Medicinal chemistry approaches to target the MNK-eIF4E axis in cancer

Ann Fernandez, Paige J. Monsen, Leonidas C. Platanias, Gary E. Schiltz*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

3 Scopus citations


Aberrant translation of proteins that promote cell proliferation is an essential factor that defines oncogenic processes and cancer. The process for ribosomal translation of proteins from mRNA requires an essential initiation step which is controlled by the protein eIF4E, which binds the RNA 5′-cap and forms the eIF4F complex that subsequently translates protein. Typically, eIF4E is activated by phosphorylation on Ser209 by MNK1 and MNK2 kinases. Substantial work has shown that eIF4E and MNK1/2 are dysregulated in many cancers and this axis has therefore become an active area of interest for developing new cancer therapeutics. This review summarizes and discusses recent work to develop small molecules that target different steps in the MNK-eIF4E axis as potential cancer therapeutics. The aim of this review is to cover the breadth of different molecular approaches being taken and the medicinal chemistry basis for their optimization and testing as new cancer therapeutics.

Original languageEnglish (US)
Pages (from-to)1060-1087
Number of pages28
JournalRSC Medicinal Chemistry
Issue number6
StatePublished - May 9 2023

ASJC Scopus subject areas

  • Drug Discovery
  • Molecular Medicine
  • Biochemistry
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry


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