Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Tozasertib (MK-0457) 是一种 Aurora A/B/C 激酶抑制剂,Ki 值分别为 0.6、18和4.6 nM。它显示出对 190 多种不同激酶的选择性。
规格 | 价格/CNY | 货期 | 数量 | |
---|---|---|---|---|
10 mg | ¥ 348 | 现货 | ||
25 mg | ¥ 668 | 现货 | ||
50 mg | ¥ 996 | 现货 | ||
100 mg | ¥ 1,730 | 现货 | ||
200 mg | ¥ 2,440 | 现货 | ||
1 mL * 10 mM (in DMSO) | ¥ 227 | 现货 |
产品描述 | 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. |
靶点活性 | Aurora A:0.6 nM (Ki), Aurora B:18 nM (Ki), Aurora C:4.6 nM (Ki) |
体外活性 | 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]. |
体内活性 | 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]. |
激酶实验 | 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]. |
细胞实验 | 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]. |
动物实验 | 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]. |
别名 | MK-0457, VX 680 |
分子量 | 464.59 |
分子式 | C23H28N8OS |
CAS No. | 639089-54-6 |
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
DMSO: 46.5 mg/mL (100 mM)
可选溶剂 | 浓度 体积 质量 | 1 mg | 5 mg | 10 mg | 25 mg |
DMSO | 1 mM | 2.1524 mL | 10.7622 mL | 21.5244 mL | 53.8109 mL |
5 mM | 0.4305 mL | 2.1524 mL | 4.3049 mL | 10.7622 mL | |
10 mM | 0.2152 mL | 1.0762 mL | 2.1524 mL | 5.3811 mL | |
20 mM | 0.1076 mL | 0.5381 mL | 1.0762 mL | 2.6905 mL | |
50 mM | 0.043 mL | 0.2152 mL | 0.4305 mL | 1.0762 mL | |
100 mM | 0.0215 mL | 0.1076 mL | 0.2152 mL | 0.5381 mL |
对于不同动物的给药剂量换算,您也可以参考 更多...
请在以下方框中输入您的动物实验信息后点击计算,可以得到母液配置方法和体内配方的制备方法: 比如您的给药剂量是10 mg/kg,每只动物体重20 g,给药体积100 μL,一共给药动物10 只,您使用的配方为5% DMSO+30% PEG300+5% Tween 80+60% ddH2O。那么您的工作液浓度为2 mg/mL。
母液配置方法:2 mg 药物溶于 50 μL DMSO (母液浓度为 40 mg/mL), 如您需要配置的浓度超过该产品的溶解度,请先与我们联系。
体内配方的制备方法:取 50 μL DMSO 主液,加入 300 μL PEG300, 混匀澄清,再加 50 μL Tween 80,混匀澄清,再加 600 μL ddH2O, 混匀澄清。
您可能有的问题的答案可以在抑制剂处理说明中找到,包括如何准备库存溶液,如何存储产品,以及基于细胞的分析和动物实验需要特别注意的问题。
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