The effort to identify PARP1 selective inhibitor led to the first discovery of 2-[1-(4,4-Difluorocyclohexyl)piperidin-4-yl]−6-fluoro-3-oxo-2,3-dihydro-1H-isoindole-4-carboxamide (NMS-P118): A potent, orally available, and highly selective PARP1i with excellent absorption, distribution, metabolism, and excretion (ADME) and pharmacokinetic (PK) profile showing high efficacy in breast cancer and pancreatic cancer xenograft models [95]. Here, PARP1 is linked to familial pancreatic carcinoma.