| 包装 | 价格(元) |
| 10mM (in 1mL DMSO) | 电议 |
| 50mg | 电议 |
| 100mg | 电议 |
| 250mg | 电议 |
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 contained 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) were started by adding sufficient kinase to bring the reactions to 30 nM kinase concentration and the decrease in absorbance was monitored over 30 mins at 30 ℃ in a microtiter plate spectrophotometer. Inhibitory constants were obtained through addition of 3.75 μL VX-680 in 100% DMSO or DMSO alone. Ki values were calculated as follows, Ki = IC50 / (1 + [S]/Kd), where [S] = [ATP] = 2.2 mM, and Kd (of ATP to Abl) = 70 μM. These values were calculated assuming a Kd (ATP) of 70 μM for wild type and H396P Abl kinase domain. |
Cell lines | CAL-62 cells |
Preparation method | The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20 ℃ for several months. |
Reaction Conditions | 5 ~ 500 nM; 4 days |
Applications | VX-680 prevented the CAL-62 proliferation in a time-dependent manner. |
Animal models | Female athymic NCr-nu mice bearing HL-60 leukemia cells |
Dosage form | 12.5, 25, 50 or 70 mg/kg; i.p.; b.i.d., for 13 days |
Applications | In female athymic NCr-nu mice bearing HL-60 leukemia cells, VX-680 (70 mg/kg; i.p.; b.i.d., for 13 days) reduced the tumor volume by 98%. |
Other notes | Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
| 产品描述 | Tozasertib (VX 680; MK-0457) is an inhibitor of Aurora A/B/C kinases with Kis of 0.6, 18, 4.6 nM, respectively. Tozasertib induces similar cytotoxicity with IC50 of approximately 300 nM and exhibits an AUR B-like inhibitory phenotype of G2/M arrest, endoreduplication and apoptosis in BaF3 cells transfected with ABL or FLT-3 (mutant and wild type) kinases. Tozasertib prevents the CAL-62 proliferation in a time-dependent manner. Tozasertib treatment for 14 days significantly decreases the number and size of colonies by approximately 70% in the 8305C and 90% in the CAL-62, 8505C and BHT-101. Treatment of the different ATC cells with Tozasertib inhibits proliferation with the IC50 between 25 and 150 nM. The Tozasertib significantly impairs the ability of the different cell lines to form colonies in soft agar. Analysis of caspase-3 activity indicates that Tozasertib induces apoptosis in the different cell lines. CAL-62 cells exposed for 12 hours to Tozasertib show an accumulation of cells with ≥ 4N DNA content. Time-lapse analysis demonstrates that Tozasertib-treated CAL-62 cells exit metaphase without dividing. Moreover, histone H3 phosphorylation is abrogated following Tozasertib treatment[2]. Tozasertib has significant inhibitory activity against BCR-Abl bearing the T315I mutation in patient-derived samples[3]. References: |
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