ABT-888 is a potent inhibitor of both PARP-1 and PARP-2 by [3H]NAD+ with Kis of 5.2 and 2.9 nmol/L, respectively.The compound has good oral bioavailability and crosses the blood-brain barrier. ABT-888 strongly potentiated temozolomide in the B16F10 s.c. murine melanoma model. In the MX-1 breast xenograft model(BRCA1 deletion and BRCA2 mutation), ABT-888 potentiated cisplatin, carboplatin, and cyclophosphamide,causing regression of established tumors, whereas with comparable doses of cytotoxic agents alone, only modest tumor inhibition was exhibited[1]. A significant correlation exists between MRE11 expression levels and cytotoxicity to ABT-888 at 10 µM (R2=0.915, P<0.001). ABT-888 was toxic to both oxic and hypoxic cells. When ABT-888 was combined with ionizing radiation (IR), clonogenic radiation survival was decreased by 40-50% under oxic conditions. Under acute hypoxia, ABT-888 radiosensitized malignant cells to a level similar to oxic radiosensitivity.
ABT-888 is a potent inhibitor of both PARP-1 and PARP-2 by [3H]NAD+ with Kis of 5.2 and 2.9 nmol/L, respectively.The compound has good oral bioavailability and crosses the blood-brain barrier. ABT-888 strongly potentiated temozolomide in the B16F10 s.c. murine melanoma model. In the MX-1 breast xenograft model(BRCA1 deletion and BRCA2 mutation), ABT-888 potentiated cisplatin, carboplatin, and cyclophosphamide,causing regression of established tumors, whereas with comparable doses of cytotoxic agents alone, only modest tumor inhibition was exhibited[1]. A significant correlation exists between MRE11 expression levels and cytotoxicity to ABT-888 at 10 µM (R2=0.915, P<0.001). ABT-888 was toxic to both oxic and hypoxic cells. When ABT-888 was combined with ionizing radiation (IR), clonogenic radiation survival was decreased by 40-50% under oxic conditions. Under acute hypoxia, ABT-888 radiosensitized malignant cells to a level similar to oxic radiosensitivity.
