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Ldk378

Manufactured by Selleck Chemicals
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LDK378 is a piece of laboratory equipment used for the detection and analysis of chemical compounds. It is designed to provide accurate and reliable measurements of various properties of samples, such as concentration, purity, and composition. The core function of LDK378 is to facilitate the study and characterization of chemical substances in a controlled laboratory setting.

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Lab products found in correlation

Lapatinib, by Selleck Chemicals (3 mentions) Sh sy5y, by American Type Culture Collection (2 mentions) Sk n sh, by American Type Culture Collection (2 mentions) Cycloheximide (chx), by Selleck Chemicals (2 mentions) Ipi 504, by Apexbio (2 mentions) Recombinant human gas6 rgas6, by R&D Systems (2 mentions) 17 aag, by Selleck Chemicals (2 mentions) Crizotinib, by Chemietek (2 mentions) Aew541, by Selleck Chemicals (2 mentions) Mab391, by R&D Systems (2 mentions) Osi 906, by Selleck Chemicals (2 mentions) Crizotinib, by Selleck Chemicals (2 mentions) Ceritinib, by Selleck Chemicals (2 mentions) Doxorubicin, by Merck Group (1 mentions) Vp 16, by Selleck Chemicals (1 mentions) Spectramax i3x multi mode microplate reader, by Molecular Devices (1 mentions) Celltiter glo ctg luminescent cell viability assay, by Promega (1 mentions) Celltiter glo, by Promega (1 mentions) Erlotinib, by Selleck Chemicals (1 mentions) Mubritinib, by Selleck Chemicals (1 mentions)

Spelling variants of this product

Ceritinib (LDK378) (6 citations)

10 protocols using ldk378

1

Growth-inhibitory effects of combined compounds on neuroblastoma cells

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Growth-inhibitory effects of varying concentrations of 6-thio-dG in combination with etoposide (VP-16, Selleckchem, USA), doxorubicin (Merck, Germany) or ceritinib (LDK378, Selleckchem, USA) on neuroblastoma cell lines with TERT rearrangements (CLB-GA, GI-ME-N), high TERT expression (SH-SY5Y) or MYCN amplification (BE(2)-C, IMR-32, Kelly, LS, TR-14) were determined after 96 h of substance incubation using CellTiter-Glo®. A semi-automated substance screening protocol was established on a Biomek 4000 Automated Workstation (Beckman Coulter, Brea, CA, USA). Single or combined compounds in nine different concentrations and DMSO as control were added in triplicates 24 h after the cells were seeded in a 96-well plate at a density of 3000 cells/well. Cell viability was measured after 96 h of substance incubation using a CellTiter-Glo® (CTG) Luminescent Cell Viability Assay (Promega, Madison, WI, USA). In brief, 100 µl CTG-reagent was added to the wells and incubated for 30 min at room temperature. Signals were measured using a SpectraMax® i3x Multi-Mode microplate reader (Molecular Devices, San Jose, CA, USA). Drug synergy was calculated according to the Chou-Talalay combination index method [17 (link), 18 (link)].
Fischer-Mertens J., Otte F., Roderwieser A., Rosswog C., Kahlert Y., Werr L., Hellmann A.M., Berding M., Chiu B., Bartenhagen C, & Fischer M. (2022). Telomerase-targeting compounds Imetelstat and 6-thio-dG act synergistically with chemotherapy in high-risk neuroblastoma models. Cellular Oncology (Dordrecht), 45(5), 991-1003.
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2

Cell Viability Assay of Kinase Inhibitors

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Erlotinib, lapatinib, mubritinib, LDK378, AP26113, lonafarnib, and 10058-F4 were purchased from Selleck Chem (Houston, TX). Cells were seeded in 50 μL of medium in 96-well plates at 8000 cells/well and incubated overnight. Compounds (50 μL) were added to cells and incubated for 48 h. Cell viability was measured using Cell TiterGlo (Promega, Madison, WI). Data was analyzed with GraphPad Prism software (La Jolla, CA) and the half maximal inhibitory concentration (IC50) was determined. Error bars denote standard deviation.
Choong M.L., Yong J., Wang Y, & Lee M.A. (2014). Establishment and Characterization of a Singaporean Chinese Lung Adenocarcinoma Cell Line with Four Copies of the Epidermal Growth Factor Receptor Gene. BioResearch Open Access, 3(4), 176-182.
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3

