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pmid:30909944
Deciphering the mechanism of Indirubin and its derivatives in the inhibition of Imatinib resistance using a "drug target prediction-gene microarray analysis-protein network construction" strategy.
Huayao Li · Lijuan Liu · Jing Zhuang · Cun Liu · Chao Zhou · Jing Yang · Chundi Gao · Gongxi Liu · Changgang Sun
BMC complementary and alternative medicine · 2019 doi:10.1186/s12906-019-2471-2
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Complete file
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However, imatinib resistance is currently a clinical problem for CML. It is very importantto find a strategy to inhibit imatinib resistance.\nMETHODS: (1) We Identified indirubin and its derivatives and predicted its putative targets; (2) We downloaded data of the gene chip GSE2810 from the Gene Expression Omnibus (GEO) database and performed GEO2R analysis to obtain differentially expressed genes (DEGs); and (3) we constructed a P-P network of putative targets and DEGs to explore the mechanisms of action and to verify the results of molecular docking.\nRESULT: We Identified a total of 42 small-molecule compounds, of which 15 affected 11 putative targets, indicating the potential to inhibit imatinib resistance; the results of molecular docking verified these results. Six biomarkers of imatinib resistance were characterised by analysing DEGs.\nCONCLUSION: The 15 small molecule compounds inhibited imatinib resistance through the cytokine-cytokine receptor signalling pathway, the JAK-stat pathway, and the NF-KB signalling pathway. 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