|
受注：045-509-1970 |
技術サポート：tech@selleck.co.jp 平日9:00〜18:00 1営業日以内にご連絡を差し上げます |
化学情報
|
Synonyms | N/A | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
| 化学式 | C22H23ClFN5O3 |
|||
| 分子量 | 459.90 | CAS No. | 1626387-80-1 | |
| Solubility (25°C)* | 体外 | DMSO | 92 mg/mL (200.04 mM) | |
| Ethanol | 44 mg/mL warmed with 50ºC water bath (95.67 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. |
||||
溶剤液（一定の濃度）を調合する
生物活性
| 製品説明 | Zorifertinib (AZD3759) is a potent, oral active, CNS-penetrant EGFR inhibitor with IC50 of 0.3 nM, 0.2 nM, and 0.2 nM for EGFR (WT), EGFR (L858R), and EGFR (exon 19Del), respectively. Phase 1. |
|---|---|
| in vitro | In H3255 (L858R) cells, AZD3759 inhibits EGFR phosphorylation with IC50 of 7.2 nM. AZD3759 demonstrates inhibitory effects on both the pEGFR pathway and cell proliferation of EGFR mutation-derived cells PC-9 and H3255 with IC50 of 7.7 nM and 7 nM, respectively, showing mo activity on cell proliferation of H838 cells. [1] |
| in vivo | AZD3759 shows good oral bioavailability in dogs, and penetrates extensively into monkey brain. In a brain metastasis PC-9 (Exon19Del) model, AZD3759 (15 mg/kg) causes significant dose-dependent antitumor efficacy. [1] |
プロトコル(参考用のみ)
| キナーゼアッセイ | IC50 determination of compounds against EGFR enzymes | |
|---|---|---|
| The inhibition potency of compounds against EGFR WT and mutant enzymes is assessed using CisBio homogenous time resolved fluorescence approach (HTRF, Cat No. 62TK0PEJ) according to manufacturer’s instruction. The final enzyme concentrations used in this assay are 0.1 nM, 0.03 nM, and 0.026 nM for EGFR wild type, L858R and Exon19Del, respectively, and 0.8 μM, 4 μM and 25 μM ATP, corresponding to the Km values of EGFR enzymes, are applied accordingly. In brief, 3 μL of ATP and 2 μM TK biotin-peptide substrate are incubated in the presence or absence of serially diluted compound at room temperature in 384-well Greiner white polystyrene assay plates. The reaction is initiated by addition of 3 μL kinase which could phosphorylate the substrate peptide, and the assay buffer contains 1 mM DTT, 5 mM MgCl2, 1 mM MnCl2, and 0.01% CHAPS. After 30 minutes incubation, the reaction is stopped by the addition of 6 μl detection reagent mix containing 250 nM Strep-XL665 and TK Ab Europium Cryptate diluted in detection buffer. The plates are incubated for 1 h before the fluorescence is then measured at 615 nm and 665 nm, respectively with excitation wavelength at 320 nm by EnVision Multilabel Reader from Perkin Elmer using standard HTRF settings. The calculated signal ratio of 665 nm/615 nm is proportional to the kinase activity. The concentration of compound producing 50% inhibition of the respective kinase (IC50) is calculated using four-parameter logistic fit. | ||
| 細胞アッセイ | 細胞株 | PC-9 (exon 19Del), H3255 (L858R) and H838 (wt) cells |
| 濃度 | ~30 mM | |
| 反応時間 | 72 h | |
| 実験の流れ | Cell proliferation assay is determined by MTS methods. Briefly, cells are seeded in 96-well plates (at a density to allow for logarithmic growth during the 72-hour assay) and incubated overnight at 37 °C and 5% CO2. Cells are then exposed to concentrations of compounds ranging from 30 to 0.0003 mM for 72 hours. For the MTS endpoint, cell proliferation is measured by the CellTiter AQueous Non-Radioactive Cell Proliferation Assay reagent in accordance with the manufacturer’s protocol. Absorbance is measured with a Tecan Ultra instrument. Predose measurements are made, and concentration needed to reduce the growth of treated cells to half that of untreated cells (GI50) values are determined using absorbance readings. | |
| 動物実験 | 動物モデル | Mice bearing PC-9 (Exon19Del) tumors |
| 投薬量 | ~15 mg/kg | |
| 投与方法 | p.o. | |
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：
| A Novel Network Pharmacology Strategy Based on the Universal Effectiveness-Common Mechanism of Medical Herbs Uncovers Therapeutic Targets in Traumatic Brain Injury [ Drug Des Devel Ther, 2024, 18:1175-1188] | PubMed: 38645986 |
| Aurora kinase blockade drives de novo addiction of cervical squamous cell carcinoma to druggable EGFR signalling [ Oncogene, 2022, 10.1038/s41388-022-02256-3] | PubMed: 35250028 |
| Patient-derived organoids and orthotopic xenografts of primary and recurrent gliomas represent relevant patient avatars for precision oncology [ Acta Neuropathol, 2020, 10.1007/s00401-020-02226-7] | PubMed: 33009951 |
| YH25448, an Irreversible EGFR-TKI with Potent Intracranial Activity in EGFR Mutant Non-Small Cell Lung Cancer [ Clin Cancer Res, 2019, 25(8):2575-2587] | PubMed: 30670498 |
| IP1867B suppresses the insulin-like growth factor 1 receptor (IGF1R) ablating epidermal growth factor receptor inhibitor resistance in adult high grade gliomas [ Cancer Lett, 2019, 458:29-38] | PubMed: 31129148 |
| Brain distribution of a panel of EGFR inhibitors using cassette-dosing in wild-type and Abcb1/Abcg2 deficient mice [Kim M Drug Metab Dispos, 2019, 10.1124/dmd.118.084210] | PubMed: 30705084 |
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。