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受注：045-509-1970 |
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化学情報
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Synonyms | N/A | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
| 化学式 | C15H18BrN7 |
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| 分子量 | 376.25 | CAS No. | 891494-63-6 | |
| Solubility (25°C)* | 体外 | DMSO | 3 mg/mL (7.97 mM) | |
| Water | Insoluble | |||
| Ethanol | Insoluble | |||
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* <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. |
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溶剤液（一定の濃度）を調合する
生物活性
| 製品説明 | MK-8776 (SCH 900776) is a selective Chk1 inhibitor with IC50 of 3 nM in a cell-free assay. It shows 500-fold selectivity against Chk2. Phase 2. |
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| in vitro | SCH 900776 is a less potent inhibitor of Chk2 and CDK2 with IC50 of 1.5 μM and 0.16 μM, respectively. SCH 900776 shows no significant inhibition of cytochrome P450 human liver microsomal isoforms 1A2, 2C9, 2C19, 2D6, and 3A4. SCH 900776 induces a dose-dependent loss of DNA replication capability 24 hours after hydroxyurea exposure. SCH 900776 enhances the γ-H2AX response of hydroxyurea, 5-fluoruracil, and cytarabine. In combination with an antimetabolite, SCH 900776 induces accumulation of γ-H2AX within 2 hours, indicative of replication fork collapse and double stranded DNA breaks. Additionally, SCH 900776 suppresses accumulation of the Chk1 pS296 autophosphorylation in a dose-dependent manner. Exposure of proliferating WS1 cells to SCH 900776 is associated with rapid, dose-dependent accumulation of Chk1 pS345, indicating that cycling populations of normal cells induce Chk1 pS345 following exposure to SCH 900776 as part of a futile cycle, perhaps driven by AT-family kinases and DNA-PK.[1] |
| in vivo | Administered 30 minutes after gemcitabine, 4 mg/kg SCH 900776 is sufficient to induce the γ-H2AX biomarker while 8 mg/kg leads to enhanced tumor pharmacodynamic and regression responses relative to gemcitabine or SCH 900776 alone. Dose escalation of SCH 900776 (16 mg/kg and 32 mg/kg) induces incremental improvements in tumor response. Importantly, doses of SCH 900776 associate with robust biomarker activation and improved tumor response are not associated with enhanced toxicity of gemcitabine on hematological parameters in BALB/c mice. [1] |
プロトコル(参考用のみ)
| キナーゼアッセイ | Chk1 SPA assay | |
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| An in vitro assay utilizing recombinant His-Chk1 expressed in the baculovirus expression system as an enzyme source and biotinylated peptide based upon CDC25C as substrate. His-Chk1 is diluted to 32 nM in kinase buffer containing 50 mM Tris pH 8.0, 10 mM MgCl2, and 1 mM DTT. CDC25C (CDC25 Ser216 C-term biotinylated peptide) peptide is diluted to 1.93 μM in kinase buffer. For each kinase reaction, 20 μL of 32 nM Chk1 enzyme solution and 20 μL of 1.926 μM CDC25C are mixed and combined with 10 μL of SCH 900776 diluted in 10% DMSO, making final reaction concentrations of 6.2 nM Chk1, 385 nM CDC25C and 1% DMSO after addition of start solution. The reaction is started by addition of 50 μL of start solution consisting of 2 μM ATP and 0.2 μCi of 33P-ATP, making a final reaction concentration of 1 μM ATP, with 0.2 μCi of 33P-ATP per reaction. Kinase reactions run for 2 hours at room temperature and are stopped by the addition of 100 μL of stop solution consisting of 2 M NaCl, 1% H3PO4, and 5 mg/mL Streptavidin-coated SPA beads. SPA beads are captured using a 96-well GF/B filter plate and a Filtermate universal harvester. Beads are washed twice with 2 M NaCl and twice with 2 M NaCl with 1% phosphoric acid. Signal is then assayed using a TopCount 96-well liquid scintillation counter. Dose-response curves are generated from duplicate 8 point serial dilutions of SCH 900776. IC50 values are derived by nonlinear regression analysis. | ||
| 細胞アッセイ | 細胞株 | mESCs |
| 濃度 | 10 μM | |
| 反応時間 | 1 h | |
| 実験の流れ | Cells were treated with inhibitors or vehicle for 1 hour |
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| 動物実験 | 動物モデル | Female nude mice injected subcutaneously with A2780 or MiaPaCa2 cells |
| 投薬量 | ~50 mg/kg | |
| 投与方法 | Administered intraperitoneally | |
参考
カスタマーフィードバック
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Data from [Data independently produced by , , Biomaterials, 2018, 182:35-43]
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Data from [Data independently produced by , , Cell Death Dis, 2015, 6:e1947.]
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：
| ATR limits Rad18-mediated PCNA monoubiquitination to preserve replication fork and telomerase-independent telomere stability [ EMBO J, 2024, 43(7):1301-1324] | PubMed: 38467834 |
| Natural pentacyclic triterpenoid from Pristimerin sensitizes p53-deficient tumor to PARP inhibitor by ubiquitination of Chk1 [ Pharmacol Res, 2024, 201:107091] | PubMed: 38316371 |
| Transcriptional Differential Analysis of Nitazoxanide-Mediated Anticanine Parvovirus Effect in F81 Cells [ Viruses, 2024, 16(2)282] | PubMed: 38400057 |
| ATR protects ongoing and newly assembled DNA replication forks through distinct mechanisms [ Cell Rep, 2023, 42(7):112792] | PubMed: 37454295 |
| Olaparib-Resistant BRCA2MUT Ovarian Cancer Cells with Restored BRCA2 Abrogate Olaparib-Induced DNA Damage and G2/M Arrest Controlled by the ATR/CHK1 Pathway for Survival [ Cells, 2023, 12(7)1038] | PubMed: 37048111 |
| A function for ataxia telangiectasia and Rad3-related (ATR-kinase in cytokinetic abscission. [ iScience, 2023, 25(7)] | PubMed: None |
| The cGAS/STING/IFN-1 Response in Squamous Head and Neck Cancer Cells after Genotoxic Challenges and Abrogation of the ATR-Chk1 and Fanconi Anemia Axis [ Int J Mol Sci, 2023, 24(19)14900] | PubMed: 37834346 |
| A biscarbene gold(I)-NHC-complex overcomes cisplatin-resistance in A2780 and W1 ovarian cancer cells highlighting pERK as regulator of apoptosis [ Cancer Chemother Pharmacol, 2023, 92(1):57-69] | PubMed: 37272932 |
| Chk1 dynamics in G2 phase upon replication stress predict daughter cell outcome [ Dev Cell, 2022, 57(5):638-653.e5] | PubMed: 35245445 |
| Non-enzymatic function of WRN RECQL helicase regulates removal of topoisomerase-I-DNA covalent complexes and triggers NF-κB signaling in cancer [ Aging Cell, 2022, e13625] | PubMed: 35582959 |
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。