Thursday, July 11, 2013
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MAP kinase interacting serine-threonine kinase 1 (MKNK1;
translation initiation factor 4E (eIF4E)
In vitro and mouse studies suggest inhibiting MNK1 and MNK2
could help treat the blast crisis phase of CML by reducing eIF4E activation.
Self-renewal of granulocyte macrophage progenitors (GMPs) is associated with
blast crisis. In GMPs from patients with CML, MNK1 and MNK2 inhibition
decreased eIF4E activation and self-renewal capacity compared with no
inhibition. In xenograft mouse models for CML blast crisis, an MNK1 and MNK2
inhibitor decreased GMP engraftment compared with vehicle. Ongoing work
includes testing dual MNK and BCR-ABL
tyrosine kinase inhibitors in cellular and animal models
Pharmaceuticals Inc.'s ISIS-EIF4ERx,
a second-generation antisense oligonucleotide targeting eIF4E, is in Phase
I/II testing to treat non-small cell lung cancer (NSCLC) and prostate cancer.
Clavis Pharma ASA and Translational
Therapeutics Inc. have ribavirin
a Lipid Vector Technology derivative of ribavirin that inhibits eIF4E, in
preclinical testing to treat thyroid cancer.
Published online July 11, 2013
Unpatented; available for
Lim, S. et al. Proc.
Natl. Acad. Sci. USA; published online June 4, 2013;
Contact: S. Tiong Ong, Duke-NUS Graduate Medical School Singapore,
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