| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 100mg |
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| 250mg |
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Purity: ≥98%
Tozasertib (formerly VX-680; MK-0457) is a novel and potent pan-Aurora kinase (AK) inhibitor with potential anticancer activity. It inhibits Aurora kinase A (AKA) with a Kiapp of 0.6 nM in a cell-free assay, and is less potent towards Aurora B/Aurora C. It shows 100-fold higher selectivity for Aurora A over 55 other kinases with Kis of 0.6, 18, 4.6 nM for Aurora B/C kinases, respectively. Tozasertib exhibited potent in vitro antiproliferative activity and high in vivo antitumor efficacy. VX680 was discovered through a molecular screening campaign and is a potent inhibitor of pan-aurora kinase as well as other kinases including Src, GSK3β, Flt3, JAK2, BCR-Abl (wild type) and BCR-Abl (T315I mutant). It binds to the inactive conformations of non-aurora kinases preventing activation, which leads to the inhibition of a wide array of kinases.
| ln Vitro |
When BaF3 cells transfected with ABL or FLT-3 (mutant and wild-type) kinases are exposed to tozasertib, the cells show G2/M arrest, endoreduplication, and apoptosis in addition to comparable cytotoxicity (IC50 of about 300 nM). suppressor phenotype akin to AUR B. Time-dependently, tozasertib inhibits the growth of CAL-62. The number and size of colonies was dramatically decreased by about 70% for 8305C and by 90% for CAL-62, 8505C, and BHT-101 after 14 days of tozasertib treatment. Different ATC cell lines were treated with tozasertib, which decreased growth with an IC50 ranging from 25 to 150 nM. Tozasertib dramatically reduces many cell lines' capacity to establish colonies in soft agar. Analyses of Caspase-3 activity revealed that Tozasertib caused apoptosis in many cell types. After being exposed to tozasertib for 12 hours, CAL-62 cells accumulated cells with a DNA content of less than 4N. Time-lapse imaging revealed that Tozasertib-treated CAL-62 cells exit metaphase without proliferating. Moreover, the administration of tozasertib results in the elimination of histone H3 phosphorylation [2]. In patient-derived samples, tozasertib significantly inhibits BCR-Abl with the T315I mutation [3].
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| ln Vivo |
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| Animal Protocol |
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| References |
[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]. Salah E, et al. Crystal structures of ABL-related gene (ABL2) in complex with imatinib, tozasertib (VX-680), and a type I inhibitor of the triazole carbothioamide class.J Med Chem. 2011 Apr 14;54(7):2359-67. Epub 2011 Mar 18. [3]. 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 |
| Molecular Formula |
C23H28N8OS
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| Molecular Weight |
464.59
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| CAS # |
639089-54-6
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| Related CAS # |
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| SMILES |
O=C(C1CC1)NC2=CC=C(SC3=NC(NC4=CC(C)=NN4)=CC(N5CCN(C)CC5)=N3)C=C2
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| InChi Key |
GCIKSSRWRFVXBI-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H28N8OS/c1-15-13-20(29-28-15)25-19-14-21(31-11-9-30(2)10-12-31)27-23(26-19)33-18-7-5-17(6-8-18)24-22(32)16-3-4-16/h5-8,13-14,16H,3-4,9-12H2,1-2H3,(H,24,32)(H2,25,26,27,28,29)
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| Chemical Name |
(N-[4({4-(4-methylpiperazin-1-yl)-6-[(3-methyl-1H-pyrazol-5 -yl)amino]pyrimidin-2-yl}thio)phenyl]cyclopropanecarboxamide)
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| Synonyms |
Tozasertib, MK-0457; VX-680; MK 0457; MK-0457; VX680; VX 680; MK0457; VE 465; VE465; VE-465
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.48 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.48 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.48 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 30% PEG400+0.5% Tween80+5% propylene glycol:30mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1524 mL | 10.7622 mL | 21.5244 mL | |
| 5 mM | 0.4305 mL | 2.1524 mL | 4.3049 mL | |
| 10 mM | 0.2152 mL | 1.0762 mL | 2.1524 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT02532868 | Terminated | Drug: MK-0457 | Cancer | Merck Sharp & Dohme LLC | May 2005 | Phase 1 |
| NCT00099346 | Terminated | Drug: MK0457, VX-680 (Aurora Kinase Inhibitor) |
Colorectal Cancer Advanced Solid Tumors |
Merck Sharp & Dohme LLC | January 2005 | Phase 1 |
ABL2 bound to a type I inhibitor2. (A) ABL2:2, showing the compound bound to the ATP binding site, and the ordered activation loop. Compound2is shown in yellow.J Med Chem.2011 Apr 14;54(7):2359-67. |
Myristate binding pocket of ABL2. (A) Surface of the myristate binding pocket of ABL2, with imatinib shown as a yellow ball-and-stick representation.J Med Chem.2011 Apr 14;54(7):2359-67. |
Comparison of ABL2:imatinib and ABL2:1with ABL1:imatinib and ABL1:1.J Med Chem.2011 Apr 14;54(7):2359-67. |
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