Home Protein Tyrosine Kinase ALK inhibitor - IGF-1R inhibitor - Serine/threonin kinase inhibitor Ceritinib dihydrochloride For research use only.

Ceritinib dihydrochloride

Synonyms: Zykadia, LDK378 dihydrochloride

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.

Ceritinib dihydrochloride Chemical Structure

Ceritinib dihydrochloride Chemical Structure

CAS No. 1380575-43-8

Purity & Quality Control

Ceritinib dihydrochloride Related Products

Signaling Pathway

ALK Signaling Pathways

ALK Signaling Pathway

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
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]
Kinase Assay 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 Research 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.
In Vivo
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]
Animal Research Animal Models RNU nude rats bearing the Karpas299/H2228 tumors
Dosages ~50 mg/kg
Administration o.g.
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT03087448 Terminated
Non-small Cell Lung Cancer
University of California San Francisco|Novartis Pharmaceuticals|University of California Davis
 September 9 2017 Phase 1
NCT02638909 Terminated
Colorectal Adenocarcinoma|Cholangiocarcinoma|Pancreatic Adenocarcinoma|Hepatocellular Adenocarcinoma|Gastric Adenocarcinoma|Esophageal Adenocarcinoma
Criterium Inc.|University of Colorado Denver|Novartis
 December 2015 Phase 2
NCT02422589 Completed
ALK-positive Advanced Tumors
Novartis Pharmaceuticals|Novartis
 October 23 2015 Phase 1

Chemical Information & Solubility

Molecular Weight 631.06 Formula

C28H38Cl3N5O3S
CAS No. 1380575-43-8 SDF --
Smiles Cl.Cl.CC(C)OC1=C(NC2=NC=C(Cl)C(=N2)NC3=CC=CC=C3[S](=O)(=O)C(C)C)C=C(C)C(=C1)C4CCNCC4
Storage (From the date of receipt) 3 years -20°C powder

In vitro
Batch:

DMSO : 13 mg/mL ( (20.6 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 10 mg/mL

Water : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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