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A drug–biomarker interaction model to predict the key targets of Scutellaria barbata D. Don in adverse-risk acute myeloid leukaemia

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Abstract

A poor prognosis, relapse and resistance are burning issues during adverse-risk acute myeloid leukaemia (AML) treatment. As a natural medicine, Scutellaria barbata D. Don (SBD) has shown impressive antitumour activity in various cancers. Thus, SBD may become a potential drug in adverse-risk AML treatment. This study aimed to screen the key targets of SBD in adverse-risk AML using the drug–biomarker interaction model through bioinformatics and network pharmacology methods. First, the adverse-risk AML-related critical biomarkers and targets of SBD active ingredient were obtained from The Cancer Genome Atlas database and several pharmacophore matching databases. Next, the protein–protein interaction network was constructed, and topological analysis and pathway enrichment were used to screen key targets and main pathways of intervention of SBD in adverse-risk AML. Finally, molecular docking was implemented for key target verification. The results suggest that luteolin and quercetin are the main active components of SBD against adverse-risk AML, and affected drug resistance, apoptosis, immune regulation and angiogenesis through the core targets AKT1, MAPK1, IL6, EGFR, SRC, VEGFA and TP53. We hope the proposed drug–biomarker interaction model provides an effective strategy for the research and development of antitumour drugs.

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The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

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Funding

This research is funded by the following projects: National Natural Science Foundation of China (No. 81473511 and 81974547).

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R.X., C.L. and T.W. were involved in conceptualization and methodology; T.W. and C.L. contributed to software; Y.J., X.D. and Y.W. helped in validation; X.D., J.W. and Z.L. helped in data curation; T.W. was involved in original draft writing; Y.J., T.W. and R.X. helped in review and editing; T.W. and C.L. were involved in visualization; X.D., Y.J. and Z.L. were involved in supervision; R.X. and Y.W. helped in funding acquisition. All authors have read and approved the final manuscript.

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Correspondence to Rui-rong Xu.

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Wang, T., Lyu, Cy., Jiang, Yh. et al. A drug–biomarker interaction model to predict the key targets of Scutellaria barbata D. Don in adverse-risk acute myeloid leukaemia. Mol Divers 25, 2351–2365 (2021). https://doi.org/10.1007/s11030-020-10124-z

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