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Assays for agents with selective cytotoxicty to HDAC resistant cell lines

机译:对HDAC耐药细胞系具有选择性细胞毒性的试剂测定

摘要

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.
机译:本发明涉及一种鉴定和/或获得对组蛋白脱乙酰基酶抑制剂(HDACi)抗性细胞有选择性细胞毒性的试剂的方法,所述方法包括以下步骤:a)将HDACi抗性细胞和HDACi敏感细胞与测试试剂一起温育, b)确定测试试剂对所述HDACi耐药细胞的细胞毒性和测试试剂对所述HDACi敏感细胞的细胞毒性,其中相对于所述HDACi敏感细胞,所述HDACi耐药细胞的测试药物的细胞毒性增加表明测试试剂是对HDACi抗性细胞有选择性细胞毒性的试剂。本发明基于以下认识:对组蛋白脱乙酰基酶(HDACis)的抑制剂例如PXD101具有抗性的细胞对某些抗癌剂超敏。

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