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Anti-mitotic agent and aurora kinase inhibitor combination as anti-cancer treatment

An anti-mitotic agent, inhibitor technology, applied in the direction of drug combination, organic active ingredients, medical preparations containing active ingredients, etc.

Inactive Publication Date: 2010-08-18
SCHERING AG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The following paragraphs describe anti-mitotic agents and laser kinase inhibitors in more detail

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  • Anti-mitotic agent and aurora kinase inhibitor combination as anti-cancer treatment
  • Anti-mitotic agent and aurora kinase inhibitor combination as anti-cancer treatment
  • Anti-mitotic agent and aurora kinase inhibitor combination as anti-cancer treatment

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[1705] Asynchronous cells need 24 hours to be exposed to laser kinase inhibitors (such as 250nM VX-680 or 1000nM compound X (compound X is disclosed in WO2008 / 057512 of application on November 6, 2007, in examples 4-3 and claim 70 , Embodiments 4-3 and claim 70 are shown below, and it is represented by the formula H of the present application and the 2nd column column 17 of Table 2) or 25nM compound Z (compound Z is disclosed on June 11, 2008 and proposed Application PCT US2008 / 007295, embodiment 76-2 and claim 25, column 7, column 4, and it is represented by compound 76-2 in Table 13 of the present application)) to induce nuclear replication (> 4N DNA content ) or cell death. For example, HCT-116 colon cancer cells were treated with 1000 nM Compound X or 25 nM Compound Z for the indicated times, at which point the drug was washed out and replaced with fresh medium, see respectively figure 1 and Figure 8 . After a total of 72 hours, cells were analyzed by FACS. Exposure f...

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Abstract

The present invention relates to a method of treating cancer by pretreatment with anti-mitotic agents followed by at least one aurora kinase inhibitor. Extensive illustrations are provided for the antimitotic agents and aurora kinase inhibitors that are useful in the inventive treatment.

Description

technical field [0001] The present invention relates to a method of treating cancer by pretreatment with an anti-mitotic agent followed by an aurora kinase inhibitor. This application claims priority to US Provisional Patent Application Serial No. 60 / 953,087, filed July 31, 2007. Background technique [0002] Taxanes, such as paclitaxel and docetaxel, and vinca alkaloids, target the microtubules responsible for distributing replicating sister chromatids to each daughter cell. Disruption of microtubules inhibits cell division and leads to apoptosis. [0003] KSP inhibitors interfere with the function of mitokinetin, thus disrupting normal mitosis and blocking cell division. Mitokinin-KSP, called Eg5, is required for centrosome segregation. Cells in which KSP function is inhibited arrest in mitosis with unsegregated centrosomes (Blangy et al., Cell 1995, 83:1159-1169, Heald, R., Cell 2000, 102, 399). Mitotic arrest leads to growth inhibition of tumor cells (Kaiser et al., ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/06A61P35/00A61K31/337A61K31/4365A61K31/506A61K31/517A61K31/519
CPCA61K31/519A61K31/506A61K31/4365A61K31/337A61K31/517A61K45/06A61P35/00A61K2300/00
Inventor A·D·巴索-波卡罗
Owner SCHERING AG
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