受注:045-509-1970 |
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Synonyms | NSC 737664 | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C13H16N4O |
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分子量 | 244.29 | CAS No. | 912444-00-9 | |
Solubility (25°C)* | 体外 | DMSO | 49 mg/mL (200.58 mM) | |
Water | Insoluble | |||
Ethanol | Insoluble | |||
* <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. |
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. |
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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. |
キナーゼアッセイ | In vitro PARP assays | |
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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 |
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]
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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