Ceritinib dihydrochloride

Catalog No.S4967 Batch:S496701

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Technical Data

Formula

C28H38Cl3N5O3S
Molecular Weight 631.06 CAS No. 1380575-43-8
Solubility (25°C)* In vitro DMSO 13 mg/mL (20.6 mM)
Ethanol 10 mg/mL (15.84 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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description 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.
Targets
ALK [1]
(Cell-free assay)		 InsR [1]
(Cell-free assay)		 IGF-1R [1]
(Cell-free assay)		 STK22D [1]
(Cell-free assay)
0.2 nM 7 nM 8 nM 23 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. [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]

Protocol (from reference)

Kinase Assay:

[2]
  • 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:

[2]
  • 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:

[2]
  • Animal Models

    RNU nude rats bearing the Karpas299/H2228 tumors

  • Dosages

    ~50 mg/kg

  • Administration

    o.g.

Selleck's Ceritinib dihydrochloride has been cited by 16 publications

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

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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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