Definition

An orally bioavailable inhibitor of nuclear enzyme poly(ADP-ribose) polymerase (PARP) 1, with potential antineoplastic activity. Upon oral administration, PARP1 inhibitor HS-10502 selectively binds to and blocks the activity of 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. HS-10502 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).