产品说明书

Tozasertib

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Chemical Structure| 639089-54-6 同义名 : VX 680;MK-0457;VE465
CAS号 : 639089-54-6
货号 : A153482
分子式 : C23H28N8OS
纯度 : 99%+
分子量 : 464.586
MDL号 : MFCD13185152
存储条件：

粉末 Sealed in dry,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 100 mg/mL(215.25 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

5% DMSO+30% PEG 300+2% Tween 80+water 15 mg/mL

生物活性
靶点

  • Aurora A

    Aurora A, Ki app:0.6 nM

  • Aurora B

    Aurora B, Ki app:18 nM

  • Aurora C

    Aurora C, Ki app:4.6 nM
描述 The Aurora family of serine/threonine kinases, which consists of Aurora A, B and C, plays an important role in chromosome alignment, segregation, and cytokinesis during mitosis. Tozasertib is a potent inhibitor of all three Aurora kinases, with Ki(app) values of 0.6 nM, 18 nM and 4.6 nM for Aurora A, B and C, respectively, and showed much less potency to FLT3 and Bcr-Abl with Ki(app) values of 30 nM. Tozasertib potently inhibited the proliferation of a wide variety of tumor cell types from different original tissues with IC50 values ranging in 15-113 nM, including HCT116, LS174T (colorectal), HL60 (leukemia), MD-MBA-231, ZR-75-1, MCF-7 (breast), PC3 (prostate), MIA PaCa2 (pancreatic), A375 (melanoma) and HeLa (cervical). In a further study, it was found that leukemia, lymphoma and colorectal cancer cell lines were particularly sensitive to Tozasertib on growth inhibition attributable to apoptosis. Tozasertib can cause accumulation of HeLa cells with ≥4N DNA content and inhibits histone H3 phosphorylation on Ser10, suggesting the inhibition of Aurora B. These can also be observed in in vivo model. Tozasertib at 75 mg/kg, twice a day intraperitoneally, caused mean tumor volumes reduced by 98% in a human AML (HL-60) xenograft model. Administration of Tozasertib by i.v. infusion at 1 mg/kg/h, 3 d per week, caused tumor regression in four of seven nude rats bearing established HCT116 (colon) tumors[1].
作用机制 Tozasertib binds to the ATP-binding site of the Aurora kinases.[1]
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
697 Growth Inhibition Assay IC50=0.02471 μM SANGRER
8-MG-BA Growth Inhibition Assay IC50=9.32844 μM SANGRER
A101D Growth Inhibition Assay IC50=1.87395 μM SANGRER
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT00500006 Chronic Myelogenous Leukemia ... 展开 >> Leukemia, Lymphoblastic, Acute, Philadelphia-Positive 收起 << Phase 1 Terminated - -
NCT00405054 Leukemia Phase 2 Terminated - -
NCT00290550 Carcinoma, Non-Small-Cell Lung Phase 2 Terminated - -
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.15mL

0.43mL

0.22mL

10.76mL

2.15mL

1.08mL

21.52mL

4.30mL

2.15mL
参考文献

[1]Harrington EA, Bebbington D, et al. VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo. Nat Med. 2004 Mar;10(3):262-7. Epub 2004 Feb 22.

[2]Winter GE, Rix U, et al. An integrated chemical biology approach identifies specific vulnerability of Ewing's sarcoma to combined inhibition of Aurora kinases A and B. Mol Cancer Ther. 2011;10(10):1846-56.