Veliparib (dihydrochloride)

Veliparib (dihydrochloride) is a potent inhibitor of PARP1 and PARP2 with K_is of 5.2 nM and 2.9 nM in cell-free assays, respectively. IC50 & Target: Ki: 5.2 nM (PARP1), 2.9 nM (PARP2)^[1] In Vitro: Veliparib is inactive to SIRT2 (>5 μM)^[1]. Veliparib inhibits the PARP activity with EC₅₀ of 2 nM in C41 cells^[2]. Veliparib can decrease the PAR levels in both irradiated and nonirradiated H460 cells. Veliparib reduces clonogenic survival and inhibits DNA repair by PARP-1 inhibition in H460 cells. Veliparib increases apoptosis and autophagy in H460 cells when combination with radiation^[3]. Veliparib inhibits PARP activity in H1299, DU145 and 22RV1 cells and the inhibition is independent of p53 function. Veliparib (10 μM) suppresses the surviving fraction (SF) by 43% in the clonogenic H1299 cells. Veliparib shows effective radiosensitivity in oxic H1299 cells. Veliparib can attenuate the SF of hypoxic-irradiated cells including H1299, DU145 and 22RV1^[4]. In Vivo: The oral bioavailability of Veliparib is 56%-92% in mice, SD rats, beagle dogs, and cynomolgus monkeys after oral administration^[1]. Veliparib (25 mg/kg, i.p.) can improve tumor growth delay in a NCI-H460 xenograft model. Combination with radiation, veliparib decreases the tumor vessel formation^[3]. Veliparib 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 can be maintained over time^[4].