PARP1
聚ADP核糖聚合酶
重新调整用途
聚合酶
DNA修复
PARP抑制剂
合成致死
癌症研究
药物重新定位
癌症
生物
药理学
生物化学
DNA
遗传学
酶
药品
生态学
作者
Nicola J. Curtin,Csaba Szabó
标识
DOI:10.1038/s41573-020-0076-6
摘要
The process of poly(ADP-ribosyl)ation and the major enzyme that catalyses this reaction, poly(ADP-ribose) polymerase 1 (PARP1), were discovered more than 50 years ago. Since then, advances in our understanding of the roles of PARP1 in cellular processes such as DNA repair, gene transcription and cell death have allowed the investigation of therapeutic PARP inhibition for a variety of diseases — particularly cancers in which defects in DNA repair pathways make tumour cells highly sensitive to the inhibition of PARP activity. Efforts to identify and evaluate potent PARP inhibitors have so far led to the regulatory approval of four PARP inhibitors for the treatment of several types of cancer, and PARP inhibitors have also shown therapeutic potential in treating non-oncological diseases. This Review provides a timeline of PARP biology and medicinal chemistry, summarizes the pathophysiological processes in which PARP plays a role and highlights key opportunities and challenges in the field, such as counteracting PARP inhibitor resistance during cancer therapy and repurposing PARP inhibitors for the treatment of non-oncological diseases. Several poly(ADP-ribose) polymerase (PARP) inhibitors have now been approved as treatments for various types of cancer. In this Review, Curtin and Szabo discuss the history of the development of PARP inhibitors and progress in their use for cancer therapy, as well as the potential for repurposing PARP inhibitors for the treatment of non-oncological diseases such as stroke.
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