ArticleACS chemical biology2012
Rationally designed small molecules targeting the RNA that causes myotonic dystrophy type 1 are potently bioactive.
Article in ACS chemical biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 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
91 citing papers in PubMed, 127 citations in OpenAlex.
- DLRNA-BERTa: a transformer approach for predicting molecule-RNA binding affinities.Briefings in bioinformatics · 2026Article
- 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
- Modified Polycyclic Compounds Rescue Mis-splicing in Myotonic Dystrophy Type 1 Disease Models.ACS chemical 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
- Docking and Molecular Dynamics Simulation-Based Analysis of Advanced Small-Molecule Kinase Inhibitors Identified pre-let-7 miRNA Binders.Chembiochem : a European journal of chemical biology · 2025Article
- Discovery of RNA-Reactive Small Molecules Guides the Design of Electrophilic Modules for RNA-Specific Covalent Binders.Journal of the American Chemical Society · 2025Article
- Promoter-targeted small RNA duplexes increase MBNL1 transcription and mitigate myotonic dystrophy-associated spliceopathy.Nucleic acids research · 2025Article
- The Druggable Transcriptome Project: From Chemical Probes to Precision Medicines.Biochemistry · 2025Review
- Cognate RNA-Binding Modes by the Alternative-Splicing Regulator MBNL1 Inferred from Molecular Dynamics.International journal of molecular sciences · 2022Article
- Discovery of small molecules that target a tertiary-structured RNA.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Targeting RNA structures with small molecules.Nature reviews. Drug discovery · 2022Review
- NMR determination of the 2:1 binding complex of naphthyridine carbamate dimer (NCD) and CGG/CGG triad in double-stranded DNA.Nucleic acids research · 2022Article
- Novel bivalent ligands carrying potential antinociceptive effects by targeting putative mu opioid receptor and chemokine receptor CXCR4 heterodimers.Bioorganic chemistry · 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
- Nanomedicine for Gene Delivery and Drug Repurposing in the Treatment of Muscular Dystrophies.Pharmaceutics · 2021Review
- Article
- A general fragment-based approach to identify and optimize bioactive ligands targeting RNA.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Macrocyclization of a Ligand Targeting a Toxic RNA Dramatically Improves Potency.Chembiochem : a European journal of chemical biology · 2020Article
- 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
31 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
RNA is an important drug target, but it is difficult to design or discover small molecules that modulate RNA function. In the present study, we report that rationally designed, modularly assembled small molecules that bind the RNA that causes myotonic dystrophy type 1 (DM1) are potently bioactive in cell culture models. DM1 is caused when an expansion of r(CUG) repeats, or r(CUG)(exp), is present in the 3' untranslated region (UTR) of the dystrophia myotonica protein kinase (DMPK) mRNA. r(CUG)(exp) folds into a hairpin with regularly repeating 5'CUG/3'GUC motifs and sequesters muscleblind-like 1 protein (MBNL1). A variety of defects are associated with DM1, including (i) formation of nuclear foci, (ii) decreased translation of DMPK mRNA due to its nuclear retention, and (iii) pre-mRNA splicing defects due to inactivation of MBNL1, which controls the alternative splicing of various pre-mRNAs. Previously, modularly assembled ligands targeting r(CUG)(exp) were designed using information in an RNA motif-ligand database. These studies showed that a bis-benzimidazole (H) binds the 5'CUG/3'GUC motif in r(CUG)(exp.) Therefore, we designed multivalent ligands to bind simultaneously multiple copies of this motif in r(CUG)(exp). Herein, we report that the designed compounds improve DM1-associated defects including improvement of translational and pre-mRNA splicing defects and the disruption of nuclear foci. These studies may establish a foundation to exploit other RNA targets in genomic sequence.
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.