Poly(ADP-ribose) polymerases (PARPs) are involved in DNA repair following damage 
by endogenous or exogenous processes. It has become clear over the past decade 
that inhibition of PARP in the context of defects in other DNA repair mechanisms 
provide a tumor specific way to kill cancer cells. We describe the rationale for 
this approach and the design and discovery of niraparib, a potent PARP-1/2 
inhibitor with good cell based activity, selectivity for cancer over normal 
cells, and oral bioavailability. Niraparib was characterized in a number of 
preclinical models before moving to phase I clinical trials, where it showed 
excellent human pharmacokinetics suitable for once a day oral dosing, achieved 
its pharmacodynamic target for PARP inhibition, and had promising activity in 
cancer patients. It is currently being tested in phase 3 clinical trials as 
maintenance therapy in ovarian cancer and as a treatment for breast cancer.