Research Progress of PARP-1 Related Dual Target Inhibitors

Abstract

The treatment of cancer has always been based on surgery, radiotherapy and chemotherapy, but the cure rate of these methods is often very low and the side effects on patients are very serious. With the gradual understanding of cancer, targeted drug therapy has gradually attracted the attention of the scientific community. Initially, doctors used some single target inhibitors as targeted drugs for tumor treatment. However, with the increasing of single drug resistance and side effects, the problems of single drug resistance and side effects gradually emerge in clinical practice. Poly ADP-ribose polymerase-1 inhibitor (parp-1i) can inhibit DNA damage and repair in cells, so it is used as a kind of targeted drugs for tumor therapy. At a time when single target drugs are facing challenges, scientists have turned their attention to dual target inhibitors related to parp-1i with stronger effects. In this paper, we focus on the challenges faced by PARP-1 related single target inhibitors and the research progress of HDAC inhibitors or BRD4 inhibitors combined with PARP-1 inhibitors as double target inhibitors. It was found out that some new synthesized dual PARP/HDAC inhibitors and PARP/BRD4 inhibitors have shown great anticancer activities in vitro experiments, including compound I-8 and II-16 Therefore, this review confirmsthat PARP-related dual target inhibitors can be a promising approach to treat cancer cell.