ArticleJournal of the American Chemical Society2012
Design of a bioactive small molecule that targets the myotonic dystrophy type 1 RNA via an RNA motif-ligand database and chemical similarity searching.
Article in Journal of the American Chemical Society, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 1 of them a synthesis that pooled it.
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
87 citing papers in PubMed, 1 synthesis or guideline pooled it, 144 citations in OpenAlex.
- RNA Drugs and RNA Targets for Small Molecules: Principles, Progress, and Challenges.Pharmacological reviews · 2020Pooled it
- Integrative analysis of drug-gene signatures in human pluripotent stem cells reveals prazosin as a novel SQSTM1 regulator for ALS therapeutics.Stem cell reports · 2026Article
- Targeting Expanded CUG and CTG Repeats as a Therapeutic Approach for Myotonic Dystrophy Type 1 (DM1).ChemMedChem · 2026Review
- Article
- A Live-Cell NanoBRET Assay to Monitor RNA-Protein Interactions and Their Inhibition by Small Molecules.ACS central science · 2025Article
- Evaluation of single-template ligand-based methods for the discovery of small-molecule nucleic acid binders.Briefings in bioinformatics · 2025Article
- Lacosamide Interaction with Expanded CGG Repeats RNA and Its Role in Modulating Poly-Glycine Protein-Mediated Toxicity in Fragile‑X Tremor/Ataxia Syndrome.ACS pharmacology & translational science · 2025Article
- Molecular genetics of myotonic dystrophy and the evolution of therapeutic approaches.Journal of human genetics · 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
- Splicing mutations in the CFTR gene as therapeutic targets.Gene therapy · 2022Review
- 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
- A Small Molecule that Binds an RNA Repeat Expansion Stimulates Its Decay via the Exosome Complex.Cell chemical biology · 2021Article
- Small molecule-RNA targeting: starting with the fundamentals.Chemical communications (Cambridge, England) · 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
- Target-Directed Approaches for Screening Small Molecules against RNA Targets.SLAS discovery : advancing life sciences R & D · 2020Review
- Optimization of the Linker Domain in a Dimeric Compound that Degrades an r(CUG) Repeat Expansion in Cells.Journal of medicinal chemistry · 2020Article
- Innovative Therapeutic and Delivery Approaches Using Nanotechnology to Correct Splicing Defects Underlying Disease.Frontiers in genetics · 2020Review
- Curcumin Regulates the r(CGG)Frontiers in neuroscience · 2020Article
27 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
11 authors at 4 institutions in 1 country.
Funding
Abstract
Myotonic dystrophy type 1 (DM1) is a triplet repeating disorder caused by expanded CTG repeats in the 3'-untranslated region of the dystrophia myotonica protein kinase (DMPK) gene. The transcribed repeats fold into an RNA hairpin with multiple copies of a 5'CUG/3'GUC motif that binds the RNA splicing regulator muscleblind-like 1 protein (MBNL1). Sequestration of MBNL1 by expanded r(CUG) repeats causes splicing defects in a subset of pre-mRNAs including the insulin receptor, the muscle-specific chloride ion channel, sarco(endo)plasmic reticulum Ca(2+) ATPase 1, and cardiac troponin T. Based on these observations, the development of small-molecule ligands that target specifically expanded DM1 repeats could be of use as therapeutics. In the present study, chemical similarity searching was employed to improve the efficacy of pentamidine and Hoechst 33258 ligands that have been shown previously to target the DM1 triplet repeat. A series of in vitro inhibitors of the RNA-protein complex were identified with low micromolar IC(50)'s, which are >20-fold more potent than the query compounds. Importantly, a bis-benzimidazole identified from the Hoechst query improves DM1-associated pre-mRNA splicing defects in cell and mouse models of DM1 (when dosed with 1 mM and 100 mg/kg, respectively). Since Hoechst 33258 was identified as a DM1 binder through analysis of an RNA motif-ligand database, these studies suggest that lead ligands targeting RNA with improved biological activity can be identified by using a synergistic approach that combines analysis of known RNA-ligand interactions with chemical similarity searching.
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.