Ceritinib

製品コードS7083 バッチS708305

印刷

化学情報

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）

Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	0.150mg/ml (0.27mM)	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. This compound has relatively good metabolic stability, with moderate CYP3A4 (Midazolam substrate) inhibition and hERG inhibition. It 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. It induces a dose-dependent growth inhibition and tumor regression in the Karpas299 and H2228 rat xenograft models, with no body-weight loss. This chemical 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
キナーゼアッセイ	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 this compound on the enzymatic activity is obtained from the linear progress curves in the absence and presence of this compound 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 this compound 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

参考

https://pubmed.ncbi.nlm.nih.gov/23742252/

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：

RNase1-driven ALK-activation is an oncogenic driver and therapeutic target in non-small cell lung cancer [ Signal Transduct Target Ther, 2025, 10(1):124]	PubMed: 40246819
Targeting proteostasis in multiple myeloma through inhibition of LTK [ Leukemia, 2025, 10.1038/s41375-025-02682-8]	PubMed: 40634511
Brigatinib activates inflammasomes: Implication for immune-related adverse events [ Toxicol Appl Pharmacol, 2025, 498:117310]	PubMed: 40122348
NVL-655 Is a Selective and Brain-Penetrant Inhibitor of Diverse ALK-Mutant Oncoproteins, Including Lorlatinib-Resistant Compound Mutations [ Cancer Discov, 2024, OF1-OF20.]	PubMed: 39269178
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
LTK mutations responsible for resistance to lorlatinib in non-small cell lung cancer harboring CLIP1-LTK fusion [ Commun Biol, 2024, 7(1):412]	PubMed: 38575808
A small-molecule degrader selectively inhibits the growth of ALK-rearranged lung cancer with ceritinib resistance [ iScience, 2024, 27(2):109015.]	PubMed: 38327793
Patient-derived rhabdomyosarcoma cells recapitulate the genetic and transcriptomic landscapes of primary tumors [ iScience, 2024, 27(10):110862]	PubMed: 39319271
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

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。