Pommier Y
Laboratory of Molecular Pharmacology, National Cancer Institute, Bethesda, MD 20892-4255, USA.
Biochimie. 1998 Mar;80(3):255-70. doi: 10.1016/s0300-9084(98)80008-4.
The present review first describes the different type I topoisomerases found in eukaryotic cells: nuclear topoisomerase I (top1), topoisomerase 3 (top3), mitochondrial topoisomerase I and viral topoisomerases I. The second part of the review provides extensive information on the topoisomerase I inhibitors identified to date. These drugs can be grouped in two categories: top1 poisons and top1 suppressors. Both inhibit enzyme catalytic activity but top1 poisons trap the top1 catalytic intermediates ('cleavage complexes') while top1 suppressors prevent or reverse top1 cleavage complexes. The molecular interactions of camptothecin with the top1 cleavage complexes are discussed as well as the mechanisms of selective killing of cancer cells.
本综述首先描述了在真核细胞中发现的不同类型的I型拓扑异构酶：细胞核拓扑异构酶I（top1）、拓扑异构酶3（top3）、线粒体拓扑异构酶I和病毒拓扑异构酶I。综述的第二部分提供了迄今为止已鉴定的拓扑异构酶I抑制剂的广泛信息。这些药物可分为两类：top1毒药和top1抑制剂。两者都抑制酶的催化活性，但top1毒药会捕获top1催化中间体（“切割复合物”），而top1抑制剂则可预防或逆转top1切割复合物。文中还讨论了喜树碱与top1切割复合物的分子相互作用以及癌细胞选择性杀伤的机制。
