ArticleJournal of medicinal chemistry2012
Increased selectivity toward cytoplasmic versus mitochondrial ribosome confers improved efficiency of synthetic aminoglycosides in fixing damaged genes: a strategy for treatment of genetic diseases caused by nonsense mutations.
Article in Journal of medicinal chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
What it found
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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
46 citing papers in PubMed, 74 citations in OpenAlex.
- Phase 1 Renal Impairment Trial Results Supports Targeted Individualized Dosing of ELX-02 in Patients With Nephropathic Cystinosis.Journal of clinical pharmacology · 2021Trial
- RFFL-mediated protein quality control limits functional rescue of TRID-CFTR modulator combination therapy for cystic fibrosis nonsense mutations.Cellular and molecular life sciences : CMLS · 2026Article
- Recovery of α-L-fucosidase in fucosidosis nonsense variants by readthrough stimulation and release factor degradation.Disease models & mechanisms · 2026Article
- Review
- High-fidelity and differential nonsense suppression in live cells and a frontotemporal dementia allele with human transfer RNAs.Nucleic acids research · 2025Article
- Combinatorial biosynthesis of novel gentamicin derivatives with nonsense mutation readthrough activity and low cytotoxicity.Frontiers in pharmacology · 2025Article
- Novel readthrough agent suppresses nonsense mutations and restores functional type VII collagen and laminin 332 in epidermolysis bullosa.Molecular therapy. Nucleic acids · 2024Article
- Cystic Fibrosis Modulator Therapies: Bridging Insights from CF to other Membrane Protein Misfolding Diseases.Israel journal of chemistry · 2024Article
- Genetics of cystogenesis in base-edited human organoids reveal therapeutic strategies for polycystic kidney disease.Cell stem cell · 2024Article
- Readthrough Activators and Nonsense-Mediated mRNA Decay Inhibitor Molecules: Real Potential in Many Genetic Diseases Harboring Premature Termination Codons.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Therapeutic targeting ofUpsala journal of medical sciences · 2024Review
- Balancing Nonsense Mutation Readthrough and Toxicity of Designer Aminoglycosides for Treatment of Genetic Diseases.ACS medicinal chemistry letters · 2023Article
- The synthetic aminoglycoside ELX-02 induces readthrough of G550X-CFTR producing superfunctional protein that can be further enhanced by CFTR modulators.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- A Simple and Affordable Method to Create Nonsense Mutation Clones of p53 for Studying the Premature Termination Codon Readthrough Activity of PTC124.Biomedicines · 2023Article
- PTC124 Rescues Nonsense Mutation of Two Tumor Suppressor GenesBiomedicines · 2022Article
- Ataluren suppresses a premature termination codon in an MPS I-H mouse.Journal of molecular medicine (Berlin, Germany) · 2022Article
- One Size Does Not Fit All: The Past, Present and Future of Cystic Fibrosis Causal Therapies.Cells · 2022Review
- Identifying targets to prevent aminoglycoside ototoxicity.Molecular and cellular neurosciences · 2022Review
- Reducing the Toxicity of Designer Aminoglycosides as Nonsense Mutation Readthrough Agents for Therapeutic Targets.ACS medicinal chemistry letters · 2021Article
- Stop Codon Context-Specific Induction of Translational Readthrough.Biomolecules · 2021Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Compelling evidence is now available that gentamicin and Geneticin (G418) can induce the mammalian ribosome to suppress disease-causing nonsense mutations and partially restore the expression of functional proteins. However, toxicity and relative lack of efficacy at subtoxic doses limit the use of gentamicin for suppression therapy. Although G418 exhibits the strongest activity, it is very cytotoxic even at low doses. We describe here the first systematic development of the novel aminoglycoside (S)-11 exhibiting similar in vitro and ex vivo activity to that of G418, while its cell toxicity is significantly lower than those of gentamicin and G418. Using a series of biochemical assays, we provide proof of principle that antibacterial activity and toxicity of aminoglycosides can be dissected from their suppression activity. The data further indicate that the increased specificity toward cytoplasmic ribosome correlates with the increased activity and that the decreased specificity toward mitochondrial ribosome confers the lowered cytotoxicity.
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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.