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USE OF COMBINATION OF ANTI-ANGIOGENIC SUBSTANCE AND c-kit KINASE INHIBITOR

a technology of c-kit and anti-angiogenic substances, which is applied in the field of combination of antiangiogenic substances and c-kit kinase inhibitors, can solve the problems of not providing sufficient antitumor effect, and not being able or unable to obtain antitumor effects, and achieve excellent antitumor effects

Inactive Publication Date: 2009-02-26
EISIA R&D MANAGEMENT CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0011]In order to solve the above problem, the present inventors have gone through keen examination, as a result of which combined use of 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide and c-kit inhibitor imatinib was found to show an excellent antitumor effect.

Problems solved by technology

None of them, however, provides sufficient antitumor effect, and thus development of a novel antitumor drug has been strongly desired.
However, it has not been elucidated yet what kind of antitumor effect can or cannot be obtained with a pharmaceutical composition containing a combination of these substances.

Method used

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  • USE OF COMBINATION OF ANTI-ANGIOGENIC SUBSTANCE AND c-kit KINASE INHIBITOR

Examples

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example 1

Combinational Use of Compound of the Invention and c-Kit Inhibitor in Human Cancer Cell Line Subcutaneous Xenograft Model (In Vivo)

[0198]Human gastrointestinal stromal tumor cell line GIST882 (supplied by The Brigham and Women's Hospital, Inc.) was cultured in RPMI1640 (containing 10% FBS) in a 5% carbon dioxide incubator to about 80% confluence. Following cultivation, each cell was collected by trypsin-EDTA treatment according to a general method. Using a phosphate buffer containing 50% matrigel, 5×107 cells / mL suspension was prepared, and 0.2 mL each of the resulting cell suspension was subcutaneously transplanted into the flank of a nude mouse. Starting from twenty-one days after the transplantation, 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide (10 mg / kg or 30 mg / kg, once a day, for two weeks) and imatinib (160 mg / kg, twice a day, for two weeks) were orally administered alone or in combination. 4-(3-chloro-4-(cyclopropylaminocarbonyl)amin...

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Abstract

The object of the present invention is to find a pharmaceutical composition and a method for treating cancer that show an excellent antitumor effect. Combinational use of 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide and analogues thereof can result in an excellent antitumor effect when combined with a substance having a c-kit kinase-inhibiting activity.

Description

FIELD OF THE INVENTION[0001]The present invention relates to a pharmaceutical composition and a kit comprising a combination of a compound represented by Formula (I), a pharmacologically acceptable salt thereof or a solvate thereof (hereinafter, also referred to as a “compound of the invention”) and a substance having a c-kit kinase-inhibiting activity (hereinafter, also referred to as a “c-kit inhibitor”), to a method for treating cancer comprising administering an effective amount of the pharmaceutical composition to a patient, to use of the compound of the invention for producing the pharmaceutical composition, and to the compound of the invention used for the pharmaceutical composition.BACKGROUND OF THE INVENTION[0002]Examples of conventionally used chemotherapeutic agents for cancer include alkylating agents such as cyclophosphamide, antimetabolites such as methotrexate and fluorouracil, antibiotics such as adriamycin, mitomycin and bleomycin, plant-derived taxol, vincristine a...

Claims

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Application Information

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IPC IPC(8): A61K39/395C07D215/233A61K31/47A61K31/506
CPCA61K31/404A61K31/4409A61K31/4439A61K31/47A61K31/4709C07D215/48A61K31/506A61K31/517A61K31/519A61K31/5377A61K45/06A61K31/502A61P35/00A61P43/00
Inventor YAMAMOTO, YUJI
Owner EISIA R&D MANAGEMENT CO LTD
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