Vandetanib

Manufactured by Selleck Chemicals

Sourced in United States, Germany

Vandetanib is a synthetic compound used in research and development applications. It functions as a tyrosine kinase inhibitor, capable of inhibiting the activity of certain enzymes involved in cellular processes. This product is intended for laboratory use only and its specific applications may vary depending on the research objectives.

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Lab products found in correlation

20 protocols using vandetanib

Vandetanib Inhibits RET Mutant-Driven Signaling

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The primary antibodies used in this study included anti-phospho-RET (Tyr905, #3221), anti-RET (#14556), anti-phospho-ERK (Thr202/Tyr204, #9101S), anti-ERK (#9102), anti-phospho-AKT (Ser473, #9271) and anti-AKT (#9272). They were purchased from Cell Signaling Technology. Anti-GAPDH (# G8795) was purchased from sigma.
Vandetanib was purchased from Selleck Chemicals and diluted with DMSO to 6 concentrations: 0, 500, 750, 1000, 2000, and 5000 nM. For Vandetanib inhibition test, A2780 cells transfected with RET mutants were cultured with different concentrations of Vandetanib for 72 h. For western blotting, A2780 cells transfected with EV, WT or RET mutants were treated with 500 nM Vandetanib for 4 h before harvesting.

Guan L., Li Z., Xie F., Pang Y., Zhang C., Tang H., Zhang H., Chen C., Zhan Y., Zhao T., Jiang H., Jia X., Wang Y, & Lu Y. (2020). Oncogenic and drug-sensitive RET mutations in human epithelial ovarian cancer. Journal of Experimental & Clinical Cancer Research : CR, 39, 53.

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RET Fusion Cancer Cell Line Maintenance

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The mesothelioma cell line EHMES-10 [17 (link)–19 (link)] containing a NCOA4-RET fusion, and human lung adenocarcinoma cell line LC-2/ad [20 (link)] and thyroid papillary carcinoma cell line TPC-1 [21 (link)] containing a CCDC6-RET fusion were used in this study. All cells were maintained in RPMI-1640 medium supplemented with 10% FBS, penicillin (100 U/mL), and streptomycin (10 μg/mL) in a humidified CO₂ incubator at 37°C. All cells were passaged for less than 3 months before renewal from frozen early-passage stocks. Cells were regularly screened for mycoplasma using a MycoAlert Mycoplasma Detection Kit (Lonza, Rockland, ME, USA). Alectinib, vandetanib, and lenvatinib were obtained from Selleck Chemicals (Houston, TX, USA).

Arai S., Kita K., Tanimoto A., Takeuchi S., Fukuda K., Sato H, & Yano S. (2017). In vitro and in vivo anti-tumor activity of alectinib in tumor cells with NCOA4-RET. Oncotarget, 8(43), 73766-73773.

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Cytotoxicity Assay of Oncology Drugs

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AD80, BLU-667, cabozantinib, and vandetanib were all obtained from Selleckchem LOXO-292 was obtained from MedChemExpress and all drugs were resuspended in DMSO. Cells were treated with drug for 72 hours prior to the WST assay and viability was measured using the WST reagent (Takara) following manufacturer’s protocol. Each concentration data point was conducted in triplicate. Each compound was tested at a minimum of ten dose levels, separated by four-fold dilution concentration intervals, LD₅₀ values were calculated using GraphPad Prism 7. Reported values were calculated from a single WST assay, but were confirmed by repeating the entire assay in duplicate.

VanDeusen H.R., Ramroop J.R., Morel K.L., Bae S.Y., Sheahan A.V., Sychev Z., Lau N.A., Cheng L.C., Tan V.M., Li Z., Petersen A., Lee J.K., Park J.W., Yang R., Hwang J.H., Coleman I., Witte O.N., Morrissey C., Corey E., Nelson P.S., Ellis L, & Drake J.M. (2020). Targeting RET Kinase in Neuroendocrine Prostate Cancer. Molecular cancer research : MCR, 18(8), 1176-1188.

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Anti-EGFR TKI Sensitization in Tumor Cells

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For anti-EGFR sensitization, the IGORV-1 and SKOV-3 tumor cells were cultured in RPMI-1640 supplemented with 10% FCS, 100 units/mL penicillin, and 100 µg/mL streptomycin. The anti-EGFR tyrosine kinase inhibitors (TKIs) erlotinib, gefitinib, and vandetanib (all from Selleck Chemicals, Houston, TX, USA) were reconstituted in DMSO (dimethyl sulfoxide, Carl-Roth-GmbH, Karlsruhe, Germany) before use. They were added to the culture in RPMI-1640 in a concentration of 1 µM which was titrated previously [24 (link)]. Cells were passaged and cultured continuously under anti-EGFR TKI treatment for 7 days and 6 weeks, respectively.

Mallmann-Gottschalk N., Sax Y., Kimmig R., Lang S, & Brandau S. (2019). EGFR-Specific Tyrosine Kinase Inhibitor Modifies NK Cell-Mediated Antitumoral Activity against Ovarian Cancer Cells. International Journal of Molecular Sciences, 20(19), 4693.

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Vandetanib treatment in vitro and in vivo

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For in vitro experiments, vandetanib (SelleckChem: Germany) was used at a final concentration of 10 μM and was added 72 hours after transfection with siRNA for 24 hours of drug treatment. For animal experiments, vandetanib stock was initially dissolved in DMSO and then water to a final concentration of (10 μM) and administered by oral gavage at 10 mg/kg. Parallel experiments with corresponding concentrations of DMSO in water were used as a vehicle control gavage.

