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Updated: Feb 13, 2026

Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development
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Structure-based Design of Pyridone-Aminal eFT508 Targeting Dysregulated Translation by Selective Mitogen-activated

Siegfried H Reich1, Paul A Sprengeler1, Gary G Chiang1

  • 1eFFECTOR Therapeutics , 11180 Roselle Street , San Diego , California 92121 , United States.

Journal of Medicinal Chemistry
|March 13, 2018
PubMed

Insights

Compound 23, a dual mitogen-activated protein kinase (MNK)1/2 inhibitor, shows potent antitumor activity by targeting dysregulated mRNA translation. This novel therapeutic is the first selective dual MNK inhibitor in clinical trials for cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Dysregulated messenger RNA (mRNA) translation is a critical driver of tumorigenesis.
  • Mitogen-activated protein kinase (MNK)1/2 kinases regulate mRNA translation by phosphorylating key proteins like eIF4E, integrating oncogenic and immune signals.
  • Targeting mRNA translation offers a potential therapeutic strategy for cancer by controlling tumor and stromal cell signaling.

Purpose of the Study:

  • To develop and evaluate Compound 23 (eFT508), a selective dual MNK1/2 inhibitor, for its ability to control oncogene signaling at the mRNA translation level.
  • To assess the therapeutic potential of inhibiting MNK1/2 in cancer models.

Main Methods:

  • Structure-guided design of Compound 23, a novel pyridone-aminal dual MNK1/2 inhibitor, utilizing stereoelectronic interactions.
  • In vivo evaluation of Compound 23's antitumor activity in diffuse large B-cell lymphoma and solid tumor models.

Main Results:

  • Compound 23 demonstrated potent in vivo antitumor activity in preclinical models.
  • The compound's design represents a novel pyridone-aminal structure, described for the first time in kinase literature.
  • Compound 23 is the first highly selective dual MNK inhibitor targeting dysregulated translation to enter clinical evaluation.

Conclusions:

  • Inhibiting dysregulated mRNA translation via selective dual MNK1/2 inhibition is a promising therapeutic strategy for cancer.
  • Compound 23 exhibits significant potential and is currently undergoing Phase 2 clinical trials for solid tumors and lymphoma.

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