Veliparib (dihydrochloride) | CAS:912445-05-7

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Name:Veliparib dihydrochloride; ABT-888 dihydrochloride
Cat. No. :CS-0077
CAS No. :912445-05-7
Formula:C13H18Cl2N4O
M. Wt. : 317.21
Solubility:DMSO: ≥ 3.2 mg/mL

Veliparib (dihydrochloride) is a potent inhibitor of PARP1 and PARP2 with Ki of 5.2 nM and 2.9 nM in cell-free assays, respectively.IC50 & Target: Ki: 5.2 nM (PARP1), 2.9 nM (PARP2)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]. 

Albert JM, et al. Inhibition of poly(ADP-ribose) polymerase enhances cell death and improves tumor growth delay in irradiated lung cancer models. Clin Cancer Res. 2007 May 15;13(10):3033-42. Penning TD, et al. Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer. J Med Chem. 2009 Jan 22;52(2):514-23. Robert J. Kinders, et al. Preclinical Modeling of a Phase 0 Clinical Trial: Qualification of a Pharmacodynamic Assay of Poly (ADP-Ribose) Polymerase in Tumor Biopsies of Mouse Xenografts. Clin Cancer Res. Author manuscript; available in PMC 2009 Nov 1. Donawho CK, et al. ABT-888, an orally active poly(ADP-ribose) polymerase inhibitor that potentiates DNA-damaging agents in preclinical tumor models. Clin Cancer Res. 2007 May 1;13(9):2728-37.