ReviewBiochemical Society transactions2020
Small molecule ERK5 kinase inhibitors paradoxically activate ERK5 signalling: be careful what you wish for….
Review in Biochemical Society transactions, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- Development of a chaperone-mediated protein degrader targeting ERK5 that efficaciously reduces tumor growth.Cell communication and signaling : CCS · 2026Article
- VCAN Is Essential for ERK5-Driven Tumorigenesis in Soft Tissue Sarcoma.International journal of biological sciences · 2026Article
- The Discovery of Small ERK5 Inhibitors via Structure-Based Virtual Screening, Biological Evaluation and MD Simulations.Molecules (Basel, Switzerland) · 2025Article
- Anti-cancer Effects of 1,4-Dialkoxynaphthalene-Imidazolium Salt Derivatives through ERK5 kinase activity inhibition.Scientific reports · 2025Article
- Is the MAPK ERK5 the nexus from FAO to NK cell-mediated metastasis immune surveillance?Frontiers in immunology · 2025Review
- Enzyme Is the Name-Adapter Is the Game.Cells · 2024Review
- Identification of a Novel ERK5 (MAPK7) Inhibitor, MHJ-627, and Verification of Its Potent Anticancer Efficacy in Cervical Cancer HeLa Cells.Current issues in molecular biology · 2023Article
- Medicinal chemistry approaches to target the MNK-eIF4E axis in cancer.RSC medicinal chemistry · 2023Review
- Modulation of ERK5 Activity as a Therapeutic Anti-Cancer Strategy.Journal of medicinal chemistry · 2023Review
- The significance of ERK5 catalytic-independent functions in disease pathways.Frontiers in cell and developmental biology · 2023Review
- Premature senescence and cardiovascular disease following cancer treatments: mechanistic insights.Frontiers in cardiovascular medicine · 2023Review
- OXTRNature communications · 2022Article
- Parallel Optimization of Potency and Pharmacokinetics Leading to the Discovery of a Pyrrole Carboxamide ERK5 Kinase Domain Inhibitor.Journal of medicinal chemistry · 2022Article
- Overcoming Paradoxical Kinase Priming by a Novel MNK1 Inhibitor.Journal of medicinal chemistry · 2022Article
- The pleiotropic roles of circular and long noncoding RNAs in cutaneous melanoma.Molecular oncology · 2022Review
- ERK5 Signalling and Resistance to ERK1/2 Pathway Therapeutics: The Path Less Travelled?Frontiers in cell and developmental biology · 2022Review
- The MEK5/ERK5 Pathway in Health and Disease.International journal of molecular sciences · 2021Review
- Identification and Validation of ERK5 as a DNA Damage Modulating Drug Target in Glioblastoma.Cancers · 2021Article
- The Investigation ofIn vivo (Athens, Greece)Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
ERK5 is a protein kinase that also contains a nuclear localisation signal and a transcriptional transactivation domain. Inhibition of ERK5 has therapeutic potential in cancer and inflammation and this has prompted the development of ERK5 kinase inhibitors (ERK5i). However, few ERK5i programmes have taken account of the ERK5 transactivation domain. We have recently shown that the binding of small molecule ERK5i to the ERK5 kinase domain stimulates nuclear localisation and paradoxical activation of its transactivation domain. Other kinase inhibitors paradoxically activate their intended kinase target, in some cases leading to severe physiological consequences highlighting the importance of mitigating these effects. Here, we review the assays used to monitor ERK5 activities (kinase and transcriptional) in cells, the challenges faced in development of small molecule inhibitors to the ERK5 pathway, and classify the molecular mechanisms of paradoxical activation of protein kinases by kinase inhibitors.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.