ArticleChemMedChem2014
Small molecules that target the toxic RNA in myotonic dystrophy type 2.
Article in ChemMedChem, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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
15 citing papers in PubMed.
- Small molecule targeting r(UGGAA)Nature communications · 2021Article
- Unnatural bases for recognition of noncoding nucleic acid interfaces.Biopolymers · 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
- Expanded DNA and RNA Trinucleotide Repeats in Myotonic Dystrophy Type 1 Select Their Own Multitarget, Sequence-Selective Inhibitors.Biochemistry · 2020Article
- Short Tandem Repeat-Enriched Architectural RNAs in Nuclear Bodies: Functions and Associated Diseases.Non-coding RNA · 2020Review
- Mitigating RNA Toxicity in Myotonic Dystrophy using Small Molecules.International journal of molecular sciences · 2019Review
- AQAMAN, a bisamidine-based inhibitor of toxic protein inclusions in neurons, ameliorates cytotoxicity in polyglutamine disease models.The Journal of biological chemistry · 2019Article
- Finely tuned conformational dynamics regulate the protective function of the lncRNA MALAT1 triple helix.Nucleic acids research · 2019Article
- 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
- Biomolecular diagnosis of myotonic dystrophy type 2: a challenging approach.Journal of neurology · 2017Review
- Reduction of Huntington's Disease RNA Foci by CAG Repeat-Targeting Reagents.Frontiers in cellular neuroscience · 2017Article
- A Potent Inhibitor of Protein Sequestration by Expanded Triplet (CUG) Repeats that Shows Phenotypic Improvements in a Drosophila Model of Myotonic Dystrophy.ChemMedChem · 2016Article
- Review
- Repeat-associated RNA structure and aberrant splicing.Biochimica et biophysica acta. Gene regulatory mechanismsReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
Abstract
Myotonic dystrophy type 2 (DM2) is caused by an expansion of CCTG repeats in the zinc-finger protein gene (ZNF9). Transcribed CCUG repeats sequester muscleblind-like protein 1 (MBNL1), an important alternative splicing regulator, preventing its normal function, leading to the disease phenotype. We describe a series of ligands that disrupt the MBNL1-r(CCUG)n interaction as potential lead agents for developing DM2 therapeutics. A previously reported triaminopyrimidine-acridine conjugate was a moderate inhibitor in vitro, however it proved to be poorly water-soluble and not cell-permeable. To improve its therapeutic potential, the new set of ligands maintained the key triaminopyrimidine recognition unit but replaced the acridine intercalator with a bisamidinium groove binder. The optimized ligands exhibit low micromolar inhibition potency to MBNL1-r(CCUG)8. Importantly, the ligands are the first to show the ability to disrupt the MBNL1-r(CCUG)n foci in DM2 model cell culture and exhibit low cytotoxicity.
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.