ArticleCommunications biology2020
Ebselen as template for stabilization of A4V mutant dimer for motor neuron disease therapy.
Article in Communications biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 43 citations in OpenAlex.
- Hitting Coronaviruses Where It Hurts: Antiviral Strategies Targeting Viral Proteins.ChemMedChem · 2026Review
- Stabilized real-time Brillouin microscopy reveals fractal organization of protein condensates in living cells.Nature communications · 2026Article
- Inhibitory effect of Fisetin against the aggregation process of SOD1 E100K mutant: computer-based drug design as a potential therapeutic for ALS disease.Frontiers in chemistry · 2025Article
- Discovery of Novel Inhibitors against ALS-Related SOD1(A4V) Aggregation through the Screening of a Chemical Library Using Differential Scanning Fluorimetry (DSF).Pharmaceuticals (Basel, Switzerland) · 2024Article
- Ebselen analogues delay disease onset and its course in fALS by on-target SOD-1 engagement.Scientific reports · 2024Article
- Protein aggregation and therapeutic strategies in SOD1- and TDP-43- linked ALS.Frontiers in molecular biosciences · 2024Review
- Structural insights into the modulation Of SOD1 aggregation By a fungal metabolite Phialomustin-B: Therapeutic potential in ALS.PloS one · 2024Article
- Evaluating protein cross-linking as a therapeutic strategy to stabilize SOD1 variants in a mouse model of familial ALS.PLoS biology · 2024Article
- Small molecules targeting different cellular pathologies for the treatment of amyotrophic lateral sclerosis.Medicinal research reviews · 2023Review
- Intrathecal Pseudodelivery of Drugs in the Therapy of Neurodegenerative Diseases: Rationale, Basis and Potential Applications.Pharmaceutics · 2023Review
- Simulating chalcogen bonding using molecular mechanics: a pseudoatom approach to model ebselen.Journal of molecular modeling · 2022Article
- First Principles Calculation of Protein-Protein Dimer Affinities of ALS-Associated SOD1 Mutants.Frontiers in molecular biosciences · 2022Article
- Ebselen and Analogues: Pharmacological Properties and Synthetic Strategies for Their Preparation.Molecules (Basel, Switzerland) · 2021Review
- Identification of ebselen and its analogues as potent covalent inhibitors of papain-like protease from SARS-CoV-2.Scientific reports · 2021Article
- Crystal structure of SARS-CoV-2 papain-like protease.Acta pharmaceutica Sinica. B · 2021Article
- Crystallization and structure of ebselen bound to Cys141 of human inositol monophosphatase.Acta crystallographica. Section F, Structural biology communications · 2020Article
- Novel Selenium-based compounds with therapeutic potential for SOD1-linked amyotrophic lateral sclerosis.EBioMedicine · 2020Article
- Molecular and pharmacological chaperones for SOD1.Biochemical Society transactions · 2020Review
- Amyotrophic Lateral Sclerosis: Proteins, Proteostasis, Prions, and Promises.Frontiers in cellular neuroscience · 2020Article
- A Novel SOD1 Intermediate Oligomer, Role of Free Thiols and Disulfide Exchange.Frontiers in neuroscience · 2020Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 3 countries.
Funding
Abstract
Mutations to the gene encoding superoxide dismutase-1 (SOD1) were the first genetic elements discovered that cause motor neuron disease (MND). These mutations result in compromised SOD1 dimer stability, with one of the severest and most common mutations Ala4Val (A4V) displaying a propensity to monomerise and aggregate leading to neuronal death. We show that the clinically used ebselen and related analogues promote thermal stability of A4V SOD1 when binding to Cys111 only. We have developed a A4V SOD1 differential scanning fluorescence-based assay on a C6S mutation background that is effective in assessing suitability of compounds. Crystallographic data show that the selenium atom of these compounds binds covalently to A4V SOD1 at Cys111 at the dimer interface, resulting in stabilisation. This together with chemical amenability for hit expansion of ebselen and its on-target SOD1 pharmacological chaperone activity holds remarkable promise for structure-based therapeutics for MND using ebselen as a template.
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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.