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公开(公告)号：US5705334A
公开(公告)日：1998-01-06
申请号：US328809
申请日：1994-10-25
申请人： Stephen J. Lippard , John M. Essigmann , Brian Donahue , Jeffrey H. Toney , Suzanne L. Bruhn , Pieter M. Pil , Steven J. Brown , Patti J. Kellett
发明人： Stephen J. Lippard , John M. Essigmann , Brian Donahue , Jeffrey H. Toney , Suzanne L. Bruhn , Pieter M. Pil , Steven J. Brown , Patti J. Kellett
CPC分类号： C07K14/435 , C07K14/43581 , C07K14/47 , C07K16/18 , C12Q1/68 , C12Q1/6876 , C12Q1/6883 , A61K38/00 , C12Q2600/142
摘要： Methods disclosed herein capitalize on the ability of DNA Structure Specific Recognition Proteins (SSRPs) to bind to genomic lesions formed by chemotherapeutic agents, particularly cisplatin-type agents. Methods are provided for predicting whether an agent that damages DNA will also be cytotoxic, and for predicting whether particular eukaryotic cells will be susceptible to killing by a genotoxic drug. A screening method is provided for identifying new genotoxic drugs that produce SSRP-recognized lesions in DNA. Methods also are provided for sensitizing particular eukaryotic cells to killing by chemotherapeutic agents, particularly cisplatin-type drugs.
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2.发明授权Nucleic acids encoding DNA structure-specific recognition protein and uses therefor 失效编码DNA结构特异性识别蛋白的核酸及其用途
公开(公告)号：US5359047A
公开(公告)日：1994-10-25
申请号：US814964
申请日：1991-12-26
申请人： Brian A. Donahue , Jeffrey H. Toney , John M. Essigmann , Stephen J. Lippard , Pieter M. Pil , Suzanne L. Bruhn , Steven J. Brown , Patti J. Kellett
发明人： Brian A. Donahue , Jeffrey H. Toney , John M. Essigmann , Stephen J. Lippard , Pieter M. Pil , Suzanne L. Bruhn , Steven J. Brown , Patti J. Kellett
IPC分类号： C12N15/09 , A61K38/00 , C07K14/39 , C07K14/435 , C07K14/47 , C07K16/00 , C07K16/18 , C12P21/02 , C12P21/08 , C12Q1/68 , C17N5/12
CPC分类号： C07K14/47 , C07K14/435 , C07K14/43581 , C07K16/18 , C12Q1/6876 , C12Q1/6883 , A61K38/00 , C12Q2600/142 , C12Q2600/158
摘要： DNA structure specific recognition protein of eukaryotic origin and DNA encoding such a factor, as well as probes specific for DNA structure specific recognition protein or DNA encoding it and methods of detecting DNA structure specific recognition protein in eukaryotic cells. In particular, a mammalian cellular factor that selectively recognizes and binds DNA damaged or modified by a drug (the anticancer drug, cis-diamminedichloroplatinum (II) or cisplatin) has been identified.
摘要翻译： 真核生物的DNA结构特异性识别蛋白和编码这样一个因子的DNA，以及DNA结构特异性识别蛋白或编码DNA的探针，以及检测真核细胞中DNA结构特异性识别蛋白的方法。 特别地，已经鉴定了选择性识别和结合被药物（抗癌药物，顺式二氨基二氯铂（II）或顺铂）损伤或修饰的DNA的哺乳动物细胞因子。
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公开(公告)号：US5670621A
公开(公告)日：1997-09-23
申请号：US258442
申请日：1994-06-09
申请人： Brian A. Donahue , Jeffrey H. Toney , John M. Essigmann , Stephen J. Lippard , Pieter M. Pil , Suzanne L. Bruhn , Steven J. Brown , Patti J. Kellett
发明人： Brian A. Donahue , Jeffrey H. Toney , John M. Essigmann , Stephen J. Lippard , Pieter M. Pil , Suzanne L. Bruhn , Steven J. Brown , Patti J. Kellett
IPC分类号： C12N15/09 , A61K38/00 , C07K14/39 , C07K14/435 , C07K14/47 , C07K16/00 , C07K16/18 , C12P21/02 , C12P21/08 , C12Q1/68 , C12N15/11
CPC分类号： C07K14/47 , C07K14/435 , C07K14/43581 , C07K16/18 , C12Q1/6876 , C12Q1/6883 , A61K38/00 , C12Q2600/142 , C12Q2600/158
摘要： DNA structure specific recognition protein of eukaryotic origin and DNA encoding such a factor, as well as probes specific for DNA structure specific recognition protein or DNA encoding it and methods of detecting DNA structure specific recognition protein in eukaryotic cells. In particular, a mammalian cellular factor that selectively recognizes and binds DNA damaged or modified by a drug (the anticancer drug, cis-diamminedichloroplatinum (II) or cisplatin) has been identified.
