AG14361

AG14361 is a novel poly (ADP-ribose) polymerase-1 inhibitor with a GI50 of 10.9 µM. AG14361 enhances temozolomide activity in all MMR-proficient cells (1.5–3.3-fold) but is more effective in MMR-deficient cells (3.7–5.2-fold potentiation), overcoming temozolomide resistance. AG14361 significantly potentiated camptothecin-mediated cytotoxicity in all cells, except the base excision repair–deficient EM9 cells. In the breast cancer cell lines, AG14361 had no effect on IR-induced degradation of IkappaBalpha or nuclear translocation of p50 or p65. However, AG14361 inhibited IR-induced NF-kappaB-dependent transcription of a luciferase reporter gene.