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Oncotarget

Oncotarget

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Inhibitory effects of Tomivosertib in acute myeloid leukemia

Published:11 May 2021 DOI: 10.18632/oncotarget.27952 PMID: 34012509
Milagros Suarez, Gavin T Blyth, Alain A Mina, Ewa M Kosciuczuk, Blazej Dolniak, Shira Dinner, Jessica K Altman, Elizabeth A Eklund, Diana Saleiro, Elspeth M Beauchamp, Leonidas C Platanias

Abstract

The MAPK-interacting kinases 1 and 2 (MNK1/2) have generated increasing interest as therapeutic targets for acute myeloid leukemia (AML). We evaluated the therapeutic potential of the highly-selective MNK1/2 inhibitor Tomivosertib on AML cells. Tomivosertib was highly effective at blocking eIF4E phosphorylation on serine 209 in AML cells. Such inhibitory effects correlated with dose-dependent suppression of cellular viability and leukemic progenitor colony formation. Moreover, combination of Tomivosertib and Venetoclax resulted in synergistic anti-leukemic responses in AML cell lines. Mass spectrometry studies identified novel putative MNK1/2 interactors, while in parallel studies we demonstrated that MNK2 - RAPTOR - mTOR complexes are not disrupted by Tomivosertib. Overall, these findings demonstrate that Tomivosertib exhibits potent anti-leukemic properties on AML cells and support the development of clinical translational efforts involving the use of this drug, alone or in combination with other therapies for the treatment of AML.

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Materials Related products
Procduct Name CAS Molecular Formula Supplier Price
ABT-199 1257044-40-8 C45H50ClN7O7S 534 suppliers $12.00-$4766.80
ABT-199 1257044-40-8 C45H50ClN7O7S 534 suppliers $12.00-$4766.80
ABT-199 1257044-40-8 C45H50ClN7O7S 534 suppliers $12.00-$4766.80
ABT-199 1257044-40-8 C45H50ClN7O7S 534 suppliers $12.00-$4766.80
EFT-508 1849590-01-7 C17H20N6O2 101 suppliers $28.00-$4741.00
EFT-508 1849590-01-7 C17H20N6O2 101 suppliers $28.00-$4741.00
EFT-508 1849590-01-7 C17H20N6O2 101 suppliers $28.00-$4741.00
EFT-508 1849590-01-7 C17H20N6O2 101 suppliers $28.00-$4741.00
ABT-199 1257044-40-8 - Inquiry
ABT-199 1257044-40-8 - Inquiry

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