PARP-1/2 inhibitor ABT-767

An orally available inhibitor of the nuclear enzymes poly(ADP-ribose) polymerase (PARP) 1 and 2, with potential antineoplastic activity. Upon administration, ABT-767 selectively binds to PARP 1 and 2, 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. ABT-767 may enhance the cytotoxicity of DNA-damaging agents and reverse tumor cell chemo- and radioresistance. PARP catalyzes post-translational ADP-ribosylation of nuclear proteins that signal and recruit other proteins to repair damaged DNA and can be activated by single strand DNA (ssDNA) breaks.