New Perspective Article – Therapeutic potential of ERK5 inhibitors

J. Med. Chem. 2023, 66, 4491-4502

https://doi.org/10.1021/acs.jmedchem.3c00072

https://pubs.acs.org/doi/full/10.1021/acs.jmedchem.3c00072

Duncan C. Miller, Suzannah J. Harnor, Mathew P. Martin, Richard A. Noble, Stephen R. Wedge and Celine Cano*

The extracellular signal-regulated kinase 5 (ERK5) signalling pathway is one of four conventional mitogen-activated protein (MAP) kinase pathways. MAP kinases are central to several pathologies, including cancer, with genetic perturbation of ERK5 suggesting that modulation of ERK5 activity may have therapeutic potential.

This Miniperspective examines and discusses the structure and function of ERK5, the medicinal chemistry progress that has been made in inhibiting ERK5 kinase activity with small molecules, the pharmacological outcomes resulting from chemical-induced ERK5 degradation, and the collective implications for ERK5 modulation as an anti-cancer therapeutic strategy.  The impact of the recent development and biological evaluation of potent and selective bifunctional degraders of ERK5, and future opportunities in ERK modulation are also explored.  

Last modified: Wed, 19 Apr 2023 07:44:44 BST