Ceritinib

SKU: orb1307443

Description

Ceritinib (LDK378) is a potent, orally active, and ATP-competitive small molecule inhibitor primarily targeting ALK with an IC50 of 200 pM, while also inhibiting IGF-1R, InsR, and STK22D. It demonstrates antitumor activity and is widely used in cancer research, particularly in studies of ALK-rearranged non-small cell lung cancer, both in vitro and in vivo.

Research Area

Cardiovascular Research, Pharmacology & Drug Discovery, Protein Biochemistry, Signal Transduction

Key Properties

• CAS Number: 1032900-25-6
• MW: 558.14
• Purity: >99.99% (May vary between batches)
• Formula: C₂₈H₃₆ClN₅O₃S
• SMILES: N(C1=C(OC(C)C)C=C(C(C)=C1)C2CCNCC2)C=3N=C(NC4=C(S(C(C)C)(=O)=O)C=CC=C4)C(Cl)=CN3
• Target: IGF-1R,ALK,Serine Protease
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:0.8 mg/mL (1.43 mM);H2O:< 1 mg/mL (insoluble or slightly soluble);DMSO:16 mg/mL (28.67 mM);Ethanol:3 mg/mL (5.37 mM)

Bioactivity

• Target IC50:
  ALK:0.2 nM (cell free)|STK22D:23 nM (cell free)|IGF-1R:8 nM (cell free)|Insulin receptor:7 nM (cell free)
• In Vivo:
  METHODS: To assay anti-tumor activity in vivo, Ceritinib (25 mg/kg, administered orally) and paclitaxel (20 mg/kg, administered intraperitoneally) were administered four times every three days to nude mice bearing KBv200 xenografts. RESULTS: No significant differences in tumor size were found between animals treated with saline, Ceritinib or paclitaxel, respectively. However, the combination of Ceritinib and paclitaxel had a significant inhibitory effect on tumor growth compared to the other groups.
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• In Vitro:
  METHODS: A panel of tumor cells and multidrug resistant (MDR) cells were treated with Ceritinib (0.01-10 µM) for 72 h. Cell viability was measured by MTT assay. RESULTS: The IC50 values of KB, KBv200, MCF-7, MCF-7/adr, S1, S1-M1-80, HEK293/pcDNA3.1, HEK293/ABCB1 and HEK293/ABCG2-R2 cells were 1.10±0.31, 1.69±0.41, 2.15±0.33, 2.73±0.46, 1.34±0.35, 1.69±0.39, 1.50±0.37, 1.86±0.34, 2.84±0.56 µM. Based on the cytotoxicity profile, more than 85% of the cells survived at 0.5 µM Ceritinib concentration. METHODS: Human breast cancer cell lines MDA-MB 453 and MFM223 were treated with Ceritinib (10 µM) for 15 min-4 h. Target protein expression levels were measured by Western Blot. RESULTS: Ceritinib treatment down-regulated AR, ACK1, HER2, and HER3 in MDA-MB-453 and MFM223 cells in a time-dependent manner.
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• Cell Research:
  Luciferase-expressing cells were incubated with serial dilutions of compounds or DMSO for 2–3 days. Luciferase expression was used as a measure of cell proliferation/survival and was evaluated with the Bright-Glo Luciferase Assay System. IC50 values were generated by using XLFit software .
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• Animal Research:
  SCID beige mice for crizotinib-resistant H2228 xenograft tumor models, nude mice for MGH006 primary explants and MGH045 cells were randomized into groups of 5, 6 or 8 mice with an average tumor volume of ~150 mm^3 and received Crizotinib or ceritinib daily treatments by oral gavage as indicated in each study. Tumor volumes were determined by using caliper measurements and calculated with the formula (Length × Width × Height)/2 .
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Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Ceritinib, CD246, Cluster of differentiation 246, Anaplastic lymphoma kinase (ALK), Anaplastic lymphoma kinase, ALK, ALK tyrosine kinase receptor, inhibit, IGF-1R, IGF1R, Inhibitor, Insulin Receptor, LDK 378, LDK378, LDK-378, Serine Protease, SerineProtease, STK22D

Compound Identifiers

PubChem CID

57379345