NCIt definition : An orally bioavailable central nervous system (CNS) penetrant and inhibitor of nuclear
enzyme poly(ADP-ribose) polymerase (PARP) 1, with potential antineoplastic activity.
Upon oral administration, palacaparib selectively binds to PARP1, thereby preventing
repair of damaged DNA via the base excision repair (BER) pathway. This agent enhances
the accumulation of DNA strand breaks and promotes genomic instability eventually
leading to apoptosis. Palacaparib may enhance the cytotoxicity of DNA-damaging agents
and reverse tumor cell chemo- and radioresistance. PARP1 catalyzes post-translational
ADP-ribosylation of nuclear proteins that signal and recruit other proteins to repair
damaged DNA and plays a key role in the repair of single strand DNA (ssDNA) breaks
and double-strand break (DSBs). Palacaparib is able to penetrate the blood-brain barrier
(BBB).;
Semantic type(s)