Department of Oncology, School of Medicine, University of Torino, 10124 Torino, Italy.
Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy.
Int J Mol Sci. 2021 Apr 19;22(8):4203. doi: 10.3390/ijms22084203.
Poly(ADP-ribose) polymerases (PARP) are proteins responsible for DNA damage detection and signal transduction. PARP inhibitors (PARPi) are able to interact with the binding site for PARP cofactor (NAD+) and trapping PARP on the DNA. In this way, they inhibit single-strand DNA damage repair. These drugs have been approved in recent years for the treatment of ovarian cancer. Although they share some similarities, from the point of view of the chemical structure and pharmacodynamic, pharmacokinetic properties, these drugs also have some substantial differences. These differences may underlie the different safety profiles and activity of PARPi.
聚(ADP-核糖)聚合酶(PARP)是负责检测 DNA 损伤和信号转导的蛋白质。PARP 抑制剂(PARPi)能够与 PARP 辅助因子(NAD+)的结合位点相互作用,并将 PARP 捕获在 DNA 上。通过这种方式,它们抑制单链 DNA 损伤修复。近年来,这些药物已被批准用于治疗卵巢癌。尽管它们在化学结构和药效学、药代动力学特性方面有一些相似之处,但从化学结构和药效学、药代动力学特性方面来看,这些药物也存在一些实质性的差异。这些差异可能是 PARPi 不同安全性特征和活性的基础。