ABT-888 (Veliparib)

Number of foci detected using laser confocal microscopy and fluorescent Fluor 647 anti-H2A.X-phosphorylated (Ser139) antibody. Double-stranded breaks (red) are clearly augmented in cells incubated with 500 nmol/l of ABT-888 and 500 nmol/l of AZD-2281 compared with PBS and 1% dimethyl sulfoxide controls. Image analysis was performed using ImageJ and the ‘analyze particle’ function.

Nuclear Medicine Communications, 2011, 32, 1046–1051. ABT-888 (Veliparib) purchased from Selleck

Logarithmic growth curves of human Burkitt lymphoma cells over 5 days with 500 nmol/l of ABT-888 and AZD-2281 in combination with 0 Gy (a), 4 Gy (b), 8 Gy (c), and 12 Gy (d) of external beam radiation. The maximal relative reduction was 65.5% of viable cells and occurred with AZD-2281 (500 nmol/l) on day 5. DMSO, dimethyl sulfoxide.

Nucl Med Commun, 2011, 32(11), 1046-51. ABT-888 (Veliparib) purchased from Selleck

Colorimetric poly(ADP-ribose) polymerase (PARP) activity assay showing the relative activity of the PARP-1 enzyme in Raji lymphocyte tumor cells. Results show a highly significant difference in PARP activity in the controls [PBS and dimethyl sulfoxide (DMSO)] compared with 24 h incubation with 500 nmol/l of ABT-888 and 500 nmol/l of AZD-2281. A significant increase in PARP enzyme activity is shown in DMSO-incubated cells compared with PBS control.* P < 0.05.

Nucl Med Commun, 2011, 32(11), 1046-51. ABT-888 (Veliparib) purchased from Selleck

PARP inhibitors sensitize OVCAR-8 cells to FdUrd but not 5-FU. A, OVCAR-8 cells were exposed to the indicated concentrations of FdUrd (left) or 5-FU (right) along with vehicle, 3 μmol/L ABT-888 or 300 nmol/L AZD2281 for 24 hours. Following washing, ABT-888 and AZD2281 were readded to the plates initially exposed to these agents, and cells were cultured in the continued presence of ABT-888 or AZD2281 for 8 days until colonies formed. B, OVCAR-8 cells were exposed continuously to the indicated agents for 8 days. C, left, OVCAR-8 cells treated as in (A) except that the indicated concentrations of ABT-888 were used. Data shown are a representative experiment from 3 independent replicates. n =3 +SD. C, right, synergy between FdUrd and ABT-888 was calculated from the data in (C, left) using the median effect method and assuming that the agents are mutually exclusive. Combination index values less than 1 indicate synergy.

Cancer Res, 2011, 71, 4944-4954. ABT-888 (Veliparib) purchased from Selleck

ABT-888 blocks recovery from FdUrd-induced cell-cycle arrest, enhances FdUrd-induced apoptosis, and maximally increases killing when present during and after FdUrd exposure. A, OVCAR-8 cells were incubated with vehicle, 3 μmol/L ABT-888, 25 μmol/L FdUrd, or 3 μmol/L ABT-888 and 25 μmol/L FdUrd for 24 hours. One set of cells was immediately stained with propidium iodide (0 hours). The remaining samples were washed, ABT-888 readded (to the samples initially exposed to ABT-888), and stained 24 and 48 hours later. B, cells were treated as in (A) and stained with Annexin V-FITC 24 and 48 hours after removal of FdUrd (with readdition of ABT-888 to samples initially exposed to ABT-888). Apoptosis was measured as the percentage of Annexin V-positive cells. C and D, OVCAR-8 cells were plated, treated with indicated concentrations of FdUrd and 3 μmol/L ABT-888 using the exposure schemes depicted in (C), and assayed for clonogenicity (D).

Cancer Res, 2011, 71, 4944-54. ABT-888 (Veliparib) purchased from Selleck

ABT-888 sensitizes multiple ovarian cancer cell lines but not normal cells to FdUrd. A, A2780, SKOV3ip, OVCAR-5, and OVCAR-3 ovarian cancer cells were treated with FdUrd for 24 hours in combination with vehicle or the indicated concentrations of ABT-888 for 24 hours. Following washing, ABT-888 was readded to samples initially exposed to ABT-888, and cells were cultured until colonies formed. Data shown are a representative experiment from 3 independent replicates. n=3+SD. B, OSEtsT/hTERT immortalized ovarian surface epithelial cells and WS1 human fibroblasts were treated with FdUrd with and without 3 μmol/L ABT-888. Cell viability was assessed via MTS assay. Data shown are the averages of 3 independent experiments. N=3+SEM.

Cancer Res, 2011, 71, 4944-54. ABT-888 (Veliparib) purchased from Selleck

ABT-888 sensitizes to FdUrd and temozolomide more effectively than to other chemotherapy agents. OVCAR-8 cells were treated with indicated concentrations of FdUrd, topotecan, melphalan, cisplatin, doxorubicin, gemcitabine, etoposide, and temozolomide in the presence or absence of 3 μmol/L ABT-888 for 24 hours. Following washing, ABT-888 was readded to samples initially exposed to ABT-888, and cells were cultured until colonies formed. Data shown are a representative experiment from 2 independent replicates. N=3+SD. Experiments with FdUrd, topotecan, melphalan, and temozolomide were independently replicated 3 times

Cancer Res, 2011.July, 71:4944-54. ABT-888 (Veliparib) purchased from Selleck

T47D breast cancer cells were pretreated with indicated concentrations of ABT-888

Dr.Zhang of Tianjin Medical University. ABT-888 (Veliparib) purchased from Selleck

in vivo suppression of PAR formation by the PARP inhibitor ABT-888 upon induction of DNA damage

David Schürmann from University of Basel. ABT-888 (Veliparib) purchased from Selleck

Caption:  451 Lu is a melanoma cell line with high PARP expression that is resistant to temozolomide.  Treatment with 25 µM ABT-888 greatly increased sensitivity to temozolomide compared to cells without ABT-888 treatment as measured by MTS assay.

Dr Steve Reuland from University of Colorado Denver. ABT-888 (Veliparib) purchased from Selleck

Effect of ABT-888 on the viability of endometrial cancer cell line Hec50 and Ishikawa and ovarian cancer cell line SKOV3,Caov3 and PA-1 was detected by WST-1 method after 3 days treatment.

Dr Xiangbing Meng of University of Iowa. ABT-888 (Veliparib) purchased from Selleck