Veliparib; ABT-888; NSC 737664 [T2591][CAS no. 912444-00-9]_TargetMol - 코아사이언스

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Veliparib

=ABT-888; NSC 737664

Cat.# T2591 / Size: 5mg, 10mg, 25mg, 50mg, 100mg

Veliparib (ABT-888) is an orally bioavailable inhibitor of PARP (Kis: 5.2/2.9 nM for PARP1/2). It enhances apoptosis and autophagy.

All products from TargetMol are for Research Use Only. Not for Human or Veterinary or Therapeutic Use.

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Biological Description 

Description	Veliparib (ABT-888) is an orally bioavailable inhibitor of PARP (Kis: 5.2/2.9 nM for PARP1/2). It enhances apoptosis and autophagy.
Targets&IC50	PARP2:2.9 nM (cell free), PARP1:5.2 nM (cell free)
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 [1]. In the HaCaT cell model, ABT-888 can reduce SM-induced NAD(+)/ATP depletion and apoptosis/necrosis [2]. 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 [3].
In vivo	PARP inhibition dramatically increased the efficacy of temozolomide at ABT-888 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), ABT-888 potentiated cisplatin, carboplatin, and cyclophosphamide, causing regression of established tumors, whereas, with comparable doses of cytotoxic agents alone, only modest tumor inhibition was exhibited [1]. ABT-888 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 ABT-888 alone, 7 days for radiation alone, and 13.5 days for combination treatment. A decrease in vitro endothelial tubule formation with ABT-888/radiation combination treatment and von Willebrand factor staining of tumor sections revealed decreased vessel formation in vivo [3].
Kinase Assay	PARP assays were conducted in a buffer containing 50 mmol/L Tris (pH 8.0), 1 mmol/L DTT, 1.5 μmol/L [3H]NAD+ (1.6 μCi/mmol), 200 nmol/L biotinylated histone H1, 200 nmol/L slDNA, and 1 nmol/L PARP-1 or 4 nmol/L PARP-2 enzyme. Reactions were terminated with 1.5 mmol/L benzamide, transferred to streptavidin Flash plates, and counted using a TopCount microplate scintillation counter [1].
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 [2].
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 [1].

Chemical Properties 

Synonyms	ABT-888, NSC 737664
Molecular Weight	244.298
Formula	C13H16N4O
CAS No.	912444-00-9

Storage & Solubility 

Storage

Powder: -20°C for 3 years In solvent: -80°C for 2 years

Solubility Information

H2O: <1 mg/mL Ethanol: <1 mg/mL DMSO: 29 mg/mL(118.7 mM) ( < 1 mg/ml refers to the product slightly soluble or insoluble )

References & Literature 

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.

2. Liu F, et al. Effects of poly (ADP-ribose) polymerase-1 (PARP-1) inhibition on sulfur mustard-induced cutaneous injuries in vitro and in vivo. PeerJ. 2016 Apr 4;4:e1890.

3. 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.

4. Mao K, Chen J, Yu H, et al. Poly (ADP‐ribose) polymerase 1 inhibition prevents neurodegeneration and promotes α‐synuclein degradation via transcription factor EB‐dependent autophagy in mutant α‐synucleinA53T model of Parkinson's disease[J]. Aging Cell. 2020: e13163.

5. Epub 2020 May 31. PARP1 inhibition prevents neurodegeneration and promotes α-synuclein degradation via TFEB-dependent autophagy in mutant α-synucleinA53T model of Parkinson's disease. aging cell. 2020 Jun;19(6):e13163

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