ArticleACS chemical biology2012
A small molecule that targets r(CGG)(exp) and improves defects in fragile X-associated tremor ataxia syndrome.
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 71 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
71 citing papers in PubMed, 1 synthesis or guideline pooled it.
- RNA Drugs and RNA Targets for Small Molecules: Principles, Progress, and Challenges.Pharmacological reviews · 2020Pooled it
- Targeting RNA binding proteins with small-molecule inhibitors: Advances, challenges, and therapeutic opportunities.Acta pharmaceutica Sinica. B · 2026Review
- Structure-Guided Design of a Bioactive Covalent Small Molecule Targeting a Riboswitch.Journal of the American Chemical Society · 2025Article
- FXTAS presenting with cervical dystonia as the initial symptom: Considering FXTAS in the clinical evaluation of cervical dystonia.eNeurologicalSci · 2025Article
- Advances in the Structure of GGGGCC Repeat RNA Sequence and Its Interaction with Small Molecules and Protein Partners.Molecules (Basel, Switzerland) · 2023Review
- Native functions of short tandem repeats.eLife · 2023Article
- Mouse models of fragile X-related disorders.Disease models & mechanisms · 2023Review
- G-Quadruplexes in Repeat Expansion Disorders.International journal of molecular sciences · 2023Review
- Review
- Expansion of the RNAStructuromeDB to include secondary structural data spanning the human protein-coding transcriptome.Scientific reports · 2022Article
- Mechanisms of theInternational journal of molecular sciences · 2022Review
- Fluorescence-Based Binding Characterization of Small Molecule Ligands Targeting CUG RNA Repeats.International journal of molecular sciences · 2022Article
- Neurodegenerative diseases associated with non-coding CGG tandem repeat expansions.Nature reviews. Neurology · 2022Review
- Small Molecule Screening Discovers Compounds that Reduce FMRpolyG Protein Aggregates and Splicing Defect Toxicity in Fragile X-Associated Tremor/Ataxia Syndrome.Molecular neurobiology · 2022Article
- Noncoding RNA therapeutics for substance use disorder.Advances in drug and alcohol research · 2022Article
- Non-canonical DNA/RNA structures associated with the pathogenesis of Fragile X-associated tremor/ataxia syndrome and Fragile X syndrome.Frontiers in genetics · 2022Review
- Trinucleotide CGG Repeat Diseases: An Expanding Field of Polyglycine Proteins?Frontiers in genetics · 2022Review
- (Dys)function Follows Form: Nucleic Acid Structure, Repeat Expansion, and Disease Pathology inInternational journal of molecular sciences · 2021Review
- Short antisense oligonucleotides alleviate the pleiotropic toxicity of RNA harboring expanded CGG repeats.Nature communications · 2021Article
- Therapeutic Development for CGG Repeat Expansion-Associated Neurodegeneration.Frontiers in cellular neuroscience · 2021Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
The development of small molecule chemical probes or therapeutics that target RNA remains a significant challenge despite the great interest in such compounds. The most significant barrier to compound development is defining which chemical and RNA motif spaces interact specifically. Herein, we describe a bioactive small molecule probe that targets expanded r(CGG) repeats, or r(CGG)(exp), that causes Fragile X-associated Tremor Ataxia Syndrome (FXTAS). The compound was identified by using information on the chemotypes and RNA motifs that interact. Specifically, 9-hydroxy-5,11-dimethyl-2-(2-(piperidin-1-yl)ethyl)-6H-pyrido[4,3-b]carbazol-2-ium binds the 5'CGG/3'GGC motifs in r(CGG)(exp) and disrupts a toxic r(CGG)(exp)-protein complex in vitro. Structure-activity relationship studies determined that the alkylated pyridyl and phenolic side chains are important chemotypes that drive molecular recognition of r(CGG)(exp). Importantly, the compound is efficacious in FXTAS model cellular systems as evidenced by its ability to improve FXTAS-associated pre-mRNA splicing defects and to reduce the size and number of r(CGG)(exp)-containing nuclear foci. This approach may establish a general strategy to identify lead ligands that target RNA while also providing a chemical probe to dissect the varied mechanisms by which r(CGG)(exp) promotes toxicity.
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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.