Definition

An orally bioavailable inhibitor of the nuclear enzyme poly(ADP-ribose) polymerase (PARP), with potential chemo/radiosensitizing and antineoplastic activities. Upon administration, saruparib selectively targets and binds to PARP and prevents PARP-mediated DNA repair of single-strand DNA breaks via the base-excision repair pathway. This enhances the accumulation of DNA strand breaks and promotes genomic instability and eventually leads to apoptosis. This may enhance the cytotoxicity of DNA-damaging agents. PARP catalyzes post-translational ADP-ribosylation of nuclear proteins that signal and recruit other proteins to repair damaged DNA and is activated by single-strand DNA breaks. The PARP-mediated repair pathway is dysregulated in a variety of cancer cell types.