ArticleNucleic acids research2014
Lomofungin and dilomofungin: inhibitors of MBNL1-CUG RNA binding with distinct cellular effects.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
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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.
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Who cites it
42 citing papers in PubMed, 59 citations in OpenAlex.
- Therapeutic Strategies Targeting the Molecular Pathogenesis of Myotonic Dystrophy Type 1: Current Status and Future Directions.Molecular diagnosis & therapy · 2026Review
- A chemoinformatics-guided platform for efficient discovery of RNA-binding small molecules: Proof-of-concept for myotonic dystrophy type 1.bioRxiv : the preprint server for biology · 2026Article
- Targeting Expanded CUG and CTG Repeats as a Therapeutic Approach for Myotonic Dystrophy Type 1 (DM1).ChemMedChem · 2026Review
- Predicting small molecule-RNA interactions without RNA tertiary structures.Nature biotechnology · 2026Article
- Discovery of RNA-Reactive Small Molecules Guides the Design of Electrophilic Modules for RNA-Specific Covalent Binders.Journal of the American Chemical Society · 2025Article
- Functions of the Muscleblind-like protein family and their role in disease.Cell communication and signaling : CCS · 2025Review
- Small Molecule Screening Identifies HSP90 as a Modifier of RNA Foci in Myotonic Dystrophy Type 1.Molecular and cellular biology · 2025Article
- Using the structural diversity of RNA: protein interfaces to selectively target RNA with small molecules in cells: methods and perspectives.Frontiers in molecular biosciences · 2023Review
- Study of an RNA-Focused DNA-Encoded Library Informs Design of a Degrader of a r(CUG) Repeat Expansion.Journal of the American Chemical Society · 2022Article
- Fluorescence-Based Binding Characterization of Small Molecule Ligands Targeting CUG RNA Repeats.International journal of molecular sciences · 2022Article
- Small Molecule Screening Discovers Compounds that Reduce FMRpolyG Protein Aggregates and Splicing Defect Toxicity in Fragile X-Associated Tremor/Ataxia Syndrome.Molecular neurobiology · 2022Article
- Pharmacotherapy alleviates pathological changes in human direct reprogrammed neuronal cell model of myotonic dystrophy type 1.PloS one · 2022Article
- In Vitro Ubiquitination Platform Identifies Methyl Ellipticiniums as Ubiquitin Ligase Inhibitors.SLAS discovery : advancing life sciences R & D · 2021Article
- Brain Pathogenesis and Potential Therapeutic Strategies in Myotonic Dystrophy Type 1.Frontiers in aging neuroscience · 2021Review
- The Dimeric Form of 1,3-Diaminoisoquinoline Derivative Rescued the Mis-splicing of Atp2a1 and Clcn1 Genes in Myotonic Dystrophy Type 1 Mouse Model.Chemistry (Weinheim an der Bergstrasse, Germany) · 2020Article
- Exploring the Potential of Small Molecule-Based Therapeutic Approaches for Targeting Trinucleotide Repeat Disorders.Molecular neurobiology · 2020Review
- A CTG repeat-selective chemical screen identifies microtubule inhibitors as selective modulators of toxic CUG RNA levels.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Mitigating RNA Toxicity in Myotonic Dystrophy using Small Molecules.International journal of molecular sciences · 2019Review
- Targeting RNA with Small Molecules To Capture Opportunities at the Intersection of Chemistry, Biology, and Medicine.Journal of the American Chemical Society · 2019Article
- Myotonic Dystrophies: Targeting Therapies for Multisystem Disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2018Review
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
Myotonic dystrophy type 1 (DM1) is a dominantly inherited neuromuscular disorder resulting from expression of RNA containing an expanded CUG repeat (CUG(exp)). The pathogenic RNA is retained in nuclear foci. Poly-(CUG) binding proteins in the Muscleblind-like (MBNL) family are sequestered in foci, causing misregulated alternative splicing of specific pre-mRNAs. Inhibitors of MBNL1-CUG(exp) binding have been shown to restore splicing regulation and correct phenotypes in DM1 models. We therefore conducted a high-throughput screen to identify novel inhibitors of MBNL1-(CUG)12 binding. The most active compound was lomofungin, a natural antimicrobial agent. We found that lomofungin undergoes spontaneous dimerization in DMSO, producing dilomofungin, whose inhibition of MBNL1-(CUG)12 binding was 17-fold more potent than lomofungin itself. However, while dilomofungin displayed the desired binding characteristics in vitro, when applied to cells it produced a large increase of CUG(exp) RNA in nuclear foci, owing to reduced turnover of the CUG(exp) transcript. By comparison, the monomer did not induce CUG(exp) accumulation in cells and was more effective at rescuing a CUG(exp)-induced splicing defect. These results support the feasibility of high-throughput screens to identify compounds targeting toxic RNA, but also demonstrate that ligands for repetitive sequences may have unexpected effects on RNA decay.
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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 Socratic graph.