Characterization of NB cell lines

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The human NB cell line, SK-N-SH and its derivative, SH-SY5Y, were purchased from the American Type Culture Collection (Manassas, VA, USA) and their authenticity confirmed by genotyping. Cells were also confirmed to be Mycoplasma negative. Parental and resistant cells were grown in RPMI media supplemented with 10% FBS and 1% Penicillin/Streptomycin. TAE684 and R428 were synthesized in-house in Dr. Nathanael Gray’s laboratory. 17-AAG, CHX and LDK378 were purchased from Selleck Chemicals (Houston, TX), and IPI-504 was purchased from APExBIO (Houston, TX, USA). Recombinant human GAS6 (rGAS6) was purchased from R&D Systems (Minneapolis, MN, USA, #885-GS-050).
Debruyne D.N., Bhatnagar N., Sharma B., Luther W., Moore N.F., Cheung N.K., Gray N.S, & George R.E. (2015). ALK inhibitor resistance in ALKF1174L-driven neuroblastoma is associated with AXL activation and induction of EMT. Oncogene, 35(28), 3681-3691.
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4

Preparation and Dissolution of Kinase Inhibitors

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X-376 was prepared as described previously14 (link). Crizotinib (ChemieTek, Indianapolis, IN, USA), OSI-906 (Selleck Chemicals, Houston, TX, USA), AEW-541 (Selleck Chemicals, Houston, TX, USA), LDK-378 (Selleck Chemicals, Houston, TX, USA) and Lapatinib (Selleck Chemicals, Houston, TX, USA) were dissolved in DMSO. Erlotinib was synthesized by the Memorial Sloan-Kettering Cancer Center (MSKCC) Organic Synthesis Core. MAb391 (R&D systems, Minneapolis, MN, USA) was dissolved in PBS.
Lovly C.M., McDonald N.T., Chen H., Ortiz-Cuaran S., Heukamp L.C., Yan Y., Florin A., Ozretić L., Lim D., Wang L., Chen Z., Chen X., Lu P., Paik P.K., Shen R., Jin H., Buettner R., Ansén S., Perner S., Brockmann M., Bos M., Wolf J., Gardizi M., Wright G.M., Solomon B., Russell P.A., Rogers T.M., Suehara Y., Red-Brewer M., Tieu R., de Stanchina E., Wang Q., Zhao Z., Johnson D.H., Horn L., Wong K.K., Thomas R.K., Ladanyi M, & Pao W. (2014). Rationale for co-targeting IGF-1R and ALK in ALK fusion positive lung cancer. Nature medicine, 20(9), 1027-1034.
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5

Preparation and Dissolution of Kinase Inhibitors

Cited 1 time
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X-376 was prepared as described previously14 (link). Crizotinib (ChemieTek, Indianapolis, IN, USA), OSI-906 (Selleck Chemicals, Houston, TX, USA), AEW-541 (Selleck Chemicals, Houston, TX, USA), LDK-378 (Selleck Chemicals, Houston, TX, USA) and Lapatinib (Selleck Chemicals, Houston, TX, USA) were dissolved in DMSO. Erlotinib was synthesized by the Memorial Sloan-Kettering Cancer Center (MSKCC) Organic Synthesis Core. MAb391 (R&D systems, Minneapolis, MN, USA) was dissolved in PBS.
Lovly C.M., McDonald N.T., Chen H., Ortiz-Cuaran S., Heukamp L.C., Yan Y., Florin A., Ozretić L., Lim D., Wang L., Chen Z., Chen X., Lu P., Paik P.K., Shen R., Jin H., Buettner R., Ansén S., Perner S., Brockmann M., Bos M., Wolf J., Gardizi M., Wright G.M., Solomon B., Russell P.A., Rogers T.M., Suehara Y., Red-Brewer M., Tieu R., de Stanchina E., Wang Q., Zhao Z., Johnson D.H., Horn L., Wong K.K., Thomas R.K., Ladanyi M, & Pao W. (2014). Rationale for co-targeting IGF-1R and ALK in ALK fusion positive lung cancer. Nature medicine, 20(9), 1027-1034.
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6

Selective HDAC8 Inhibitors and ALK Inhibitors

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HDAC8-selective inhibitors Cpd2 [13 (link)] (stock concentration 250 mM) and PCI-34051 [14 (link)] (stock 20 mM; Pharmacyclics Inc., Sunnyvale, CA, USA) were dissolved in DMSO. Crizotinib (PF-02341066, stock 10 mM in DMSO, Selleckchem, Houston, USA) and LDK378 (stock 10 mM in DMSO, Selleckchem, Houston, USA) were used as ALK inhibitors. Erlotinib (stock 20 mM; Focus Biomolecules), rapamycin (stock 1 mM; Sigma), LY294002 (stock 10 mM, Cayman) and 20a (Prof. Sippl; University of Halle, Germany) were dissolved in DMSO. EGF stock at 25 µg/ml (PromoKine, Heidelberg, Germany) was also used.
Shen J., Najafi S., Stäble S., Fabian J., Koeneke E., Kolbinger F.R., Wrobel J.K., Meder B., Distel M., Heimburg T., Sippl W., Jung M., Peterziel H., Kranz D., Boutros M., Westermann F., Witt O, & Oehme I. (2018). A kinome-wide RNAi screen identifies ALK as a target to sensitize neuroblastoma cells for HDAC8-inhibitor treatment. Cell Death and Differentiation, 25(12), 2053-2070.
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7

