Veliparib (ABT-888)

InformationVeliparib (ABT-888, NSC 737664) is a potent inhibitor ofPARP1andPARP2withKiof 5.2 nM and 2.9 nM in cell-free assays, respectively. It is inactive to SIRT2. Veliparib increasesautophagyandapoptosis. Phase 3.In vitroABT-888 is inactive to SIRT2 (>5 μM). ABT-888 inhibits the PARP activity with EC50 of 2 nM in C41 cells. ABT-888 could decrease the PAR levels in both irradiated and nonirradiated H460 cells. ABT-888 also reduces clonogenic survival and inhibits DNA repair by PARP-1 inhibition in H460 cells. ABT-888 increases apoptosis and autophagy in H460 cells when combination with radiation. ABT-888 also inhibits PARP activity in H1299, DU145 and 22RV1 cells and the inhibition is independent of p53 function. ABT-888 (10 μM) suppresses the surviving fraction (SF) by 43% in the clonogenic H1299 cells. ABT-888 shows effective radiosensitivity in oxic H1299 cells. Furthermore, ABT-888 could attenuate the SF of hypoxic-irradiated cells including H1299, DU145 and 22RV1.In vivoThe oral bioavailability of ABT-888 is 56%-92% in mice, Sprague-Dawley rats, beagle dogs, and cynomolgus monkeys after oral administration. ABT-888 (25 mg/kg i.p.) could improve tumor growth delay in a NCI-H460 xenograft model with well tolerated. Combination with radiation, ABT-888 decreases the tumor vessel formation. ABT-888 reduces intratumor PAR levels by more than 95% at a dose of 3 and 12.5 mg/kg in A375 and Colo829 xenograft models and the suppression could be maintained over time.Cell Datacell lines：ConA-stimulated T cells and LPS-stimulated B cellsConcentrations：Incubation Time：Powder Purity:≥99%. Specification: 10mM in DMSO Molecular Formula: C13H16N4O Molecular Weight: 244.29