摘要翻译： 真核生物的DNA结构特异性识别蛋白和编码这样一个因子的DNA，以及DNA结构特异性识别蛋白或编码DNA的探针，以及检测真核细胞中DNA结构特异性识别蛋白的方法。 特别地，已经鉴定了选择性识别和结合被药物（抗癌药物，顺式二氨基二氯铂（II）或顺铂）损伤或修饰的DNA的哺乳动物细胞因子。
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公开(公告)号：US06475791B1
公开(公告)日：2002-11-05
申请号：US08866840
申请日：1997-06-02
申请人： Stephen J. Lippard , John M. Essigmann , Brian A. Donahue , Jeffrey H. Toney , Suzanne L. Bruhn , Pieter M. Pil , Steven J. Brown , Patti J. Kellett
发明人： Stephen J. Lippard , John M. Essigmann , Brian A. Donahue , Jeffrey H. Toney , Suzanne L. Bruhn , Pieter M. Pil , Steven J. Brown , Patti J. Kellett
IPC分类号： A61K4800
CPC分类号： C07K14/435 , A61K38/00 , C07K14/43581 , C07K14/47 , C07K16/18 , C12Q1/68 , C12Q1/6876 , C12Q1/6883 , C12Q2600/142
摘要： Methods disclosed herein capitalize on the ability of DNA Structure Specific Recognition Proteins (SSRPs) to bind to genomic lesions formed by chemotherapeutic agents, particularly cisplatin-type agents. Methods are provided for predicting whether an agent that damages DNA will also be cytotoxic, and for predicting whether particular eukaryotic cells will be susceptible to killing by a genotoxic drug. A screening method is provided for identifying new genotoxic drugs that produce SSRP-recognized lesions in DNA. Methods also are provided for sensitizing particular eukaryotic cells to killing by chemotherapeutic agents, particularly cisplatin-type drugs.
摘要翻译： 本文公开的方法利用DNA结构特异性识别蛋白（SSRP）结合由化学治疗剂，特别是顺铂型药剂形成的基因组病变的能力。 提供了用于预测损害DNA的药物是否也将是细胞毒性的方法，以及用于预测特定真核细胞是否易于被遗传毒性药物杀死的方法。 提供了一种筛选方法，用于鉴定在DNA中产生SSRP识别的病变的新基因毒性药物。 提供了用于使特定真核细胞对化学治疗剂，特别是顺铂类药物杀死的方法。
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公开(公告)号：US07169611B2
公开(公告)日：2007-01-30
申请号：US10299029
申请日：2002-11-18
CPC分类号： A61K47/64 , A61K47/55 , A61K47/554 , A61K47/557
摘要： The compositions and methods disclosed herein provide heterobifunctional programmable genotoxic compounds that can be designed to kill selected cells present in a heterogenous cell population. The present compounds comprise a first agent that inflicts damage on cellular DNA, and a second agent that attracts a macromolecular cell component such as a protein, which in turn shields genomic lesions from repair. Unrepaired lesions therefore persist in the cellular genome and contribute to the death of selected cells. In contrast, lesions formed in nonselected cells, which lack the cell component, are unshielded and thus are repaired. As a result, compounds described herein are less toxic to nonselected cells. Compounds of this invention can be designed to cause the selective killing of transformed cells, viral-infected cells and the like.
摘要翻译： 本文公开的组合物和方法提供异源双功能可编程遗传毒性化合物，其可被设计为杀死异源细胞群体中存在的所选细胞。 本发明化合物包含对细胞DNA造成损害的第一药剂和吸引大分子细胞成分例如蛋白质的第二药剂，其又将基因组病变屏蔽修复。 因此，未修复的病变在细胞基因组中持续存在，并有助于所选细胞的死亡。 相比之下，缺乏细胞成分的非选择细胞中形成的病变是非屏蔽的，因此被修复。 结果，本文所述的化合物对非选择性细胞的毒性较小。 本发明的化合物可被设计成引起转化细胞，病毒感染细胞等的选择性杀伤。
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公开(公告)号：US5512431A
公开(公告)日：1996-04-30
申请号：US268686
申请日：1994-06-29
IPC分类号： C12N15/09 , A61K31/7064 , C07H19/06 , C12Q1/68 , C12Q1/70
CPC分类号： A61K31/70 , A61K31/7064 , C07H19/06 , C12Q1/6897 , C12Q1/703
摘要： Methods and compositions related to HIV are disclosed. Using the methods of the present invention, nucleoside analogs may be screened for the ability to be incorporated by reverse transcriptase of human immunodeficiency virus ("HIV RT") and cause incorrect base pairing. Progressive mutation of the virus by such nucleoside analogs renders it non-viable.
