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Updated: Sep 27, 2025
13:22
Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays
Published on: October 23, 2019
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Src-Family Protein Kinase Inhibitors Suppress MYB Activity in a p300-Dependent Manner
Abhiruchi Biyanee1, Maria V Yusenko1, Karl-Heinz Klempnauer1
1Institute for Biochemistry, Westfälische-Wilhelms-Universität, D-48149 Münster, Germany.
Cells
|April 12, 2022
Summary
Protein kinase inhibitors bosutinib, PD180970, and PD161570 show MYB inhibitory activity. These drugs may offer new treatments for acute myeloid leukemia (AML) by targeting MYB function.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Transcription factor MYB is a key driver in malignancies like acute myeloid leukemia (AML).
- Targeting transcription factors like MYB has been challenging, but recent successes with small molecules are promising.
- Repurposing existing drugs offers a faster route to novel cancer therapies.
Purpose of the Study:
- To identify existing drugs with MYB-inhibitory potential for cancer treatment.
- To investigate the mechanism of MYB inhibition by identified compounds.
- To evaluate the therapeutic effects of MYB inhibitors in AML models.
Main Methods:
- Screening of approved drugs and drug-like compounds for MYB inhibitory activity.
- Assessing the impact of compounds on MYB transactivation domain and p300 coactivator interaction.
- Treating acute myeloid leukemia (AML) cell line HL60 with identified compounds.
- Analyzing myeloid differentiation marker CD11b expression and cell death induction.
- Validating MYB inhibition relevance using forced expression of activated MYB.
Main Results:
- Identified bosutinib, PD180970, and PD161570 as MYB-inhibitory agents.
- Demonstrated that these compounds disrupt MYB cooperation with the p300 coactivator.
- Observed induction of CD11b expression and cell death in HL60 cells.
- Confirmed that MYB inhibition is responsible for the observed anti-leukemic effects.
Conclusions:
- Protein kinase inhibitors bosutinib, PD180970, and PD161570 are novel MYB inhibitors.
- MYB inhibition by these compounds has a relevant pharmacological impact on leukemic cells.
- These findings suggest a potential therapeutic strategy for MYB-dependent cancers.
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