Assays for agents with selective cytotoxicty to hdac...

G - Physics – 01 – N

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G01N 33/50 (2006.01)

Patent

CA 2596405

This invention relates to a method of identifying and/or obtaining an agent which is selectively cytotoxic to histone deacetylase inhibitor (HDACi) resistant cells, said method comprising the steps of: a) incubating HDACi resistant cells and HDACi sensitive cells with a test agent, b) determining the cytotoxicity of the test agent for said HDACi resistant cells and the cytotoxicity of the test agent for said HDACi sensitive cells, wherein an increase in cytoxicity of the test agent for said HDACi resistant cells relative to said HDACi sensitive cells is indicative that the test agent is an agent which is selectively cytotoxic to HDACi resistant cells. The invention is based on the recognition that cells which are resistant to inhibitors of histone deacetylases (HDACis) such as PXD101 are hypersensitized to certain anti-cancer agents.

La présente invention concerne un procédé d'identification et/ou d'obtention d'un agent sélectivement cytotoxique envers les cellules résistantes à l'inhibiteur de l'histone désacétylase (HDACi), ledit procédé comprenant les étapes consistant à: a) incuber des cellules résistantes à l'HDACi et des cellules sensibles à l'HDACi avec un agent à tester, b) déterminer la cytotoxicité de l'agent à tester vis-à-vis desdites cellules résistantes à l'HDACi et la cytotoxicité de l'agent à tester vis-à-vis desdites cellules sensibles à l'HDACi, une augmentation de la cytotoxicité de l'agent à tester vis-à-vis desdites cellules résistantes à l'HDACi par rapport auxdites cellules sensibles à l'HDACi indiquant que l'agent à tester est un agent sélectivement cytotoxique envers les cellules résistantes à l'HDACi. L'invention est basée sur l'acceptation du fait que les cellules qui sont résistantes aux inhibiteurs des histones désacétylases (HDACi) tels que PXD101, sont hypersensibilisées à certains agents anticancéreux.

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