Definition

An orally bioavailable inhibitor of nuclear enzyme poly(ADP-ribose) polymerase (PARP) 1, with potential antineoplastic activity. Upon oral administration, PARP1 inhibitor GS-0201 selectively binds to and inhibits the activity of PARP1, thereby preventing the repair of damaged DNA via the base excision repair (BER) pathway. This enhances the accumulation of DNA strand breaks and promotes genomic instability eventually leading to apoptosis. 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 breaks (DSBs).