Recent Progress in Poly(ADP–Ribose) Polymerase‐1 Inhibitors for Application in Cancer

Abstract An ADP‐ribosylating enzyme called poly (ADP–ribose) polymerase 1 (PARP1) is necessary to start several types of DNA repair. PARP1 also contributes significantly to the regulation of gene expression through enzyme‐independent motif recognition and enzyme‐dependent chromatin remodeling. Thus, synthetic lethality is achieved in the therapy of tumors and cancers by blocking undesired DNA repair by the inhibition of its enzyme activity with small molecules. In addition to outlining the most recent research from 2019 to 2024 on the precise ways in which PARP1 regulates each process independently, we discussed how transcription and DNA repair are interdependent enough that perturbations caused by PARP1 enzymatic inhibition, disease‐related enzyme hyperactivation. Herein, this concept review systematically summarizes the different approach for designing selective PARP1 inhibitor that are i) PARP1–DNA trapping approach, ii) hybrid approach, iii) PROTAC approach, and iv) dual target inhibitor approach and updates on clinical trials.