受注:045-509-1970 |
技術サポート:[email protected] 平日9:00〜18:00 1営業日以内にご連絡を差し上げます |
Synonyms | ARRY704 | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
|
化学式 | C16H17FIN3O4 |
|||
分子量 | 461.23 | CAS No. | 869357-68-6 | |
Solubility (25°C)* | 体外 | DMSO | 92 mg/mL (199.46 mM) | |
Ethanol | 92 mg/mL (199.46 mM) | |||
Water | 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 | AZD8330 (ARRY704) is a novel, selective, non-ATP competitive MEK 1/2 inhibitor with IC50 of 7 nM. Phase 1. |
---|---|
in vitro | AZD8330 potently and strongly inhibits MEK 1/2. AZD8330 has no inhibitory activity against over 200 other kinases including at concentrations up to 10 μM. AZD8330 demonstrates sub-nanomolar potency in mechanistic (pERK) and low to sub-nanomolar potency in functional (proliferation) assays in MEK 1/2 inhibitor sensitive cell lines. [1] |
in vivo | In a Calu-6 rat xenograft pharmacokinetic/pharmacodynamic (PK/PD) model a single, 1.25 mg/kg oral dose of AZD8330 inhibits ERK phosphorylation by > 90% for between 4 and 8 hours. Doses as low as 0.4 mg/kg once daily are sufficient for > 80% tumor growth inhibition in the Calu-6 nude rat xenograft model. In the Calu-6 model, AZD8330 inhibits tumor growth in a dose-dependent fashion, at 0.3 mg/kg and 1.0 mg/kg once daily. [1] |
キナーゼアッセイ | MEK1 enzymatic assays | |
---|---|---|
NH2-terminal hexahistidine tagged, constitutively active MEK1 (S218D, S222D ΔR4F) is expressed in baculovirus-infected Hi5 insect cells and purified by immobilized metal affinity chromatography, ion exchange, and gel filtration. The activity of MEK1 is assessed by measuring the incorporation of [γ- 33P]phosphate from [γ-33P]ATP onto ERK2. The assay is carried out in a 96-well polypropylene plate with an incubation mixture (100 μL) composed of 25 mM HEPES (pH 7.4), 10 mM MgCl2, 5 mM β-glycerolphosphate, 100 μM sodium orthovanadate, 5 mM DTT, 5 nM MEK1, 1 μM ERK2, and 0 to 80 nM AZD8330 (final concentration of 1% DMSO). The reactions are initiated by the addition of 10 μM ATP (with 0.5 μC k[γ-33P]ATP/well) and incubated at room temperature for 45 min. An equal volume of 25% trichloracetic acid is added to stop the reaction and precipitate the proteins. Precipitated proteins are trapped onto glass fiber B filter plates, excess labeled ATP is washed off with 0.5% phosphoric acid, and radioactivity is counted in a liquid scintillation counter. ATP dependence is determined by varying the amount of ATP in the reaction mixture. The data are globally fitted. | ||
細胞アッセイ | 細胞株 | Malme-3M melanoma cells |
濃度 | ~10 μM | |
反応時間 | 1 hour | |
実験の流れ | Malme-3M melanoma cells are plated in 96-wells and treated with various concentrations of AZD8330 for 1 hour at 37 °C. The cells are fixed, permeabilized, and incubated with an anti-phospho-ERK antibody and an anti-ERK 1/2 antibody. Plates are washed and fluorescently-labeled secondary antibodies are added. Plates are analyzed on a LICOR fluorescence imager. The pERK signal is normalized to the total ERK signa |
|
動物実験 | 動物モデル | Female nude rats (NIH rnu/rnu) with Calu-6 cells, nude rats with SW620 cells |
投薬量 | 0.3 mg/kg, 1 mg/kg | |
投与方法 | Oral administration |
|
Data from [Data independently produced by Cell, 2012, 149(3), 656-70]
Data independently produced by , , Dr.Wang from Southern Medical Hospital
, , Dr. Zhang of Tianjin Medical University
Salmonella effector SopB reorganizes cytoskeletal vimentin to maintain replication vacuoles for efficient infection [ Nat Commun, 2023, 14(1):478] | PubMed: 36717589 |
Identification of New Vulnerabilities in Conjunctival Melanoma Using Image-Based High Content Drug Screening [ Cancers (Basel), 2022, 14(6)1575] | PubMed: 35326726 |
Identification and Characterization of a Novel Dual Inhibitor of Indoleamine 2,3-dioxygenase 1 and Tryptophan 2,3-dioxygenase [ Int J Tryptophan Res, 2022, 15:11786469221138456] | PubMed: 36467776 |
CAGE-prox: A Unified Approach for Time-Resolved Protein Activation in Living Systems [ Curr Protoc, 2021, 1(6):e180] | PubMed: 34165886 |
FAM83A Drives PD-L1 Expression via ERK Signaling and FAM83A/PD-L1 Co-Expression Correlates With Poor Prognosis in Lung Adenocarcinoma [ Int J Clin Oncol, 2020, 19] | PubMed: 32430734 |
Time-resolved protein activation by proximal decaging in living systems [Wang J, et al. Nature, 2019, 569(7757):509-513] | PubMed: 31068699 |
[ Cancer Res, 2019, ] | PubMed: 31362929 |
FAM83A signaling induces epithelial-mesenchymal transition by the PI3K/AKT/Snail pathway in NSCLC. [ Aging (Albany NY), 2019, 11(16):6069-6088] | PubMed: 31444970 |
An increased cell cycle gene network determines MEK and Akt inhibitor double resistance in triple-negative breast cancer. [ Sci Rep, 2019, 9(1):13308] | PubMed: 31527768 |
Reduced MEK inhibition preserves genomic stability in naive human embryonic stem cells. [ Nat Methods, 2018, 15(9):732-740] | PubMed: 30127506 |
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。