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Preclinical development consists of a series of tests that ensure the safety and efficacy of a new therapeutic compound before it is tested in humans. There are four main phases to this process. First, safety pharmacology tests are conducted to ensure the drug does not produce any acutely harmful effects. These tests examine parameters such as bronchoconstriction, cardiac dysrhythmias, blood pressure changes, and ataxia. Next, preliminary toxicological testing is performed to determine the...

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Updated: Nov 8, 2025

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway

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Published on: August 23, 2024

Progress in developing MNK inhibitors.

Xin Jin¹, Rilei Yu², Xuemin Wang³

¹School of Medicine and Pharmacy, Ocean University of China and Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China; College of Marine Life Sciences, Ocean University of China, Qingdao, China.

European Journal of Medicinal Chemistry

|April 23, 2021

Summary

This summary is machine-generated.

Mitogen-activated protein kinase-interacting protein kinases (MNKs) regulate protein translation crucial for cancer. MNK inhibitors show promise as safe cancer treatments, with several in clinical trials.

Keywords:

Antitumor activity MNK Protein kinase inhibitors eIF4E

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Area of Science:

Biochemistry and Molecular Biology
Oncology
Pharmacology

Background:

Mitogen-activated protein kinase-interacting protein kinases (MNKs) phosphorylate eukaryotic initiation factor 4E (eIF4E) at serine 209.
Phosphorylation of eIF4E by MNKs is implicated in mRNA translation, tumor development, cell migration, invasion, and energy metabolism.
Elevated MNK and eIF4E levels are observed in various cancers, including solid tumors and leukemia, and also in metabolic diseases.

Purpose of the Study:

To review diverse MNK inhibitors reported in scientific literature and patents.
To summarize their in vitro and in vivo activities.
To highlight the therapeutic potential of MNK inhibition in cancer and metabolic diseases.

Main Methods:

Literature and patent review of MNK inhibitors.
Analysis of reported in vitro and in vivo efficacy data.
Summary of inhibitor development from broad-spectrum to selective MNK1/2 inhibitors.

Main Results:

Several MNK inhibitors and 'degraders' have been identified and developed.
Early inhibitors were often multi-kinase inhibitors; later compounds show increased potency and selectivity for MNK1/2.
Three inhibitors (BAY1143269, eFT508, ETC-206) are in clinical trials for various cancers.

Conclusions:

MNK pathways are critical regulators in cancer and metabolic disease.
MNK inhibition represents a potentially safe and effective therapeutic strategy.
Ongoing clinical trials will further elucidate the efficacy of MNK inhibitors in cancer treatment.