into the right axillary area. Treatment was administered i.p. b.i.d. after tumors reached 150–200 mm^3. VX-680 was prepared in a vehicle of 50% PEG 300 in 50 mM phosphate buffer. Cisplatin, formulated in saline, was administered i.p. q.4.d. for a total of three injections, at a dose of 5.4 mg/kg. For the MIA PaCa-2 studies, female MF1 nude mice were inoculated with 10^7 MIA PaCa-2 cells into the dorsal flank. Treatment was administered i.p. b.i.d. after tumors reached 175 mm^3. VX-680 was prepared in a vehicle of 50% PEG 300 in 50 mM phosphate buffer. 5-fluorouracil, formulated in saline, was administered i.v. q.4.d. at a dose of 50 mg/kg. For the HCT116 study, female Hsd RH rnu/nu rats were inoculated with 10^7 HCT116 cells into the right flank. Treatment was administered once the tumors reached 700–950mm^3. VX-680 was administered continuously through an indwelling femoral catheter, followed by a saline infusion for 4 d before repeating the dose cycle. For all studies, tumor volume was determined by caliper measurements three times a week [1].

Synonyms	MK-0457, VX 680
Molecular Weight	464.59
Formula	C23H28N8OS
CAS No.	639089-54-6

Storage

Powder: -20°C for 3 years | In solvent: -80°C for 1 year

Solubility Information

DMSO: 46.5 mg/mL (100 mM)

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.

Citations

1. Cheng S, Jin P, Li H, et al. Evaluation of CML TKI Induced Cardiovascular Toxicity and Development of Potential Rescue Strategies in a Zebrafish Model. Frontiers in Pharmacology. 2021: 2866. 2. Shao Y, Li H, Wu Y, et al.The feedback loop of AURKA/DDX5/TMEM147-AS1/let-7 drives lipophagy to induce cisplatin resistance in epithelial ovarian cancer.Cancer Letters.2023: 216241.

Related compound libraries

This product is contained In the following compound libraries：

Inhibitor Library Drug Repurposing Compound Library Anti-Cancer Drug Library Anti-Cancer Approved Drug Library Tyrosine Kinase Inhibitor Library FDA-Approved Kinase Inhibitor Library Highly Selective Inhibitor Library Anti-Cancer Active Compound Library Anti-Cancer Clinical Compound Library Kinase Inhibitor Library

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Keywords

Tozasertib 639089-54-6 Autophagy Cell Cycle/Checkpoint Chromatin/Epigenetic Aurora Kinase VX680 inhibit Inhibitor VX-680 MK0457 MK-0457 MK 0457 VX 680 inhibitor

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