PARP-1抑制剂的研究进展

Recent advances on the research of PARP-1 inhibitors

聚腺苷二磷酸核糖聚合酶-1(poly(ADP-ribose)polymerase-1,PARP-1)能够催化ADP-核糖单元从烟酰胺腺嘌呤二核苷酸(nicotinamide adenine dinucleotide,NAD+)转移至受体蛋白,参与单链受损DNA的修复,是一种全新机制的抗癌药物靶点.目前多个PARP-1抑制剂处于临床试验阶段,PARP-1抑制剂不仅可以作为化疗和放疗的增敏剂,而且可以单独使用,用于治疗乳腺癌易感基因(BRCA1/2)缺陷性肿瘤.本文综述了6种结构类型PARP-1抑制剂的构效关系,并总结了代表性小分子抑制剂与PARP-1的结合模式.

Poly（ADP-ribose）polymerase-1 （PARP-1） plays significant roles in the DNA repair process by catalyzing the transfer of ADP-ribose from NAD＋ to its receptors. It is a promising anticancer drug target and many PARP-1 inhibitors have been developed and used in the clinical trials. PARP-1 inhibitors could be used not only as chemo/ radiotherapy sensitizers, but also as single agents to selectively kill BRCA deficient cancer cells. In this review, 6 classes of PARP-1 inhibitors with distinct structure scaffold were described in terms of the structure-activity relationships and their binding modes within the catalytic domain of PARP-1.