School of Pharmacy, Sungkyunkwan [corrected] University, Suwon 440-746, Republic of Korea.
Bioorg Med Chem Lett. 2013 May 1;23(9):2642-6. doi: 10.1016/j.bmcl.2013.02.094. Epub 2013 Mar 1.
Poly(ADP-ribose)polymerase-1 (PARP-1) enzyme is involved in the repair of DNA damages made by certain anticancer agents. It is suggested that PARP-1 inhibitors potentiate the cytotoxic effects and circumvent the resistance of DNA-modifying anticancer agents such as cisplatin. In this study, we conducted virtual screening of Korea Chemical Bank database targeting PARP-1 and identified several potent PARP-1 inhibitors with submicromolar IC50 values (77-79 nM). We then examined the chemosensitization of cisplatin by pre-treatment of PARP-1 inhibitors in cisplatin-resistant human gastric cancer cells. Our results show that PARP-1 inhibitors suppress the formation of poly(ADP-ribose) and enhance the cytotoxicity of cisplatin.
聚（ADP-核糖）聚合酶 1（PARP-1）酶参与某些抗癌药物引起的 DNA 损伤修复。有研究表明，PARP-1 抑制剂可增强细胞毒性作用，并克服 DNA 修饰型抗癌药物（如顺铂）的耐药性。在这项研究中，我们针对 PARP-1 对韩国化学银行数据库进行了虚拟筛选，鉴定出几种具有亚微摩尔 IC50 值（77-79 nM）的强效 PARP-1 抑制剂。然后，我们在顺铂耐药的人胃癌细胞中通过 PARP-1 抑制剂预处理来检测顺铂的化疗增敏作用。结果表明，PARP-1 抑制剂抑制聚（ADP-核糖）的形成，并增强顺铂的细胞毒性。
