ArticleNucleic acids research2012
From dynamic combinatorial 'hit' to lead: in vitro and in vivo activity of compounds targeting the pathogenic RNAs that cause myotonic dystrophy.
Article in Nucleic acids research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
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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
39 citing papers in PubMed, 78 citations in OpenAlex.
- Targeting Expanded CUG and CTG Repeats as a Therapeutic Approach for Myotonic Dystrophy Type 1 (DM1).ChemMedChem · 2026Review
- Molecular genetics of myotonic dystrophy and the evolution of therapeutic approaches.Journal of human genetics · 2025Review
- The Druggable Transcriptome Project: From Chemical Probes to Precision Medicines.Biochemistry · 2025Review
- NMR structures of small molecules bound to a model of a CUG RNA repeat expansion.Bioorganic & medicinal chemistry letters · 2024Review
- NMR structures of small molecules bound to a model of an RNA CUG repeat expansion.bioRxiv : the preprint server for biology · 2024Article
- Quantitative Structure-Activity Relationship (QSAR) Study Predicts Small-Molecule Binding to RNA Structure.Journal of medicinal chemistry · 2022Article
- Brain Pathogenesis and Potential Therapeutic Strategies in Myotonic Dystrophy Type 1.Frontiers in aging neuroscience · 2021Review
- Target-Directed Approaches for Screening Small Molecules against RNA Targets.SLAS discovery : advancing life sciences R & D · 2020Review
- Template-guided selection of RNA ligands using imine-based dynamic combinatorial chemistry.Chemical communications (Cambridge, England) · 2020Article
- Mitigating RNA Toxicity in Myotonic Dystrophy using Small Molecules.International journal of molecular sciences · 2019Review
- Insights into the development of chemical probes for RNA.Nucleic acids research · 2018Article
- Targeting RNA in mammalian systems with small molecules.Wiley interdisciplinary reviews. RNA · 2018Review
- Using Genome Sequence to Enable the Design of Medicines and Chemical Probes.Chemical reviews · 2018Review
- HIV-1 Frameshift RNA-Targeted Triazoles Inhibit Propagation of Replication-Competent and Multi-Drug-Resistant HIV in Human Cells.ACS chemical biology · 2017Article
- New developments in RAN translation: insights from multiple diseases.Current opinion in genetics & development · 2017Review
- Antiparallel Dynamic Covalent Chemistries.Journal of the American Chemical Society · 2017Article
- The Emerging Role of RNA as a Therapeutic Target for Small Molecules.Cell chemical biology · 2016Review
- Probing the geometric constraints of RNA binding via dynamic covalent chemistry.Bioorganic & medicinal chemistry · 2016Article
- Identification of Plant-derived Alkaloids with Therapeutic Potential for Myotonic Dystrophy Type I.The Journal of biological chemistry · 2016Article
- N-Methylation as a Strategy for Enhancing the Affinity and Selectivity of RNA-binding Peptides: Application to the HIV-1 Frameshift-Stimulating RNA.ACS chemical biology · 2016Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The myotonic dystrophies (DM) are human diseases in which the accumulation of toxic RNA (CUG or CCUG) repeats in the cell causes sequestration of splicing factors, including MBNL1, leading to clinical symptoms such as muscle wasting and myotonia. We previously used Dynamic Combinatorial Chemistry to identify the first compounds known to inhibit (CUG)-MBNL1 binding in vitro. We now report transformation of those compounds into structures with activity in vivo. Introduction of a benzo[g]quinoline substructure previously unknown in the context of RNA recognition, as well as other modifications, provided several molecules with enhanced binding properties, including compounds with strong selectivity for CUG repeats over CAG repeats or CAG-CUG duplex RNA. Compounds readily penetrate cells, and improve luciferase activity in a mouse myoblast assay in which enzyme function is coupled to a release of nuclear CUG-RNA retention. Most importantly, two compounds are able to partially restore splicing in a mouse model of DM1.
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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.