PARP-1抑制剂研究进展

Progress in the study of PARP-1 inhibitors

聚腺苷二磷酸核糖聚合酶-1(PARP-1)是存在于真核细胞中具有显著生物活性的核酶。在动物模型中,该酶的抑制剂为多形式的再灌注损伤、炎症和神经毒性引起的组织伤害提供了重要的保护作用。因此,用药物抑制该酶能够用于炎症、神经退行性疾病以及与该酶激活有关的其他疾病的治疗。基于该酶结构的药物设计是创新药物研究的重要策略。本文简要介绍PARP-1作为治疗靶点的基本原理,并综述基于不同结构骨架的PARP-1类抑制剂的合成研究进展。

The poly（ADP-ribose）polymerase-1 （PARP-1） is a nuclear enzyme presented in eukaryotic cells with significant biological activity. PARP-1 inhibitors provided remarkable protection from tissue damage in various forms of reperfusion injury, inflammation, and neurotoxicity in animal models. Thus, inhibition of PARP-1 by pharmacological agents could be useful in the treatment of inflammatory disease, neurodegenerative disease, and several other diseases involved in PARP-1 activation. Structure based drug design of PARP has become an important strategy of drug discovery. This review briefly introduces the basic principle of PARP-1 as therapeutic targets, and to provide an update on the progress of PARP-1 inhibitors based on different structure skeletons.