Ceritinib ldk378

Manufactured by Selleck Chemicals

Sourced in United States

Ceritinib (LDK378) is a chemical compound used in laboratory research. It is a tyrosine kinase inhibitor that targets the ALK (anaplastic lymphoma kinase) protein. Ceritinib is commonly used in scientific studies to investigate its effects on cellular processes and potential therapeutic applications.

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6 protocols using ceritinib ldk378

Kinase Inhibitors and Interferon-gamma Assay

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The following inhibitors were used: Crizotinib (PF-02341066) (Selleckchem S106), Ceritinib (LDK378) (Selleckchem S7083), Alectinib (CH5424802) (Selleckchem S2762), Lorlatinib (PF-6463922) (Selleckchem S7536), Selumetinib (AZD6244) (Selleckchem S1008), Trametinib (GSK1120212) (Selleckchem S2673), Tofacitinib Citrate (CP-690550) (Selleckchem S5001), AZD1480 (Selleckchem S2162), Rapamycin (Selleckchem S1039), LY294002 (Selleckchem S1105), JNK-IN-8 (Selleckchem S4901), Ro-31-8220 (Selleckchem 7207), AZD5363 (Selleckchem S8017), Ipatasertib (Selleckchem S2808), SCH772984 (Selleckchem S7101), Ulixertinib (Selleckchem S7854). BKM120 and Tepp-46 were kind gifts from Dr. Thomas Craig, NCI, Bethesda, Maryland, USA; recombinant human interferon-gamma, IFNγ (BioLegend 570208).

Rajan S.S., Amin A.D., Li L., Rolland D.C., Li H., Kwon D., Kweh M.F., Arumov A., Roberts E.R., Yan A., Basrur V., Elenitoba-Johnson K.S., Chen X.S., Puvvada S.D., Lussier Y.A., Bilbao D., Lim M.S, & Schatz J.H. (2019). The Mechanism of Cancer Drug Addiction in ALK-Positive T-Cell Lymphoma. Oncogene, 39(10), 2103-2117.

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Small Molecule Kinase Inhibitor Assay

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Alectinib (CH5424802), ceritinib (LDK378), crizotinib, erlotinib, AZD9291, AZD 8931, afatinib, AP26113, and PF06463922 were purchased from Selleckchem (Houston, TX). Epithelial growth factor (EGF), amphiregulin, neuregulin-1 (NRG1), and insulin growth factor (IGF) were purchased from R&D systems (Minneapolis, MN). All reagents were stored at − 20°C.

Dong X., Fernandez-Salas E., Li E, & Wang S. (2016). Elucidation of Resistance Mechanisms to Second-Generation ALK Inhibitors Alectinib and Ceritinib in Non–Small Cell Lung Cancer Cells. Neoplasia (New York, N.Y.), 18(3), 162-171.

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Kinase Inhibitors and Interferon-gamma Assay

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Ceritinib and Crizotinib Cytotoxicity Assay

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Ceritinib (LDK-378) and Crizotinib (PF-02341066) were purchased from Selleckchem.com and prepared according to the manufacturer’s guidelines. Drugs were diluted in DMSO to the defined concentrations. Cells were seeded at 5,000 cells/well in a 96-well plate and allowed to adhere for 24 h. After 24 h, the appropriate drug concentration was added to each well and the plates incubated at 37 °C and 5% CO2 for 48 h. The fluorescence intensity was measured using a Spectramax Gemini plate reader (Molecular Devices, San Jose, CA, USA) using an excitation wavelength of 530 nm and an emission wavelength of 580 nm. Analysis was completed by normalizing intensity values against wells containing media alone. Data was represented as mean of each condition. No detectable batch effect was observed.

Guerreiro Stucklin A.S., Ryall S., Fukuoka K., Zapotocky M., Lassaletta A., Li C., Bridge T., Kim B., Arnoldo A., Kowalski P.E., Zhong Y., Johnson M., Li C., Ramani A.K., Siddaway R., Nobre L.F., de Antonellis P., Dunham C., Cheng S., Boué D.R., Finlay J.L., Coven S.L., de Prada I., Perez-Somarriba M., Faria C.C., Grotzer M.A., Rushing E., Sumerauer D., Zamecnik J., Krskova L., Garcia Ariza M., Cruz O., Morales La Madrid A., Solano P., Terashima K., Nakano Y., Ichimura K., Nagane M., Sakamoto H., Gil-da-Costa M.J., Silva R., Johnston D.L., Michaud J., Wilson B., van Landeghem F.K., Oviedo A., McNeely P.D., Crooks B., Fried I., Zhukova N., Hansford J.R., Nageswararao A., Garzia L., Shago M., Brudno M., Irwin M.S., Bartels U., Ramaswamy V., Bouffet E., Taylor M.D., Tabori U, & Hawkins C. (2019). Alterations in ALK/ROS1/NTRK/MET drive a group of infantile hemispheric gliomas. Nature Communications, 10, 4343.

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Preparation of ALK Inhibitor Compounds

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For laboratory assessment, the compounds crizotinib (PF-02341066, Cat. No. S1068, Selleck Chemicals LLC, Houston, TX, USA), ceritinib (LDK378, Cat. No. S7083, Selleck Chemicals LLC, Houston, TX, USA) and lorlatinib (PF-6463922, Cat. No. S7536, Selleck Chemicals LLC, Houston, TX, USA) were prepared as stock solutions of 5 mM in DMSO (J.T. Baker, Avantor Performance Materials Poland S.A., Gliwice, Poland).

Aydemirli M.D., van Eendenburg J.D., van Wezel T., Oosting J., Corver W.E., Kapiteijn E, & Morreau H. (2021). Targeting EML4-ALK gene fusion variant 3 in thyroid cancer. Endocrine-Related Cancer, 28(6), 377-389.

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Ceritinib Inhibits ABCB1 and Enhances Drug Sensitivity

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Ceritinib (LDK378) was purchased from Selleck Chemical (Houston, TX, USA). The molecular structure of ceritinib is shown in Fig. 1A. Monoclonal antibody against ABCB1, extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), p-ERK, AKT and p-AKT were purchased from Santa Cruz Biotechnology (Santa Cruz, CA, USA). The antibody against glyceraldehyde-3-Phosphate dehydrogenase (GAPDH) was purchased from Kangcheng (Shanghai, China). RPMI-1640 and fetal bovine serum (FBS) were obtained from Gibco BRL (Thermo Fisher Scientific Inc., Waltham, MA, USA). Lymphocyte separation medium was from Zhanchen Inc. (Shanghai, China). Doxorubicin (Dox), paclitaxel, cisplatin, verapamil (VRP), dimethyl sulfoxide (DMSO), rhodamine123, and 3-(4, 5-dimethylthiazol-2yl)-2, 5-diphenyl tetrazolium bromide (MTT), were all purchased from Sigma-Aldrich (St. Louis, MO, USA).

Yang L., Li M., Wang F., Zhen C., Luo M., Fang X., Zhang H., Zhang J., Li Q, & Fu L. (2018). Ceritinib Enhances the Efficacy of Substrate Chemotherapeutic Agent in Human ABCB1-Overexpressing Leukemia Cells In Vitro, In Vivo and Ex-Vivo. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 46(6).

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