ArticleJournal of the American Chemical Society2014
Targeting toxic RNAs that cause myotonic dystrophy type 1 (DM1) with a bisamidinium inhibitor.
Article in Journal of the American Chemical Society, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 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
58 citing papers in PubMed, 101 citations in OpenAlex.
- RNA-binding landscape of amiloride: large-scale profiling and structural basis of U-U mismatch recognition.RSC chemical biology · 2026Article
- Targeting Expanded CUG and CTG Repeats as a Therapeutic Approach for Myotonic Dystrophy Type 1 (DM1).ChemMedChem · 2026Review
- Streamlined Fragment-Based Discovery Platform for Targeting Structured RNAs.ACS chemical biology · 2025Article
- Article
- Large-scale analysis of small molecule-RNA interactions using multiplexed RNA structure libraries.Communications chemistry · 2024Article
- Small molecules modulating RNA splicing: a review of targets and future perspectives.RSC medicinal chemistry · 2024Review
- Small molecule approaches to targeting RNA.Nature reviews. Chemistry · 2024Review
- An Encodable Scaffold for Sequence-Specific Recognition of Duplex RNA.Angewandte Chemie (International ed. in English) · 2023Article
- Article
- Development of Fluorescent Turn-On Probes for CAG-RNA Repeats.Biosensors · 2022Article
- Selective and Reversible Ligand Assembly on the DNA and RNA Repeat Sequences in Myotonic Dystrophy.Chembiochem : a European journal of chemical biology · 2022Article
- Surface-enhanced Raman spectroscopy for drug discovery: peptide-RNA binding.Analytical and bioanalytical chemistry · 2022Article
- Fluorescence-Based Binding Characterization of Small Molecule Ligands Targeting CUG RNA Repeats.International journal of molecular sciences · 2022Article
- A small-molecule fluorescence probe ANP77 for sensing RNA internal loop of C, U and A/CC motifs and their binding molecules.Nucleic acids research · 2021Article
- A Novel Minor Groove Binder as a Potential Therapeutic Agent for Myotonic Dystrophy Type 1.ChemMedChem · 2021Article
- CAG RNAs induce DNA damage and apoptosis by silencingProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Unnatural bases for recognition of noncoding nucleic acid interfaces.Biopolymers · 2021Review
- Design of novel small molecule base-pair recognizers of toxic CUG RNA transcripts characteristics of DM1.Computational and structural biotechnology journal · 2021Article
- Targeting RNA structures in diseases with small molecules.Essays in biochemistry · 2020Review
- 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
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 3 institutions in 3 countries.
Funding
Abstract
A working hypothesis for the pathogenesis of myotonic dystrophy type 1 (DM1) involves the aberrant sequestration of an alternative splicing regulator, MBNL1, by expanded CUG repeats, r(CUG)(exp). It has been suggested that a reversal of the myotonia and potentially other symptoms of the DM1 disease can be achieved by inhibiting the toxic MBNL1-r(CUG)(exp) interaction. Using rational design, we discovered an RNA-groove binding inhibitor (ligand 3) that contains two triaminotriazine units connected by a bisamidinium linker. Ligand 3 binds r(CUG)12 with a low micromolar affinity (K(d) = 8 ± 2 μM) and disrupts the MBNL1-r(CUG)12 interaction in vitro (K(i) = 8 ± 2 μM). In addition, ligand 3 is cell and nucleus permeable, exhibits negligible toxicity to mammalian cells, dissolves MBNL1-r(CUG)(exp) ribonuclear foci, and restores misregulated splicing of IR and cTNT in a DM1 cell culture model. Importantly, suppression of r(CUG)(exp) RNA-induced toxicity in a DM1 Drosophila model was observed after treatment with ligand 3. These results suggest ligand 3 as a lead for the treatment of DM1.
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.