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

Abstract

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.Electronic supplementary materialThe online version of this article (10.1186/s12906-019-2471-2) contains supplementary material, which is available to authorized users.

Assessing the Anti-inflammatory Effects of Bacopa-Derived Bioactive Compounds Using Network Pharmacology andIn VitroStudies

“…Genes responsible for inflammation were identified through a literature survey. − Furthermore, canonical SMILES of eight selected phytocompounds were employed to find human targets through the SwissTargetPrediction web tool () (Table S1).…”

A Thia-Analogous Indirubin N-Glycoside Disrupts Mitochondrial Function and Causes the Death of Human Melanoma and Cutaneous Squamous Cell Carcinoma Cells

“…Further studies should also include other skin cell lines that show resistance to chemotherapeutic agents. Accordingly, indirubin and its derivatives are currently being discussed to overcome imatinib resistance in CML [75]. Other published data have shown that an indigoid derivative can overcome chemoresistance in leukaemia cells [76] and that I3M sensitises multiple myeloma cells to bortezomib-induced apoptosis and overcomes bortezomib resistance via proteasome inhibition [77].…”

Cryptotanshinone Is a Intervention for ER-Positive Breast Cancer: An Integrated Approach to the Study of Natural Product Intervention Mechanisms

“…The discovery of many drugs is usually driven by the search for new molecular targeted therapies. For complex malignant diseases, single-targeted therapies lack the therapeutic flexibility that makes it difficult to correct the disease state ( Li et al, 2019 ). In this study, by combining high-throughput data analysis with network pharmacology techniques, CPT was initially identified as a multi-target drug that could simultaneously stimulate the characteristics of multiple targets in the disease signaling pathway, providing a novel approach for the clinical treatment of BRCA.…”