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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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公开(公告)号：US5879917A
公开(公告)日：1999-03-09
申请号：US434664
申请日：1995-05-04
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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