Biological activity

Veliparib (ABT-888) is a potent inhibitor of PARP1 and PARP2 with Ki of 5.2 nM and 2.9 nM in cell-free assays, respectively. It is inactive to SIRT2. Phase 3.

In vitro

Veliparib (ABT-888) is a potential anti-cancer drug acting as a PARP inhibitor，which inhibits PARP1 and PARP2 with Ki of 5.2 nM and 2.9 nM in cell-free assays，respectively.ABT-888 reduces clonogenic survival and inhibits DNA repair in H460 cells. ABT-888 inhibits the PARP activity with EC50 of 2 nM in C41 cells.

In vivo

ABT-888 inhibits PARP in B16F10 and 9L xenograft models, thus enhancing the anticancer activity of temozolomide. The Combined with other cytotoxic agents, ABT-888 shows strong antitumor effect in MX-1 xenograft model. ABT-888 reduces intratumor PAR levels by more than 95% at a dose of 3 and 12.5 mg/kg according to the the size of tumors in A375 and Colo829 xenograft models.

Features

ABT-888 enhances the effectiveness of common cancer treatments, such as radiation therapy and alkylating agents.