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Combination of checkponit kinase ( CHK) and telangiectasia mutated (ATM) inhibitors for the treatment of cancer

A telangiectasia and inhibitor technology, which can be used in drug combinations, medical preparations containing active ingredients, active ingredients of heterocyclic compounds, etc., and can solve problems such as downstream event defects

Inactive Publication Date: 2010-09-08
ASTRAZENECA AB
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Indeed, p53-mediated downstream events are also defective after IR exposure in A-T cells

Method used

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  • Combination of checkponit kinase ( CHK) and telangiectasia mutated (ATM) inhibitors for the treatment of cancer
  • Combination of checkponit kinase ( CHK) and telangiectasia mutated (ATM) inhibitors for the treatment of cancer
  • Combination of checkponit kinase ( CHK) and telangiectasia mutated (ATM) inhibitors for the treatment of cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment

[0148] CHK-ATM combination

[0149] Using the cell viability endpoint, a combinatorial experiment was performed to evaluate the effect of the CHK inhibitor 5-(3-fluoro-phenyl)-3-ureido-thiophene-2-carboxylic acid (S)-piperidin-3-ylamide on the ATM inhibitor 2-[(2,6)-2,6-dimethylmorpholin-4-yl]-N-[5-(6-morpholin-4-yl-4-oxo-4H-pyridine pyran-2-yl)-9H-thioxanth-2-yl]acetamide sensitive ability.

[0150] When using a single drug, select cell lines that are relatively insensitive to each compound. Specifically, two cell lines with blunt p53 that had previously been shown to be more sensitive to CHK inhibition than cells expressing wild-type p53 were used. The effect of simultaneous compound addition and exposure was examined and compared to the effect of sequential compound addition followed by simultaneous exposure.

[0151] The cell lines used in this study were SW620 endogenously expressing mutant p53, and NCI-H460dnp53 stably transfected to express dominant negative p53. ...

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Abstract

A combination, comprising a checkpoint kinase (CHK) inhibitor, or a pharmaceutically acceptable salt thereof, and an ataxia telangiectasia mutated (ATM) inhibitor, or a pharmaceutically acceptable salt thereof is described.

Description

technical field [0001] The present invention discloses therapies for the treatment of cancer. Background of the invention [0002] Chemotherapy and radiation irradiation are currently the main options for treating cancer, but their therapeutic applicability is severely limited due to their strong adverse effects on normal tissues and the frequent emergence of drug resistance in tumor cells. There is therefore a great need to improve the efficacy of treating cancer without increasing its toxicity. In some cases, one way to improve efficacy is to use anticancer agents in combination, where the combination produces a better therapeutic effect than either drug alone. [0003] Combination regimens will make more therapies available to patients with cancer. For example, in one possible scenario, the drug could increase the sensitivity of malignant cells to other drugs in the combination therapy. In other cases, the combination of anticancer agents may have additive or even syne...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/40A61K31/41A61K31/435A61K31/495A61K31/5377A61K31/55A61P35/00
CPCA61K45/06A61K31/41A61K31/495A61K31/5377A61K31/55A61K31/40A61K31/435A61P35/00A61P35/02A61P35/04A61P43/00A61K2300/00
Inventor G·C·M·史密斯S·扎布卢多夫
Owner ASTRAZENECA AB
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