Ge Jun, Yin Yu, Li Yingpeng, Deng Yanru, Fu Hui
School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
Future Med Chem. 2022 Apr;14(7):511-525. doi: 10.4155/fmc-2021-0292. Epub 2022 Mar 8.
PARP1 is a hot target, and its inhibitors have been approved for cancer therapy. However, some undesirable properties restrict the application of PARP1 inhibitors, including drug resistance, side effects and low efficiency. For multifactorial diseases, dual-target drugs have exhibited excellent synergistic effects, such as reduced drug resistance, low side effects and high therapeutic efficacy, by simultaneously regulating the main pathogenic and compensatory signal pathways of diseases. In recent years, several dual-target inhibitors based on PARP1 have been reported and have demonstrated unique advantages. In this review we summarize the research progress in dual-target inhibitors based on PARP1 and discuss the related drug design strategies and structure-activity relationships. This work is expected to provide references for the development of PARP1 inhibitors.
聚（ADP - 核糖）聚合酶1（PARP1）是一个热门靶点，其抑制剂已被批准用于癌症治疗。然而，一些不良特性限制了PARP1抑制剂的应用，包括耐药性、副作用和低效率。对于多因素疾病，双靶点药物通过同时调节疾病的主要致病信号通路和代偿信号通路，表现出优异的协同效应，如降低耐药性、低副作用和高治疗效果。近年来，已经报道了几种基于PARP1的双靶点抑制剂，并显示出独特的优势。在这篇综述中，我们总结了基于PARP1的双靶点抑制剂的研究进展，并讨论了相关的药物设计策略和构效关系。这项工作有望为PARP1抑制剂的开发提供参考。
