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ASSAYS FOR AGENTS WITH SELECTIVE CYTOTOXICTY TO HDAC RESISTANT CELL LINES

机译:对HDAC抗性细胞株具有选择性细胞毒作用的代理商的检测

摘要

This invention relates to a method of identifying and/or obtaining an agentwhich is selectively cytotoxic to histone deacetylase inhibitor (HDACi)resistant cells, said method comprising the steps of: a) incubating HDACiresistant cells and HDACi sensitive cells with a test agent, b) determiningthe cytotoxicity of the test agent for said HDACi resistant cells and thecytotoxicity of the test agent for said HDACi sensitive cells, wherein anincrease in cytoxicity of the test agent for said HDACi resistant cellsrelative to said HDACi sensitive cells is indicative that the test agent is anagent which is selectively cytotoxic to HDACi resistant cells. The inventionis based on the recognition that cells which are resistant to inhibitors ofhistone deacetylases (HDACis) such as PXD101 are hypersensitized to certainanti-cancer agents.
机译:本发明涉及一种识别和/或获得代理的方法对组蛋白脱乙酰基酶抑制剂(HDACi)有选择性的细胞毒性抗性细胞,所述方法包括以下步骤:a)孵育HDACi抗性细胞和HDACi敏感细胞与测试剂的结合,b)确定测试剂对所述HDACi耐药细胞的细胞毒性和测试剂对所述HDACi敏感细胞的细胞毒性,其中所述HDACi耐药细胞的测试剂细胞毒性增加相对于所述HDACi敏感细胞而言,指示测试试剂是对HDACi耐药细胞具有选择性细胞毒性的药物。本发明基于这样的认识,即细胞对组蛋白脱乙酰基酶(HDACis),例如PXD101对某些蛋白过敏抗癌药。

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