De Andrade J.P., Park J.M., Gu V.W., Woodfield G.W., Kulak M.V., Lorenzen A.W., Wu V.T., Van Dorin S.E., Spanheimer P.M, & Weigel R.J. (2016). EGFR Is Regulated by TFAP2C in Luminal Breast Cancer and Is a Target for Vandetanib. Molecular cancer therapeutics, 15(3), 503-511.

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Optimizing Compound Solubilization and Dilution

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Sunitinib malate (SU-11248; see Chow and Eckhardt, 2007 for chemical structure)15 (link) and temozolomide were purchased from Sigma-Aldrich (Taufkirchen, Germany). For ex vivo and in vitro assays, sunitinib was solubilized in sterile water to a dilution concentration of 10 mM. temozolomide was dissolved in DMSO at 300 mM and working concentrations were prepared with PBS. Imatinib, orantinib (SU6668), vandetanib, and wortmannin were purchased from Selleck Chemicals (Selleckchem, Munich, Germany), bryostatin and SU1498 were from Merck (Darmstadt, Germany), and salirasib was purchased from Cayman Chemical Company (Ann Arbor, MI, USA). All inhibitors were diluted under sterile conditions with DMSO to a suggested dilution concentration of 100 mM. The final working solutions had a maximal DMSO concentration of 0.2%.

Hatipoglu G., Hock S.W., Weiss R., Fan Z., Sehm T., Ghoochani A., Buchfelder M., Savaskan N.E, & Eyüpoglu I.Y. (2015). Sunitinib impedes brain tumor progression and reduces tumor-induced neurodegeneration in the microenvironment. Cancer Science, 106(2), 160-170.

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Vandetanib Dissolution and Preparation

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Vandetanib (ZD6474) was purchased from Selleck Chemicals (Houston, TX, USA). All chemicals for solution preparation were purchased from Sigma-Aldrich Co. (Sigma-Aldrich, St. Louis, MO, USA).

Lee H.A., Hyun S.A., Byun B., Chae J.H, & Kim K.S. (2018). Electrophysiological mechanisms of vandetanib-induced cardiotoxicity: Comparison of action potentials in rabbit Purkinje fibers and pluripotent stem cell-derived cardiomyocytes. PLoS ONE, 13(4), e0195577.

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Synthesis and Evaluation of NMS-P645

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NMS-P645 was synthesized by Nerviano Medical Sciences as described 21 (link). GDC-0941 and vandetanib were purchased from Selleck Chemicals. Taxol was from Sigma Aldrich (Merck group, Germany). All compounds were dissolved at the desired concentration following manufacturer's guidelines.

Mologni L., Magistroni V., Casuscelli F., Montemartini M, & Gambacorti-Passerini C. (2017). The Novel PIM1 Inhibitor NMS-P645 Reverses PIM1-Dependent Effects on TMPRSS2/ERG Positive Prostate Cancer Cells And Shows Anti-Proliferative Activity in Combination with PI3K Inhibition. Journal of Cancer, 8(1), 140-145.

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Multidrug-resistant Oral Cancer Cell Lines

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Rhodamine123 (Rhodamine) and verapamil were purchased from Sigma-Aldrich (St. Louis, MO, USA). VIC was purchased from Enzo Life Sciences (Farmingdale, NY, USA). Gefitinib, imatinib, erlotinib, nilotinib, pazopanib, masatinib, sunitinib, sorafenib, regorafenib, lapatinib, vandetanib, cediranib, and crizotinib were purchased from Selleckchem (Houston, TX, USA). For in vivo xenograft experiments, VIC was purchased from APExBIO technology (TX, USA) and crizotinib was purchased from MedChemExpress (NJ, USA). Aqueous solutions of eribulin (Eisai Korea, Seoul, South Korea) were obtained from the National Cancer Center in South Korea.
Human oral squamous carcinoma cell line, parent sensitive KB, and its multidrug-resistant subline, KBV20C, were obtained from Dr. Yong Kee Kim (College of Pharmacy, Sookmyung Women's University, Seoul, South Korea) and have been previously described (12 (link), 29 (link)–31 (link)). All cell lines were cultured in RPMI 1640 containing 10% fetal bovine serum, 100 U/ml penicillin, and 100 μg/ml streptomycin (WelGENE, Daegu, South Korea).

Kim K.S., Jiang C., Kim J.Y., Park J.H., Kim H.R., Lee S.H., Kim H.S, & Yoon S. (2020). Low-Dose Crizotinib, a Tyrosine Kinase Inhibitor, Highly and Specifically Sensitizes P-Glycoprotein-Overexpressing Chemoresistant Cancer Cells Through Induction of Late Apoptosis in vivo and in vitro. Frontiers in Oncology, 10, 696.

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Modulation of MDSC Function in Mice

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Bone marrow cells were obtained from the femurs and tibias of 8-week-old female C57BL/6 mice and cultured in six-well plates in RPMI 1640 medium containing 10% FBS. The medium was supplemented with 40 ng/mL GM-CSF (PeproTech, AF-315-03,), GM-CSF + 40 ng/mL IL-6 (PeproTech, 216-16-100) or GM-CSF + GXM (10 μg/well). Vandetanib (Selleck, ZD6474) was added at a final concentration of 2 μM in the drug treatment group, and DMSO was used for the control group. 5 days later, the cells were harvested, and the proportion and suppressive function of MDSCs were analyzed using flow cytometry.

Li Y.N., Wang Z.W., Li F., Zhou L.H., Jiang Y.S., Yu Y., Ma H.H., Zhu L.P., Qu J.M, & Jia X.M. (2022). Inhibition of myeloid-derived suppressor cell arginase-1 production enhances T-cell-based immunotherapy against Cryptococcus neoformans infection. Nature Communications, 13, 4074.

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