Inhibition of DNA polymerases to augment chemotherapeutic and antimicrobial agents
    4.
    发明授权
    Inhibition of DNA polymerases to augment chemotherapeutic and antimicrobial agents 失效
    抑制DNA聚合酶以增强化学治疗和抗微生物剂

    公开(公告)号:US08715927B2

    公开(公告)日:2014-05-06

    申请号:US13131936

    申请日:2009-04-22

    摘要: Disclosed herein is the identification of human DNA polymerase κ (pol κ) as the polymerase that mediates repair of DNA containing interstrand cros slinks (ICLs). The mechanism of action of a number of chemotherapeutic and antimicrobial agents is the induction of ICLs. Thus, provided herein is a method of enhancing the efficacy of a chemotherapeutic or antimicrobial agent in a subject, including selecting a subject in need of treatment with an ICL -inducing agent and administering to the subject an ICL-inducing agent and a therapeutically effective amount of an inhibitor of pol κ. Also provided is a composition for treating a hyperproliferative disease, an autoimmune disease or an infectious disease, comprising an ICL-inducing agent and an amount of an inhibitor of pol κ sufficient to enhance the efficacy of the ICL-inducing agent. Further provided is a method of identifying a DNA polymerase inhibitor.

    摘要翻译: 本文公开了人DNA聚合酶的鉴定; (pol&kgr))作为介导修复含有串联链的DNA(ICL)的聚合酶。 许多化学治疗和抗微生物剂的作用机制是ICL的诱导。 因此,本文提供的是提高受试者中化学治疗剂或抗微生物剂的功效的方法,包括选择需要用ICL诱导剂治疗的受试者,并向受试者施用ICL诱导剂和治疗有效量 的抑制剂。 还提供了用于治疗过度增殖性疾病,自身免疫性疾病或感染性疾病的组合物,其包含ICL诱导剂和一定量的抑制剂, 足以增强ICL诱导剂的功效。 进一步提供鉴定DNA聚合酶抑制剂的方法。