Dual-target Inhibitors of PARP1 in Cancer Therapy: A Drug Discovery Perspective

Poly (ADP-ribose) polymerase 1 (PARP1), a key enzyme in DNA repair, has emerged as a promising anticancer druggable target. An increasing number of PARP1 inhibitors have been discovered to treat cancer, most notably those characterized by BRCA1/2 mutations. Although PARP1 inhibitors have achieved great clinical success, their cytotoxicity, development of drug resistance, and restriction of indication have weakened their clinical therapeutic effects. To address these issues, dual PARP1 inhibitors have been documented as a promising strategy. Here, we review recent progress in the development of dual PARP1 inhibitors, summarize the different designs of dual-target inhibitors, and introduce their antitumor pharmacology, shedding light on the discovery of dual PARP1 inhibitors for cancer treatment.