jm7b00369_si_001.csv (1.98 kB)
Download fileNew Inhibitor Targeting Signal Transducer and Activator of Transcription 5 (STAT5) Signaling in Myeloid Leukemias
dataset
posted on 2017-06-27, 00:00 authored by Ludovic Juen, Marie Brachet-Botineau, Cécile Parmenon, Jérôme Bourgeais, Olivier Hérault, Fabrice Gouilleux, Marie-Claude Viaud-Massuard, Gildas PriéSignal transducers
and activators of transcription 5 (STAT5s) are
crucial effectors of tyrosine kinase oncogenes in myeloid leukemias.
Inhibition of STAT5 would contribute to reducing the survival of leukemic
cells and also tackling their chemoresistance. In a first screening
experiment, we identified hit 13 as able to inhibit STAT5
phosphorylation and leukemic cell growth. The synthesis of 18 analogues
of 13 allowed us to identify one compound, 17f, as having the most potent antileukemic effect. 17f inhibited the growth of acute and chronic myeloid leukemia cells
and the phosphorylation and transcriptional activity of STAT5. Importantly, 17f had minimal effects on bone marrow stromal cells that
play vital functions in the microenvironment of hematopoietic and
leukemic cells. We also demonstrated that 17f inhibits
STAT5 but not STAT3, AKT, or Erk1/2 phosphorylation. These results
suggest that 17f might be a new lead molecule targeting
STAT5 signaling in myeloid leukemias.