Veliparib (ABT-888)

製品コードS1004 バッチS100418

印刷

化学情報

Chemical Structure Synonyms NSC 737664 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C13H16N4O
分子量 244.29 CAS No. 912444-00-9
Solubility (25°C)* 体外 DMSO 48 mg/mL (196.48 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Clear solution
5%DMSO 40%PEG 300 5%Tween80 50% ddH2O
5.0mg/ml Taking the 1 mL working solution as an example, add 50 μL of 100 mg/mL clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify; add 50 μL of Tween-80 to the above system, mix evenly to clarify; Then continue to add 500 μL ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Veliparib (ABT-888, NSC 737664) is a potent inhibitor of PARP1 and PARP2 with Ki of 5.2 nM and 2.9 nM in cell-free assays, respectively. It is inactive to SIRT2. Veliparib increases autophagy and apoptosis. Phase 3.
in vitro

ABT-888 is inactive to SIRT2 (>5 μM). [1]

ABT-888 inhibits the PARP activity with EC50 of 2 nM in C41 cells. [2]

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. [3]

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. [4]
in vivo

The oral bioavailability of ABT-888 is 56%-92% in mice, Sprague-Dawley rats, beagle dogs, and cynomolgus monkeys after oral administration. [1]

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. [3]

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. [4]
特徴 Increases the efficacy of common cancer therapies such as radiation and alkylating agents.

プロトコル(参考用のみ)

キナーゼアッセイ In vitro PARP assays
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.
細胞アッセイ 細胞株 Cell-free assays
濃度 Ki of 5.2 and 2.9 nM for PARP1 and PARP2
反応時間
実験の流れ
動物実験 動物モデル NCI-H460, H460, B16F10 and 9L xenografts in C57BL/6 mice
投薬量 ~25 mg/kg
投与方法 Orally administered

カスタマーフィードバック

Data from [Nucl Med Commun, 2011, 32, 1046-1051]

Data from [Nucl Med Commun, 2011, 32(11), 1046-51]

Data from [Nucl Med Commun, 2011, 32(11), 1046-51]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Transcription-replication conflicts underlie sensitivity to PARP inhibitors [ Nature, 2024, 10.1038/s41586-024-07217-2] PubMed: 38509368
Aggregability of the SQSTM1/p62-based aggresome-like induced structures determines the sensitivity to parthanatos [ Cell Death Discov, 2024, 10(1):74] PubMed: 38346947
Thioparib inhibits homologous recombination repair, activates the type I IFN response, and overcomes olaparib resistance [ EMBO Mol Med, 2023, e16235.] PubMed: 36652375
A multi-scale map of protein assemblies in the DNA damage response [ Cell Syst, 2023, S2405-4712(23)00116-3] PubMed: 37220749
NINJ1 is activated by cell swelling to regulate plasma membrane permeabilization during regulated necrosis [ Cell Death Dis, 2023, 10.1038/s41419-023-06284-z] PubMed: 37980412
Targeting CD47-SIRPa axis shows potent preclinical anti-tumor activity as monotherapy and synergizes with PARP inhibition [ NPJ Precis Oncol, 2023, 7(1):69] PubMed: 37468567
DTX3L E3 ligase targets p53 for degradation at poly ADP-ribose polymerase-associated DNA damage sites [ iScience, 2023, 26(4):106444] PubMed: 37096048
Dynamics of endogenous PARP1 and PARP2 during DNA damage revealed by live-cell single-molecule imaging [ iScience, 2023, 26(1):105779] PubMed: 36594010
Venadaparib Is a Novel and Selective PARP Inhibitor with Improved Physicochemical Properties, Efficacy, and Safety [ Mol Cancer Ther, 2023, 22(3):333-342] PubMed: 36808277
The ATR Inhibitor VE-821 Enhances the Radiosensitivity and Suppresses DNA Repair Mechanisms of Human Chondrosarcoma Cells [ Int J Mol Sci, 2023, 24(3)2315] PubMed: 36768638

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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