Veliparib (ABT-888)是一种有效的PARP1和PARP2抑制剂，无细胞试验中Ki分别为5.2 nM和2.9 nM，对SIRT2没有活性。

98% min

Store at -20℃ for one year（Powder）；Store at 2-4℃ for two weeks；Store at -20℃ for six months after dissolution.

ABT-888; ABT 888; ABT888; NSC 737664

DMSO Solubility: 17 mg/mL (69.58 mM)

PARP2 ,PARP1

ABT-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.

The 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.

[1] Donawho CK, et al, Clin Cancer Res, 2007, 13 (9), 2728-2737.

[2] Penning TD, et al, J Med Chem, 2009, 52(2), 514-523.

[3] Albert JM, et al, Clin Cancer Res, 2007, 13(10), 3033-3042.