Dissolution of Ceritinib, 5hmdC, and 5fdC

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Ceritinib (a.k.a., LDK378; S7083, Selleckchem, TX), 5hmdC (PY7588, Berry & Associates, MI), and 5fdC (PY7589, Berry & Associates) were dissolved in dimethyl sulfoxide (DMSO; D2650, Sigma–Aldrich, MO). Tetrahydrouridine (584222, Merck Millipore, NJ) was dissolved in water.
Heo H., Kim J.H., Lim H.J., Kim J.H., Kim M., Koh J., Im J.Y., Kim B.K., Won M., Park J.H., Shin Y.J., Yun M.R., Cho B.C., Kim Y.S., Kim S.Y, & Kim M. (2022). DNA methylome and single-cell transcriptome analyses reveal CDA as a potential druggable target for ALK inhibitor–resistant lung cancer therapy. Experimental & Molecular Medicine, 54(8), 1236-1249.
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8

NB Cell Line Authentication and Drug Treatments

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The human NB cell line SK-N-SH and its derivative SH-SY5Y were purchased from the American Type Culture Collection (Manassas, VA, USA) and their authenticity confirmed by genotyping. Cells were also confirmed to be mycoplasma negative. Parental and resistant cells were grown in RPMI media supplemented with 10% fetal bovine serum and 1% penicillin/streptomycin. TAE684 and R428 were synthesized in-house in Dr Nathanael Gray's laboratory (Boston, MA, USA). 17-AAG, CHX and LDK378 were purchased from Selleck Chemicals (Houston, TX, USA), and IPI-504 was purchased from APExBIO (Houston, TX, USA). Recombinant human GAS6 (rGAS6) was purchased from R&D Systems (885-GS-050; Minneapolis, MN, USA).
Debruyne D.N., Bhatnagar N., Sharma B., Luther W., Moore N.F., Cheung N.K., Gray N.S, & George R.E. (2015). ALK inhibitor resistance in ALKF1174L-driven neuroblastoma is associated with AXL activation and induction of EMT. Oncogene, 35(28), 3681-3691.
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9

Inhibitors and Chemotherapeutics for ALK+ Cell Lines

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Crizotinib, NVP-TAE684 and LDK-378 for use in tissue culture studies were purchased from Selleck Chemicals (Houston, TX), dissolved in DMSO and stored at −20C. For in vivo use, Crizotinib was obtained from Aok Bio (Shanghai, China), and NVP-TAE684 and LDK-378 were sourced from MedChemExpress (Monmouth Junction, NJ). The purity of all drugs were greater than 95%, as assessed by LC-MS analysis. ALK inhibitors were suspended in capryol 90 (Gattefosse Corp., Paramus, NJ) for oral gavage of animals. Vincristine (V), actinomycin D (A) and cyclophosphamide (C) were all obtained from the St. Jude pharmacy and were dissolved in sterile saline. They were administered by i.p. injection using a schedule deemed efficacious in pediatric patients (V given weekly at 0.38mg/kg; A given once at 0.5mg/kg; C given once at 125mg/kg).
Antibodies for ALK (31F12 mouse monoclonal, cat# 3791) and G3PDH (D16H11 rabbit HRP-conjugated monoclonal, cat# 8884) were purchased from Cell Signaling (Danvers, MA). siRNA targeting ALK and GFP-tagged RNA used as a control for transfection efficiency were obtained from OriGene (Rockville, MD). The former consists of 3 unique 27mer siRNA duplexes targeting different regions of the ALK mRNA and scrambled siRNA were used as negative controls.
Wierdl M., Tsurkan L., Chi L., Hatfield M.J., Tollemar V., Bradley C., Chen X., Qu C, & Potter P.M. (2018). Targeting ALK in pediatric RMS does not induce antitumor activity in vivo. Cancer chemotherapy and pharmacology, 82(2), 251-263.
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10

Dissolution of Epigenetic Modulators

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Chemicals Ceritinib (a.k.a., LDK378; Selleckchem, S7083), 5hmdC (Berry & Associates, PY7588), and 5fdC (Berry & Associates, PY7589) were dissolved in dimethyl sulfoxide (DMSO, Sigma-Aldrich, D2650). Tetrahydrouridine (Millipore, 584222) was dissolved in water.
Heo H., Kim J., Lim H., Kim J., Kim T.M., Koh J., Im J., Kim B., Won M., Park J.H., Yun M.R., Cho B.C., Kim Y.S., Kim S., & Kim M. (2021). Targeting CDA-Directed Metabolism With 5-Formyl-2'-Deoxycytidine For ALK Inhibitor–Resistant Lung Cancer Therapy.
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