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SHR Neuro Krebs Kardio Lipid

Uttarkar, S; Dassé, E; Coulibaly, A; Steinmann, S; Jakobs, A; Schomburg, C; Trentmann, A; Jose, J; Schlenke, P; Berdel, WE; Schmidt, TJ; Müller-Tidow, C; Frampton, J; Klempnauer, KH.
Targeting acute myeloid leukemia with a small molecule inhibitor of the Myb/p300 interaction.
Blood. 2016; 127(9):1173-1182 [OPEN ACCESS]
Web of Science PubMed FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Schlenke Peter
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Abstract:
The transcription factor Myb plays a key role in the hematopoietic system and has been implicated in the development of leukemia and other human cancers. Inhibition of Myb is therefore emerging as a potential therapeutic strategy for these diseases. However, because of a lack of suitable inhibitors, the feasibility of therapeutic approaches based on Myb inhibition has not been explored. We have identified the triterpenoid Celastrol as a potent low-molecular-weight inhibitor of the interaction of Myb with its cooperation partner p300. We demonstrate that Celastrol suppresses the proliferative potential of acute myeloid leukemia (AML) cells while not affecting normal hematopoietic progenitor cells. Furthermore, Celastrol prolongs the survival of mice in a model of an aggressive AML. Overall, our work demonstrates the therapeutic potential of a small molecule inhibitor of the Myb/p300 interaction for the treatment of AML and provides a starting point for the further development of Myb-inhibitory compounds for the treatment of leukemia and, possibly, other tumors driven by deregulated Myb. © 2016 by The American Society of Hematology.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Cell Differentiation - drug effects
Cell Proliferation - drug effects
Chickens -
Disease Models, Animal -
E1A-Associated p300 Protein - metabolism
Gene Expression Regulation, Leukemic - drug effects
HL-60 Cells -
Hematopoietic Stem Cells - drug effects
Hematopoietic Stem Cells - metabolism
Humans -
Leukemia, Myeloid, Acute - drug therapy
Leukemia, Myeloid, Acute - pathology
Mice, Inbred C57BL -
Molecular Targeted Therapy -
Myeloid Cells - drug effects
Myeloid Cells - pathology
Protein Binding - drug effects
Protein Structure, Tertiary -
Proto-Oncogene Proteins c-myb - metabolism
Small Molecule Libraries - pharmacology
Small Molecule Libraries - therapeutic use
Triterpenes - pharmacology
Triterpenes - therapeutic use

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