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受注：045-509-1970 |
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化学情報
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Synonyms | Zykadia, LDK378 dihydrochloride | Storage (From the date of receipt) |
3 years -20°C powder |
| 化学式 | C28H38Cl3N5O3S |
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| 分子量 | 631.06 | CAS No. | 1380575-43-8 | |
| Solubility (25°C)* | 体外 | DMSO | 13 mg/mL (20.6 mM) | |
| Ethanol | 10 mg/mL (15.84 mM) | |||
| Water | 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 | Ceritinib (Zykadia, LDK378) dihydrochloride is a selective, orally bioavailable and ATP-competitive inhibitor of ALK with IC50 of 0.2 nM. Ceritinib dihydrochloride also inhibits InsR, IGF-1R and STK22D with IC50 of 7 nM, 8 nM and 23 nM, respectively. Ceritinib exhibits antitomor activity. |
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| in vitro | LDK378 shows great anti-proliferative activity in Ba/F3-NPM-ALK and Karpas290 cells with IC50 of 26.0 nM and 22.8 nM, compared with IC50 of 319.5 nM and 2477 nM in Ba/F3-Tel-InsR and Ba/F3-WT cells. [2] |
| in vivo | LDK378 is designed to reduce the possibility of forming reactive metabolites and shows undetectable levels of glutathione (GSH) adducts (<1%) in liver microsomes. LDK378 has relatively good metabolic stability, with moderate CYP3A4 (Midazolam substrate) inhibition and hERG inhibition. LDK378 exhibits low plasma clearance in animals (mouse, rat, dog and monkey) compared to liver blood flow, with the oral bioavailability of above 55% in mouse, rat, dog and monkey. LDK378 induces a dose-dependent growth inhibition and tumor regression in the Karpas299 and H2228 rat xenograft models, with no body-weight loss. LDK378 shows no impact on insulin levels or plasma glucose utilization in the mouse upon chronic dosing up to 100 mg/kg. [2] |
プロトコル(参考用のみ)
| キナーゼアッセイ | Enzymatic kinase profiling description | |
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| All kinases are expressed as either Histidine- or GST-tagged fusion proteins using the baculovirus expression technology except for the untagged ERK2 which is produced in E. coli. The kinase activity is measured in the LabChip mobility shift assay. The assay is performed at 30°C for 60 min. The effect of LDK378 on the enzymatic activity is obtained from the linear progress curves in the absence and presence of LDK378 and routinely determines from one reading (end point measurement) | ||
| 細胞アッセイ | 細胞株 | Ba/F3-NPM-ALK, Ba/F3-Tel-InsR, Ba/F3-WT, Karpas299 cells |
| 濃度 | ~100 μM | |
| 反応時間 | 2-3 days | |
| 実験の流れ | Luciferase-expressing cells are incubated with serial dilutions of LDK378 or DMSO for 2-3 days. Luciferase expression is used as a measure of cell proliferation/survival and is evaluated with the Bright-Glo Luciferase Assay System. IC50 values are generated by using XLFit software. |
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| 動物実験 | 動物モデル | RNU nude rats bearing the Karpas299/H2228 tumors |
| 投薬量 | ~50 mg/kg | |
| 投与方法 | o.g. | |
参考
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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：
| Crizotinib attenuates cancer metastasis by inhibiting TGFβ signaling in non-small cell lung cancer cells [ Exp Mol Med, 2022, 54(8):1225-1235] | PubMed: 35999455 |
| Repurposing Ceritinib Induces DNA Damage and Enhances PARP Inhibitor Responses in High-Grade Serous Ovarian Carcinoma [ Cancer Res, 2022, 82(2):307-319] | PubMed: 34810199 |
| STAT3 inhibition suppresses adaptive survival of ALK-rearranged lung cancer cells through transcriptional modulation of apoptosis [ NPJ Precis Oncol, 2022, 6(1):11] | PubMed: 35228642 |
| Establishment and large-scale validation of a three-dimensional tumor model on an array chip for anticancer drug evaluation [ Front Pharmacol, 2022, 13:1032975] | PubMed: 36313330 |
| Novel human-derived EML4-ALK fusion cell lines identify ribonucleotide reductase RRM2 as a target of activated ALK in NSCLC [ Lung Cancer, 2022, 171:103-114] | PubMed: 35933914 |
| Discovery of a novel ALK/ROS1/FAK inhibitor, APG-2449, in preclinical non-small cell lung cancer and ovarian cancer models [ BMC Cancer, 2022, 22(1):752] | PubMed: 35820889 |
| The CLIP1-LTK fusion is an oncogenic driver in non-small-cell lung cancer [ Nature, 2021, 600(7888):319-323] | PubMed: 34819663 |
| Cell Type-specific Adaptive Signaling Responses to KRASG12C Inhibition [ Clin Cancer Res, 2021, 27(9):2533-2548] | PubMed: 33619172 |
| Pharmacological inhibitors of anaplastic lymphoma kinase (ALK) induce immunogenic cell death through on-target effects [ Cell Death Dis, 2021, 12(8):713] | PubMed: 34272360 |
| TPX-0131, a Potent CNS-Penetrant, Next-Generation Inhibitor of Wild-Type ALK and ALK-Resistant Mutations [ Mol Cancer Ther, 2021, molcanther.0221.2021] | PubMed: 34158340 |
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。