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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

Paper

complete

Experiment

complete

Data

partial

Analysis

partial

Execution

absent

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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pmid:30909944
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title
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.
doi
10.1186/s12906-019-2471-2
pmid
30909944
authors array · 9 items
[0]
Huayao Li
[1]
Lijuan Liu
[2]
Jing Zhuang
[3]
Cun Liu
[4]
Chao Zhou
[5]
Jing Yang
[6]
Chundi Gao
[7]
Gongxi Liu
[8]
Changgang Sun
journal
BMC complementary and alternative medicine
year
2019
abstract
BACKGROUND: The 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. RESULT: 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. CONCLUSION: 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. Indirubin and its derivatives may be new drugsthat can combat imatinib resistance.
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The analysis was carried out by using GEO2R, an online analysis tool for the GEO database, based on R language.
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sections[6] "Identify imatinib resistance related genes" paragraph 2
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The analysis was carried out by using GEO2R, an online analysis tool for the GEO database, based on R language.
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Indirubin and 41 derivatives and putative targets
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Indirubin and 41 derivatives and putative targets
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Indirubin and 41 derivatives and putative targets
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Imatinib resistance related genes
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The 62 major targets information of P-P network
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Imatinib resistance related genes
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The 62 major targets information of P-P network
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[3]
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[3]
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Serine-protein kinase ATM
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O60674
[3]
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[1]
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[1]
Amyloid-beta A4 protein
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[3]
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[1]
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[2]
O15111
[3]
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[1]
POU domain, class 5, transcription factor 1
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[1]
G1/S-specific cyclin-D2
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[1]
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P20414
[3]
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[0]
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[1]
Kinesin-like protein KIF11
[2]
P52732
[3]
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[0]
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[1]
Cell division cycle protein 16 homolog
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Q13042
[3]
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[1]
Nitric oxide synthase, brain
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P29475
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[0]
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[1]
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1
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[0]
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[1]
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[1]
E3 ubiquitin-protein ligase XIAP
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[3]
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[1]
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[1]
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WD repeat and FYVE domain-containing protein 2
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[1]
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[1]
D(2) dopamine receptor
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[1]
CASP8 and FADD-like apoptosis regulator
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Cyclin-dependent kinase 3
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[3]
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[1]
Tyrosine-protein phosphatase non-receptor type 2
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P17706
[3]
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[1]
DNA mismatch repair protein Mlh1
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P40692
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[0]
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[1]
Wee1-like protein kinase
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Neural cell adhesion molecule 1
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[1]
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[3]
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[1]
C-X-C motif chemokine 2
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[0]
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[1]
5-hydroxytryptamine receptor 1A
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P08908
[3]
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[0]
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O15105
[3]
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[1]
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[1]
Tyrosine-protein kinase JAK3
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P52333
[3]
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[1]
Interleukin-2 receptor subunit alpha
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P01589
[3]
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[0]
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[1]
Non-receptor tyrosine-protein kinase TYK2
[2]
P29597
[3]
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[0]
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[1]
Dual specificity protein phosphatase CDC14A
[2]
Q9UNH5
[3]
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[59] array · 4 items
[0]
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[1]
Cyclin-dependent kinase 9
[2]
P50750
[3]
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[0]
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[1]
Presenilin-1
[2]
P49768
[3]
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[0]
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[1]
Apolipoprotein B-100
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P04114
[3]
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[0]
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[1]
C-X-C motif chemokine 13
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O43927
[3]
CXCL13
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The docking results of molecule compounds and their putative targets. ‘4 + EGFR’ represents the molecular docking of the indirubin derivative numbered 4 with EGFR, and Score represents the score Identified by molecular docking
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Imatinib resistance related genes
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The docking results of molecule compounds and their putative targets. ‘4 + EGFR’ represents the molecular docking of the indirubin derivative numbered 4 with EGFR, and Score represents the score Identified by molecular docking
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The analysis was carried out by using GEO2R, an online analysis tool for the GEO database, based on R language.
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All data generated or analysed during this study are included in this published article.
basis
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:30909944", "kind": "science-record", "revision": 4, "content_hash": "sha256:f35c6b04c6b4960be836930e1767689b6b46804ce00512027542305ad70eb5b1", "created_at": "2026-11-01T15:40:43Z", "updated_at": "2026-11-01T21:22:05Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "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.", "doi": "10.1186/s12906-019-2471-2", "pmid": "30909944", "authors": ["Huayao Li", "Lijuan Liu", "Jing Zhuang", "Cun Liu", "Chao Zhou", "Jing Yang", "Chundi Gao", "Gongxi Liu", "Changgang Sun"], "journal": "BMC complementary and alternative medicine", "year": 2019, "abstract": "BACKGROUND: The 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.\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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