公开(公告)号：US08715927B2

公开(公告)日：2014-05-06

申请号：US13131936

申请日：2009-04-22

申请人： R. Stephen Lloyd ,  Irina G. Minko ,  Amanda K. McCullough

发明人： R. Stephen Lloyd ,  Irina G. Minko ,  Amanda K. McCullough

IPC分类号： C12Q1/68 ,  C12Q1/48 ,  C12N9/10 ,  C07H21/00 ,  C07H21/04

CPC分类号： A61K45/06 ,  A61K31/195 ,  A61K31/56 ,  A61K31/70 ,  A61K33/24 ,  G01N2333/9126 ,  G01N2500/02 ,  A61K2300/00

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。

公开(公告)号：US20110236507A1

公开(公告)日：2011-09-29

申请号：US13131936

申请日：2009-04-22

申请人： R. Stephen Lloyd ,  Irina G. Minko ,  Amanda K. McCullough

发明人： R. Stephen Lloyd ,  Irina G. Minko ,  Amanda K. McCullough

IPC分类号： A61K33/24 ,  A61K31/198 ,  A61K31/675 ,  A61K31/255 ,  A61K31/407 ,  C12Q1/48 ,  C12Q1/68 ,  A61P35/00 ,  A61P31/00

CPC分类号： A61K45/06 ,  A61K31/195 ,  A61K31/56 ,  A61K31/70 ,  A61K33/24 ,  G01N2333/9126 ,  G01N2500/02 ,  A61K2300/00

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. Subjects in need of treatment with an ICL-inducing agent, include, for example, subjects diagnosed with a hyperproliferative disease, an autoimmune disease or an infectious disease. 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。 需要用ICL诱导剂治疗的受试者包括例如被诊断患有过度增殖性疾病，自身免疫性疾病或感染性疾病的受试者。 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。