Ceritinib

製品コードS7083 バッチS708305

印刷

化学情報

Chemical Structure Synonyms LDK378 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C28H36ClN5O3S
分子量 558.14 CAS No. 1032900-25-6
Solubility (25°C)* 体外 Ethanol 5 mg/mL (8.95 mM)
DMSO (warmed with 50ºC water bath) 3 mg/mL (5.37 mM)
Water Insoluble
体内 （毎回新しく調製した物を用意してください）
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O
0.15mg/ml Taking the 1 mL working solution as an example, add 50 μL 3 mg/ml clarified DMSO stock solution to 400 μL PEG300, mix evenly to clarify it; add 50 μL Tween80 to the above system, mix evenly to clarify it; then continue to add 500 μL ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <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 Ceritinib is a potent inhibitor against ALK with IC50 of 0.2 nM in cell-free assays. Ceritinib (LDK378) also inhibits IGF-1R, InsR, STK22D and FLT3 with IC50 of 8 nM, 7 nM, 23 nM and 60 nM, respectively. Phase 3.
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. [1]
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. [1]
特徴 Does not cross react with c-Met, and has an improved in vivo glucose homeostasis profile relative to TAE684. May be active in Crizotinib-relapsed tumors.

プロトコル(参考用のみ)

キナーゼアッセイ Enzymatic kinase profiling description
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.
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 Oral gavage

カスタマーフィードバック

Data from [Data independently produced by , , Cancer Cell, 2015, 27(3): 397-408 ]

Data from [Data independently produced by , , Cell Res, 2015, 25(4): 445-58]

Data from [Data independently produced by , , Clin Cancer Res, 2018, doi:10.1158/1078-0432]

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：

Multi-omic and functional analysis for classification and treatment of sarcomas with FUS-TFCP2 or EWSR1-TFCP2 fusions [ Nat Commun, 2024, 15(1):51] PubMed: 38168093
A small-molecule degrader selectively inhibits the growth of ALK-rearranged lung cancer with ceritinib resistance [ iScience, 2024, 27(2):109015.] PubMed: 38327793
Combination Therapies Targeting ALK-aberrant Neuroblastoma in Preclinical Models [ Clin Cancer Res, 2023, 29(7):1317-1331] PubMed: 36602782
Crizotinib Has Preclinical Efficacy in Philadelphia-Negative Myeloproliferative Neoplasms [ Clin Cancer Res, 2023, 29(5):943-956] PubMed: 36537918
Tyrosine Kinase Inhibitors Target B Lymphocytes [ Biomolecules, 2023, 13(3)438] PubMed: 36979373
Preclinical evidence for anaplastic lymphoma kinase inhibitors as novel therapeutic treatments for cholangiocarcinoma [ Front Oncol, 2023, 13:1184900] PubMed: 38144528
Inhibition of the epigenetically activated miR-483-5p/IGF-2 pathway results in rapid loss of meningioma tumor cell viability [ J Neurooncol, 2023, 162(1):109-118.] PubMed: 36809604
Iruplinalkib (WX‑0593), a novel ALK/ROS1 inhibitor, overcomes crizotinib resistance in preclinical models for non-small cell lung cancer [ Invest New Drugs, 2023, 41(2):254-266] PubMed: 37036582
SHP2 Inhibition with TNO155 Increases Efficacy and Overcomes Resistance of ALK Inhibitors in Neuroblastoma [ Cancer Res Commun, 2023, 3(12):2608-2622] PubMed: 38032104
Analysis of lorlatinib analogs reveals a roadmap for targeting diverse compound resistance mutations in ALK-positive lung cancer [ Nat Cancer, 2022, 3(6):710-722] PubMed: 35726063

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。