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    Veliparib (ABT-888)
    Veliparib (ABT-888)

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    This product is for research use only, not for human use. We do not sell to patients.
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    InvivoChem Cat #: V0301
    CAS #: 912444-00-9 Purity ≥98%

    Description: Veliparib (also known as ABT888; ABT-888) is a novel and potent inhibitor of PARP1 and PARP2 [Poly (ADP-Ribose) Polymerase] with potential anticancer activity. It inhibits PARP1/2 with Ki values of 5.2 nM and 2.9 nM in cell-free assays, respectively. It is being investigated by Abbvie for the treatment of BRCA breast cancer and ovarian cancer. Veliparib also has chemosensitizing and antitumor activities, and is inactive against SIRT2. ABT-888 has demonstrated excellent in vivo efficacy in a broad spectrum of preclinical tumor models in combination with a variety of cytotoxic agents. ABT-888 is also active on microsatellite instability (MSI) cell lines harboring mutations in both MRE11 and RAD50 genes compared to microsatellite stable (MSS) cell lines (wild-type for both genes). ABT-888 has no antiproliferative effects as a single agent at therapeutic concentrations, ABT-888 inhibits PARPs, thereby inhibiting DNA repair and potentiating the cytotoxicity of DNA-damaging agents.

    References: Clin Cancer Res. 2007 May 1;13(9):2728-37; Clin Cancer Res. 2007 May 15;13(10):3033-42; Clin Cancer Res. 2008 Nov 1; 14(21): 6877–6885.

    Related CAS: 912445-05-7 (Veliparib dihydrochloride); 912444-00-9 (free base) 

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    Molecular Weight (MW)244.29
    CAS No.912444-00-9 (free base); 
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 17 mg/mL (69.6 mM)     
    Water: <1 mg/mL
    Ethanol: <1 mg/mL
    Solubility (In vivo)0.5% methylcellulose+0.2% Tween 80: 5 mg/mL

    NSC 737664; NSC737664; NSC-737664; ABT888; ABT-888; ABT 888; Veliparib hydrochloride; Veliparib HCl;

    Chemical Name: (R)-2-(2-methylpyrrolidin-2-yl)-1H-benzo[d]imidazole-4-carboxamide

    SMILES Code: O=C(C1=C2C(NC([[email protected]]3(C)NCCC3)=N2)=CC=C1)N 

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    In Vitro

    In vitro activity: ABT-888 is inactive to SIRT2 (>5 μM). ABT-888 inhibits the PARP activity with EC50 of 2 nM in C41 cells. ABT-888 could decrease the PAR levels in both irradiated and nonirradiated H460 cells. ABT-888 also reduces clonogenic survival and inhibits DNA repair by PARP-1 inhibition in H460 cells. ABT-888 increases apoptosis and autophagy in H460 cells when combination with radiation. ABT-888 also inhibits PARP activity in H1299, DU145 and 22RV1 cells and the inhibition is independent of p53 function. ABT-888 (10 μM) suppresses the surviving fraction (SF) by 43% in the clonogenic H1299 cells. ABT-888 shows effective radiosensitivity in oxic H1299 cells. Furthermore, ABT-888 could attenuate the SF of hypoxic-irradiated cells including H1299, DU145 and 22RV1.

    Kinase Assay: PARP assays are conducted in a buffer containing 50 mM Tris (pH 8.0), 1 mM DTT, 1.5 μM [3H]NAD+ (1.6 μCi/mmol), 200 nM biotinylated histone H1, 200 nM slDNA, and 1 nM PARP-1 or 4 nM PARP-2 enzyme. Reactions are terminated with 1.5 mM benzamide, transferred to streptavidin Flash plates, and counted using a TopCount microplate scintillation counter.

    Cell Assay: In HCT-116 and HT-29 cell lines, the ability of ABT-888 to synergize the effect of the anti-cancer agents, SN38 or oxaliplatin, was determined using the SRB assay. PARP activity was significantly reduced in samples treated with SN38 in combination with ABT-888 (>4 fold at 24 h).

    In VivoThe oral bioavailability of ABT-888 is 56%-92% in mice, Sprague-Dawley rats, beagle dogs, and cynomolgus monkeys after oral administration. ABT-888 (25 mg/kg i.p.) could improve tumor growth delay in a NCI-H460 xenograft model with well tolerated. Combination with radiation, ABT-888 decreases the tumor vessel formation. ABT-888 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 could be maintained over time.
    Animal modelFemale nude athymic mice
    Formulation & DosageDissolved in solution containing 0.9% NaCl adjusted to pH 4.0;  55mg/kg;  Oral administration
    ReferencesClin Cancer Res. 2007 May 1;13(9):2728-37; Clin Cancer Res. 2007 May 15;13(10):3033-42; Clin Cancer Res. 2008 Nov 1; 14(21): 6877–6885.

    These protocols are for reference only. InvivoChem does not independently validate these methods.


    Veliparib (ABT-888)


    Veliparib (ABT-888)


    Veliparib (ABT-888)


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