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公开(公告)号：US07943600B2
公开(公告)日：2011-05-17
申请号：US11314186
申请日：2005-12-20
IPC分类号： A01N37/18 , A01N55/02 , A01N33/00 , A01N33/18 , A01N33/24 , A61K31/65 , A61K31/28 , A61K31/13 , A61K31/16 , A61K31/04 , A61K33/24 , C07C43/00 , C07C49/00 , C07C237/26
CPC分类号： A61K45/06 , A61K31/65 , A61K33/24 , Y02A50/471 , A61K2300/00
摘要： This invention provides methods and pharmaceutical compositions for treating a subject having a condition associated with an antibiotic resistant bacterial infection. The invention includes administering to a subject a therapeutically effective combination of an antibiotic and a toxic compound (e.g., a nucleic acid damaging agent, an alkylating agent, or a heavy metal containing compound).
摘要翻译： 本发明提供用于治疗具有与抗生素抗性细菌感染相关的病症的受试者的方法和药物组合物。 本发明包括向受试者施用抗生素和有毒化合物（例如核酸损伤剂，烷化剂或含重金属的化合物）的治疗有效组合。
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公开(公告)号：US5882941A
公开(公告)日：1999-03-16
申请号：US239428
申请日：1994-05-04
CPC分类号： A61K47/481 , A61K47/48023 , A61K47/48123 , A61K47/48146 , A61K47/48246
摘要： The compositions and methods disclosed herein provide heterobifunctional programmable genotoxic compounds that can be designed to kill selected cells present in a heterogenous cell population. The present compounds comprise a first agent that inflicts damage on cellular DNA, and a second agent that attracts a macromolecular cell component such as a protein, which in turn shields genomic lesions from repair. Unrepaired lesions therefore persist in the cellular genome and contribute to the death of selected cells. In contrast, lesions formed in nonselected cells, which lack the cell component, are unshielded and thus are repaired. As a result, compounds described herein are less toxic to nonselected cells. Compounds of this invention can be designed to cause the selective killing of transformed cells, viral-infected cells and the like.
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公开(公告)号：US20090062236A1
公开(公告)日：2009-03-05
申请号：US11699758
申请日：2007-01-29
IPC分类号： A61K31/675 , C12N5/00 , C12N5/02 , A61K31/175 , A61K31/131 , A61K31/28 , A61K31/10 , A61K31/53
CPC分类号： A61K47/64 , A61K47/54 , A61K47/55 , A61K47/554 , A61K47/557
摘要： The compositions and methods disclosed herein provide heterobifunctional programmable genotoxic compounds that can be designed to kill selected cells present in a heterogenous cell population. The present compounds comprise a first agent that inflicts damage on cellular DNA, and a second agent that attracts a macromolecular cell component such as a protein, which in turn shields genomic lesions from repair. Unrepaired lesions therefore persist in the cellular genome and contribute to the death of selected cells. In contrast, lesions formed in nonselected cells, which lack the cell component, are unshielded and thus are repaired. As a result, compounds described herein are less toxic to nonselected cells. Compounds of this invention can be designed to cause the selective killing of transformed cells, viral-infected cells and the like.
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公开(公告)号：US06500669B1
公开(公告)日：2002-12-31
申请号：US09103671
申请日：1998-06-23
IPC分类号： C12N1501
CPC分类号： A61K47/64 , A61K47/55 , A61K47/554 , A61K47/557
摘要： The compositions and methods disclosed herein provide heterobifunctional programmable genotoxic compounds that can be designed to kill selected cells present in a heterogenous cell population. The present compounds comprise a first agent that inflicts damage on cellular DNA, and a second agent that attracts a macromolecular cell component such as a protein, which in turn shields genomic lesions from repair. Unrepaired lesions therefore persist in the cellular genome and contribute to the death of selected cells. In contrast, lesions formed in nonselected cells, which lack the cell component, are unshielded and thus are repaired. As a result, compounds described herein are less toxic to nonselected cells. Compounds of this invention can be designed to cause the selective killing of transformed cells, viral-infected cells and the like.
摘要翻译： 本文公开的组合物和方法提供异源双功能可编程遗传毒性化合物，其可被设计为杀死异源细胞群体中存在的所选细胞。 本发明化合物包括对细胞DNA造成损害的第一药剂和吸引诸如蛋白质的大分子细胞成分的第二药剂，其继而对基因组病变进行修复。 因此，未修复的病变在细胞基因组中持续存在，并有助于所选细胞的死亡。 相比之下，缺乏细胞成分的非选择细胞中形成的病变是非屏蔽的，因此被修复。 结果，本文所述的化合物对非选择性细胞的毒性较小。 本发明的化合物可被设计成引起转化细胞，病毒感染细胞等的选择性杀伤。
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