Bcr-TMP, a Novel Nanomolar-Active Compound That Exhibits Both MYB- and Microtubule-Inhibitory Activity
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Cells
2.2. Library Screening and Compounds
2.3. Expression Vectors and Transfections
2.4. Electrophoretic Mobility Shift Assays (EMSA)
2.5. Quantitative Real-Time PCR
2.6. Flow Cytometry
2.7. Proliferation and Apoptosis Assays
2.8. Western Blotting
2.9. Tubulin Polymerization Assay
2.10. Immunofluorescence Staining of Actin and Tubulin Cytoskeleton
2.11. Statistical Analysis
3. Results
3.1. Identification of Bcr-TMP as a Highly Active MYB-Inhibitory Compound
3.2. Bcr-TMP Decreases the Activity of the MYB Transactivation Domain
3.3. Bcr-TMP Induces the Expression of Myeloid Differentiation Markers and Cell Death in AML Cell Lines
3.4. Bcr-TMP Targets a MYB-C/EBPβ-p300 Transcriptional Module
3.5. Bcr-TMP Suppresses the Proliferation of Murine MLL-AF9 Transformed AML Cells and of Patient-Derived ACC Cells
3.6. Bcr-TMP Exhibits Microtubule-Destabilizing Activity
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Yusenko, M.V.; Biyanee, A.; Frank, D.; Köhler, L.H.F.; Andersson, M.K.; Khandanpour, C.; Schobert, R.; Stenman, G.; Biersack, B.; Klempnauer, K.-H. Bcr-TMP, a Novel Nanomolar-Active Compound That Exhibits Both MYB- and Microtubule-Inhibitory Activity. Cancers 2022, 14, 43. https://doi.org/10.3390/cancers14010043
Yusenko MV, Biyanee A, Frank D, Köhler LHF, Andersson MK, Khandanpour C, Schobert R, Stenman G, Biersack B, Klempnauer K-H. Bcr-TMP, a Novel Nanomolar-Active Compound That Exhibits Both MYB- and Microtubule-Inhibitory Activity. Cancers. 2022; 14(1):43. https://doi.org/10.3390/cancers14010043
Chicago/Turabian StyleYusenko, Maria V., Abhiruchi Biyanee, Daria Frank, Leonhard H. F. Köhler, Mattias K. Andersson, Cyrus Khandanpour, Rainer Schobert, Göran Stenman, Bernhard Biersack, and Karl-Heinz Klempnauer. 2022. "Bcr-TMP, a Novel Nanomolar-Active Compound That Exhibits Both MYB- and Microtubule-Inhibitory Activity" Cancers 14, no. 1: 43. https://doi.org/10.3390/cancers14010043