选择性PARP-1抑制剂的研究进展  

Research Progress of Selective PARP-1 Inhibitors

作　　者：吴丹 霍晓丽 祝华建 邵加安 侯卫 张建康 WU Dan;HUO Xiaoli;ZHU Huajian;SHAO Jia’an;HOU Wei;ZHANG Jiankang(School of Pharmacy,Zhejiang University of Technology,Hangzhou 310014,China;School of Medicine,Zhejiang University City College,Hangzhou 310015,China)

机构地区：[1]浙江工业大学药学院,杭州310014 [2]浙大城市学院医学院,杭州310015

出　　处：《中国现代应用药学》2022年第20期2697-2706,共10页Chinese Journal of Modern Applied Pharmacy

摘　　要：聚腺苷二磷酸核糖聚合酶[Poly(ADP-ribose)polymerase,PARP]作为一种参与DNA修复的关键酶,已成为抗肿瘤药物开发的重要靶点。PARP抑制剂通过抑制DNA修复及协同致死作用可有效杀死肿瘤细胞,已被广泛应用于多种肿瘤的治疗。但大部分已被批准的PARP抑制剂因在抑制PARP-1的同时对PARP-2也有抑制作用而产生不良反应。因此,提高PARP-1抑制剂的选择性是解决这一问题的重要策略。本文综述已报道的选择性PARP-1抑制剂的研究进展,包括研究方法、构效关系、药理作用等。As a critical DNA-repair enzyme,poly(ADP-ribose)polymerase(PARP)has been validated as an important target for the development of anti-cancer drugs.PARP inhibitors could effectively kill cancer cells through inhibiting DNA repair and synergistic lethal effect,and have been widely used for the treatment of various cancers.However,most of the approved PARP inhibitors displayed severe side effects due to their poor selectivity for PARP-1 over PARP-2.Therefore,decreased side effects could be achieved by improving the selectivity for PARP-1.In this article,discussion on recent research progress including research methods,structure-activity relationships and pharmacological effects of reported selective PARP-1 inhibitors will be reviewed.

关 键 词：PARP-1 选择性抑制剂 抗肿瘤 构效关系 

分 类 号：R915[医药卫生—微生物与生化药学]