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• W3107745265 abstract "Dasatinib is a multi-target kinase inhibitor, whose targets include BCR-ABL, SRC family kinases, and various cancer kinases. The elevated SRC activity in gastric cancer (GC) has prompted the need for the therapeutic application of dasatinib in GC. We observed that the efficacy of dasatinib varied with the GC cell lines. The differential effect of dasatinib was not correlated with the basal SRC activity of each cell line. Moreover, the GC cell lines showing the strong antitumor effects of dasatinib were refractory to other SRC inhibitors, i.e., bosutinib and saracatinib, suggesting that unexpected dasatinib’s targets could exist. To profile the targets of dasatinib in GC, we performed activity-based protein profiling (ABPP) via mass spectrometry using a desthiobiotin-ATP probe. We identified 29 and 18 kinases as potential targets in dasatinib-sensitive (SNU-216, MKN-1) and -resistant (SNU-484, SNU-601) cell lines, respectively. The protein–protein interaction mapping of the differential drug targets in dasatinib-sensitive and -resistant GC using the STRING database suggested that dasatinib could target cellular energy homeostasis in the drug-sensitive GC. RNAi screening for identified targets indicated p90RSK could be a novel dasatinib target, which is important for maintaining the viability and motility of GC cells. Further functional validation of dasatinib off-target actions will provide more effective therapeutic options for GC." @default.
• W3107745265 created "2020-12-07" @default.
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• W3107745265 date "2020-12-04" @default.
• W3107745265 modified "2023-09-26" @default.
• W3107745265 title "Activity-Based Protein Profiling Reveals Potential Dasatinib Targets in Gastric Cancer" @default.
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• W3107745265 doi "https://doi.org/10.3390/ijms21239276" @default.
• W3107745265 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7729964" @default.
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