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
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
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以“药靶预测-基因芯片分析-蛋白网络构建”策略解读靛玉红及其衍生物抑制伊马替尼耐药的机制
DOI：
10.1186/s12906-019-2471-2
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发表时间：
2019-03-25
影响因子：
--
通讯作者：
Sun, Changgang
中科院分区：
文献类型：
--
作者：
Li, Huayao;Liu, Lijuan;Sun, Changgang
BackgroundThe introduction of imatinib revolutionized the treatment of chronic myeloid leukaemia (CML), substantially extending patient survival. However, imatinib resistance is currently a clinical problem for CML. It is very importantto find a strategy to inhibit imatinib resistance.Methods(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.ResultWe 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.ConclusionThe 15 small molecule compounds inhibited imatinib resistance through the cytokine-cytokine receptor signalling pathway, the JAK-stat pathway, and the NF-KB signalling pathway. Indirubin and its derivatives may be new drugsthat can combat imatinib resistance.
