PARP inhibition

Poly [ADP-ribose] polymerases (PARPs) are a group of proteins known to be involved in the repair of single-strand breaks in DNA.¹

A healthy cell’s DNA undergoes damage every day, with approximately 10,000 spontaneous single-strand breaks that require repair.¹

Inhibition of PARP1 with palacaparib (AZD9574) leads to the trapping of PARP1 bound to DNA single-strand breaks, stalling of replication forks, their collapse and the generation of DNA double-strand breaks and cancer cell death. In tumor cells that already have compromised DNA repair mechanisms (such as loss of BRCA1 or BRCA2 function, affecting double-strand break repair), inhibition of PARP1 leads to excessive accumulation of DNA damage and may cause death of the cell.^1,2