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Modulation of ERK5 Activity as a Therapeutic Anti-Cancer Strategy

Lookup NU author(s): Duncan MillerORCiD, Dr Suzannah HarnorORCiD, Dr Mathew Martin, Dr Richard NobleORCiD, Professor Steve Wedge, Dr Celine CanoORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2023 The Authors. Published by American Chemical Society. The extracellular signal-regulated kinase 5 (ERK5) signaling pathway is one of four conventional mitogen-activated protein (MAP) kinase pathways. Genetic perturbation of ERK5 has suggested that modulation of ERK5 activity may have therapeutic potential in cancer chemotherapy. This Miniperspective examines the evidence for ERK5 as a drug target in cancer, the structure of ERK5, and the evolution of structurally distinct chemotypes of ERK5 kinase domain inhibitors. The emerging complexities of ERK5 pharmacology are discussed, including the confounding phenomenon of paradoxical ERK5 activation by small-molecule ERK5 inhibitors. 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.

Publication metadata

Author(s): Miller DC, Harnor SJ, Martin MP, Noble RA, Wedge SR, Cano C

Publication type: Review

Publication status: Published

Journal: Journal of Medicinal Chemistry

Year: 2023

Volume: 66

Issue: 7

Pages: 4491-4502

Print publication date: 13/04/2023

Online publication date: 01/04/2023

Acceptance date: 02/04/2018

ISSN (print): 0022-2623

ISSN (electronic): 1520-4804

Publisher: American Chemical Society


DOI: 10.1021/acs.jmedchem.3c00072

PubMed id: 37002872