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Synonyms | ATR inhibitor IV | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C18H16N4O3S |
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分子量 | 368.41 | CAS No. | 1232410-49-9 | |
Solubility (25°C)* | 体外 | DMSO | 74 mg/mL (200.86 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 | VE-821(ATR inhibitor IV) is a potent and selective ATP competitive inhibitor of ATR with Ki/IC50 of 13 nM/26 nM in cell-free assays, shows inhibition of H2AX phosphorylation, minimal activity against PIKKs ATM, DNA-PK, mTOR and PI3Kγ. |
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in vitro | VE-821(ATR inhibitor IV) shows excellent selectivity for ATR with minimal cross-reactivity against the related PIKKs ATM, DNA-PK, mTOR and PI3K (Kis of 16 μM, 2.2 μM, >1 μM and 3.9 μM, respectively. VE-821 alone commits a large fraction of cancer cell populations to death, but it only reversibly limits cell cycle progression in normal cells, with minimal death or long-term detrimental effects. VE-821 along with cisplatin treatment shows the most marked synergy. [1] VE-821(ATR inhibitor IV) inhibits H2AX cell growth with IC50 of 800 nM. [2] |
in vivo | VE-821(ATR inhibitor IV) is a potent and selective ATP competitive inhibitor of ATR. |
キナーゼアッセイ | Kinase inhibition | |
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The ability of compounds to inhibit ATR, ATM or DNAPK kinase activity istested using a radiometric-phosphate incorporation assay. A stock solution isprepared consisting of the appropriate buffer, kinase, and target peptide. To this isadded the compound of interest, at varying concentrations in DMSO to a final DMSO concentration of 7%. Assays are initiated by addition of an appropriate [γ-33P]ATP solution and incubated at 25 ℃. Assays are stopped, after the desired time course, by addition of phosphoric acid and ATP to a final concentration of 100 mM and 0.66μM, respectively. Peptides are captured on a phosphocellulose membrane, prepared as per manufacturer | ||
細胞アッセイ | 細胞株 | H2AX cells |
濃度 | -- | |
反応時間 | 96 hours | |
実験の流れ | Cells are plated in 96-well plates and allowed to adhere overnight. The following day, compounds are added at the indicated concentrations in a final volume of 200μL, and the cells are then incubated for 96 h. MTS reagent (40μL) isthen added, and 1 h later, absorbance at 490 nm ismeasured using a SpectraMax Plus 384 plate reader. Synergy and antagonism are assessed using Macsynergy software. |
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動物実験 | 動物モデル | Male immunodefcient mice |
投薬量 | 15 mg/kg | |
投与方法 | i.p. |
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Data from [Data independently produced by Toxicol Sci, 2014, 10.1093/toxsci/kfu207]
Data from [Data independently produced by J Biol Chem, 2014, 289(35), 24314-24]
Data from [Data independently produced by , , Nature, 2018, 555(7696):387-391]
Comprehensive multi-omics analysis reveals WEE1 as a synergistic lethal target with hyperthermia through CDK1 super-activation [ Nat Commun, 2024, 15(1):2089] | PubMed: 38453961 |
Immunomodulatory effects and improved outcomes with cisplatin- versus carboplatin-based chemotherapy plus atezolizumab in urothelial cancer [ Cell Rep Med, 2024, 5(2):101393] | PubMed: 38280376 |
ATR limits Rad18-mediated PCNA monoubiquitination to preserve replication fork and telomerase-independent telomere stability [ EMBO J, 2024, 43(7):1301-1324] | PubMed: 38467834 |
DNA damage remodels the MITF interactome to increase melanoma genomic instability [ Genes Dev, 2024, 38(1-2):70-94] | PubMed: 38316520 |
The ARID1A-METTL3-m6A axis ensures effective RNase H1-mediated resolution of R-loops and genome stability [ Cell Rep, 2024, 43(2):113779] | PubMed: 38358891 |
Large tandem duplications in cancer result from transcription and DNA replication collisions [ medRxiv, 2024, 2023.05.17.23290140] | PubMed: 38260434 |
Polθ is phosphorylated by PLK1 to repair double-strand breaks in mitosis [ Nature, 2023, 621(7978):415-422] | PubMed: 37674080 |
ATM signaling modulates cohesin behavior in meiotic prophase and proliferating cells [ Nat Struct Mol Biol, 2023, 10.1038/s41594-023-00929-5] | PubMed: 36879153 |
CDC7 inhibition induces replication stress-mediated aneuploid cells with an inflammatory phenotype sensitizing tumors to immune checkpoint blockade [ Nat Commun, 2023, 10.1038/s41467-023-43274-3] | PubMed: 37980406 |
ATM-ESCO2-SMC3 axis promotes 53BP1 recruitment in response to DNA damage and safeguards genome integrity by stabilizing cohesin complex [ Nucleic Acids Res, 2023, gkad533] | PubMed: 37377435 |
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。
各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。