ArticleNature communications2018
Dimethyl fumarate is an allosteric covalent inhibitor of the p90 ribosomal S6 kinases.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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.
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Who cites it
21 citing papers in PubMed, 37 citations in OpenAlex.
- Fumarate and Its Esters: Physiology, Pathology, Molecular Mechanisms, Diseases, and Therapy.MedComm · 2026Review
- Itaconation and Succination as Metabolite-Derived Cysteine Modifications in Inflammatory Signalling: Biochemical Mechanisms, Chemoproteomic Mapping, and Therapeutic Opportunities.Cell biochemistry and biophysics · 2026Review
- Dimethyl Fumarate vs. Monomethyl Fumarate: Unresolved Pharmacologic Issues.Pharmaceutics · 2025Review
- Proteome-wide ligandability maps of drugs with diverse cysteine-reactive chemotypes.Nature communications · 2025Article
- Nrf2-Independent Anti-Inflammatory Effects of Dimethyl Fumarate: Challenges and Prospects in Developing Electrophilic Nrf2 Activators for Neurodegenerative Diseases.Antioxidants (Basel, Switzerland) · 2024Review
- Integrated Covalent Drug Design Workflow Using Site Identification by Ligand Competitive Saturation.Journal of chemical theory and computation · 2023Article
- Activation and inhibition of the C-terminal kinase domain of p90 ribosomal S6 kinases.Life science alliance · 2023Article
- Review
- Therapeutic targeting of p90 ribosomal S6 kinase.Frontiers in cell and developmental biology · 2023Review
- MiR-142-3p regulates synaptopathy-driven disease progression in multiple sclerosis.Neuropathology and applied neurobiology · 2022Observational
- Identifying requirements for RSK2 specific inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2021Article
- Wdr1 and cofilin are necessary mediators of immune-cell-specific apoptosis triggered by Tecfidera.Nature communications · 2021Article
- The medicinal chemistry of mitochondrial dysfunction: a critical overview of efforts to modulate mitochondrial health.RSC medicinal chemistry · 2021Review
- Matriptase activation of Gq drives epithelial disruption and inflammation via RSK and DUOX.eLife · 2021Article
- PERK Pathway and Neurodegenerative Disease: To Inhibit or to Activate?Biomolecules · 2021Review
- Key Signaling Pathways in Psoriasis: Recent Insights from Antipsoriatic Therapeutics.Psoriasis (Auckland, N.Z.) · 2021Review
- Electrophile Signaling and Emerging Immuno- and Neuro-modulatory Electrophilic Pharmaceuticals.Frontiers in aging neuroscience · 2020Article
- Dimethyl Fumarate Targets MSK1, RSK1, 2 and IKKα/β Kinases and Regulates NF-κB /p65 Activation in Psoriasis: A Demonstration of the Effect on Peripheral Blood Mononuclear Cells, Drawn from Two Patients with Severe Psoriasis Before and After Treatment with Dimethyl Fumarate.Psoriasis (Auckland, N.Z.) · 2020Article
- No evidence for interactions of dimethylfumarate (DMF) and its main metabolite monomethylfumarate (MMF) with human cytochrome P450 (CYP) enzymes and the P-glycoprotein (P-gp) drug transporter.Pharmacology research & perspectives · 2019Article
- Genie in a bottle: controlled release helps tame natural polypharmacology?Current opinion in chemical biology · 2019Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Dimethyl fumarate (DMF) has been applied for decades in the treatment of psoriasis and now also multiple sclerosis. However, the mechanism of action has remained obscure and involves high dose over long time of this small, reactive compound implicating many potential targets. Based on a 1.9 Å resolution crystal structure of the C-terminal kinase domain of the mouse p90 Ribosomal S6 Kinase 2 (RSK2) inhibited by DMF we describe a central binding site in RSKs and the closely related Mitogen and Stress-activated Kinases (MSKs). DMF reacts covalently as a Michael acceptor to a conserved cysteine residue in the αF-helix of RSK/MSKs. Binding of DMF prevents the activation loop of the kinase from engaging substrate, and stabilizes an auto-inhibitory αL-helix, thus pointing to an effective, allosteric mechanism of kinase inhibition. The biochemical and cell biological characteristics of DMF inhibition of RSK/MSKs are consistent with the clinical protocols of DMF treatment.
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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.