Ceritinib

Catalog No.S7083 Batch:S708304

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Technical Data

Formula

C28H36ClN5O3S
Molecular Weight 558.14 CAS No. 1032900-25-6
Solubility (25°C)* In vitro DMSO 4 mg/mL (7.16 mM)
Water Insoluble
Ethanol 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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description 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.
Targets
ALK [1]
(Cell-free assay)		 Insulin Receptor [1]
(Cell-free assay)		 IGF-1R [1]
(Cell-free assay)		 STK22D [1]
(Cell-free assay)		 FLT3 [1]
(Cell-free assay)
0.2 nM 7 nM 8 nM 23 nM 60 nM
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]
Features 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.

Protocol (from reference)

Kinase Assay:[1]
  • 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)
Cell Assay:[1]
  • Cell lines

    Ba/F3-NPM-ALK, Ba/F3-Tel-InsR, Ba/F3-WT, Karpas299 cells

  • Concentrations

    ~100 μM

  • Incubation Time

    2-3 days

  • Method

    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.
Animal Study:[1]
  • Animal Models

    RNU nude rats bearing the Karpas299/H2228 tumors

  • Dosages

    ~50 mg/kg

  • Administration

    Oral gavage

Customer Product Validation

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]

Data from [Data independently produced by , , Clin Cancer Res, 2018, 24(17):4162-4174]

Selleck's Ceritinib has been cited by 114 publications

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

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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