Recent Advances in Structural Types and Medicinal Chemistry of PARP-1 Inhibitors

Poly (ADP-ribose) Polymerase-1 (PARP-1) is a member of 17 membered PARP family having diversified biological functions such as synthetic lethality, DNA repair, apoptosis, necrosis and histone binding, etc. The U.S. FDA has approved four PARP-1 inhibitors, namely Olaparib, Rucaparib, Niraparib, and Talazoparib. And, Veliparib has entered the late stage of clinical research as a PARP-1 inhibitor. At present, PARP-1 inhibitors have been approved for ovarian cancer, breast cancer, pancreatic cancer and other related indications. In recent years, more and more novel PARP-1 inhibitors have been reported. This review has attempted to summarize the structural types and characteristics of various novel PARP-1 inhibitors reported since 2020. And we outlined the current clinical application potential of PARP-1 inhibitors and further analyzed its current challenges and future development trends. Graphical abstract