Medicinal Chemistry of PARP Inhibitors: Structural Insights and Mechanistic Implications for Oncology

ABSTRACT Around the world, cancer contributes to every sixth death, emphasizing its severity as a global health concern. One of the main causes of cancer's growth is destabilization of the genome, and poly ADP‐ribose polymerase (PARP) inhibitors are a type of specific therapy intended to prevent tumor‐causing cells from repairing single‐strand DNA damage. The process of creating inhibitors for PARP has marked a vital shift while treating cancer by focusing on the DNA repair mechanisms in cells having homologous recombination (HR) deficits and BRCA1/2 mutations. With therapy for ovarian, pancreatic, breast, and prostate cancers with abnormalities in HR repair, PARPi has been authorized. It was suggested that PARP‐1 be used as a potential cancer therapeutic target. Based on research findings from 2020 to 2025, this review analysis explores the latent of PARP inhibitors to be powerful cancer treatment drugs. It also discusses the fundamentals of PARP, including its structure, role in DNA repair, and the clinical studies that regulate PARPi.