Veliparib

SKU: orb1305291

Description

Veliparib

Research Area

Cell Biology, Epigenetics & Chromatin, Molecular Biology

Key Properties

• CAS Number: 912444-00-9
• MW: 244.29
• Purity: 98.66%
• Formula: C₁₃H₁₆N₄O
• SMILES: C(N)(=O)C1=C2C(N=C(N2)[C@@]3(C)CCCN3)=CC=C1
• Target: PARP,Autophagy
• Solubility: Ethanol:< 1 mg/mL (insoluble or slightly soluble);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (8.19 mM);DMSO:50 mg/mL (204.67 mM);H2O:< 1 mg/mL (insoluble or slightly soluble)

Bioactivity

• Target IC50:
  PARP2:2.9 nM (cell free)|PARP1:5.2 nM (cell free)
• In Vivo:
  PARP inhibition dramatically increased the efficacy of temozolomide at Veliparib doses as low as 3.1 mg/kg/d and a maximal efficacy achieved at 25 mg/kg/d. In the MX-1 breast xenograft model (BRCA1 deletion and BRCA2 mutation), Veliparib potentiated cisplatin, carboplatin, and cyclophosphamide, causing regression of established tumors, whereas, with comparable doses of cytotoxic agents alone, only modest tumor inhibition was exhibited . Veliparib increased tumor growth delay at well-tolerated doses in murine models. For a 5-fold increase in tumor volume, tumor growth delay was 1 day for Veliparib alone, 7 days for radiation alone, and 13.5 days for combination treatment. A decrease in vitro endothelial tubule formation with Veliparib/radiation combination treatment and von Willebrand factor staining of tumor sections revealed decreased vessel formation in vivo .
• In Vitro:
  Veliparib (ABT-888) is a potent inhibitor of both PARP-1 and PARP-2 with K(i)s of 5.2 and 2.9 nmol/L, respectively . In the HaCaT cell model, ABT-888 can reduce SM-induced NAD(+)/ATP depletion and apoptosis/necrosis . ABT-888 reduced clonogenic survival in H460 lung cancer cells and inhibited DNA repair as shown by enhanced expression of DNA strand break marker histone gamma-H2AX .
• Cell Research:
  Cell viability was quantified using the Cell Counting Kit-8 (CCK-8). This assay is based on Dojindo's highly water-soluble tetrazolium salt. WST-8 is reduced by dehydrogenases in cells to give an orange, water-soluble formazan dye. The amount of formazan dye generated by dehydrogenases in cells is directly proportional to the number of living cells. Briefly, exponentially growing HaCaT cells were seeded in 96-well plates at a density of 10,000 cells/well. 6 h or 24 h after exposure to SM and the administration of ABT-888, the CCK-8 reagent was added as recommended by the supplier .
• Animal Research:
  For oral pharmacokinetic studies, ABT-888 was separated from plasma and brain homogenate using liquid-liquid extraction with a mixture of ethyl acetate and hexane at alkaline pH. ABT-888 and the internal standard were separated from each other and coextracted contaminants on a 50 × 3 mm Keystone Betasil Cyano 5 μm C18 column with acetonitrile: 0.1% trifluoroacetic acid mobile phase (40:60, by volume) at a flow rate of 0.3 mL/min. Analysis was done on a Sciex API3000 Biomolecular Mass Analyzer with a turbo-ionspray interface using Sciex MacQuan software. The analysis of plasma pharmacokinetics from osmotic minipump (OMP) studies was conducted using acidified methanol precipitated plasma. Samples were injected onto a Phenomenex Synergi 4μ Polar RP column and ABT-888 eluted with a mixture of acetonitrile and 0.1% acetic acid in water at a flow rate of 0.4 mL/min. Mass analysis was done with a ThermoFinnigan LCQ Duo using Xcalibur software .

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Veliparib, poly ADP ribose polymerase, Autophagy, ABT 888, ABT-888, ABT888, inhibit, NSC 737664, PARP2, PARP1, PARP, NSC737664, NSC-737664, Inhibitor

Compound Identifiers

PubChem CID

11960529