PARP抑制剂的作用机制和研究进展

Progress in the research of PARP inhibitors and their mechanisms of action

在碱基切除修复途径中,聚腺苷二磷酸核糖聚合酶[poly(ADP-ribose)polymerase,PARP]是一种关键的DNA修复酶。PARP具有DNA损伤应答、调控细胞凋亡、维持基因组稳定等作用。PARP抑制剂通过影响PARP功能从而阻碍DNA修复过程,使同源重组修复缺失的细胞死亡。近年来,PARP作为抗肿瘤治疗的热门靶点得到广泛研究。目前,olaparib是首个作为PARP抑制剂成功上市的药物,rucaparib和niraparib也将相继上市。本文针对PARP-1及PARP-1抑制剂的作用机制和活性较好的几类PARP抑制剂结构进行阐述,对目前处于临床的PARP抑制剂研究进展做一介绍并展望PARP抑制剂发展前景和需要解决的问题。

Poly（ADP-ribose） polymerase（PARP） acts as essential DNA repair enzyme in the base excision repair pathway. PARP involves in many cellular processes including DNA damage response,maintaining the integrity of the genome and apoptosis regulation. PARP inhibitors inhibit PARP activity that selectively kills cancer cells by targeting homologous recombination repair defects. In recent years,the research on PARP inhibitors has become the hot target in cancer therapy. Olaparib,a PARP inhibitor,is the first drug that has been come to market so far,two drugs rucaparib and niraparib have been approved. In this paper,based on the structure and mechanism of PARP-1,the major structure types and recent progress of PARP-1 inhibitors were reviewed. This paper also introduced current clinical PARP inhibitors and looked forward to the development prospect of PARP inhibitors and the problems to be solved.