ArticlePloS one2018
The minor gentamicin complex component, X2, is a potent premature stop codon readthrough molecule with therapeutic potential.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 38 citations in OpenAlex.
- Combinatorial biosynthesis of novel gentamicin derivatives with nonsense mutation readthrough activity and low cytotoxicity.Frontiers in pharmacology · 2025Article
- From Polymeric Nanoformulations to Polyphenols-Strategies for Enhancing the Efficacy and Drug Delivery of Gentamicin.Antibiotics (Basel, Switzerland) · 2024Review
- Therapeutic targeting ofUpsala journal of medical sciences · 2024Review
- Synthesis of Gentamicins C1, C2, and C2a and Antiribosomal and Antibacterial Activity of Gentamicins B1, C1, C1a, C2, C2a, C2b, and X2.ACS infectious diseases · 2023Article
- Pharmaceuticals Promoting Premature Termination Codon Readthrough: Progress in Development.Biomolecules · 2023Review
- Recoding of Nonsense Mutation as a Pharmacological Strategy.Biomedicines · 2023Review
- Innovations in the Treatment of Dystrophic Epidermolysis Bullosa (DEB): Current Landscape and Prospects.Therapeutics and clinical risk management · 2023Review
- Translational readthrough of nonsense mutant TP53 by mRNA incorporation of 5-Fluorouridine.Cell death & disease · 2022Article
- Small Molecules for Enhancing the Precision and Safety of Genome Editing.Molecules (Basel, Switzerland) · 2022Review
- CRISPR-SCReT (CRISPR-Stop Codon Read Through) method to control Cas9 expression for gene editing.Gene therapy · 2022Article
- NanoLuc reporters identifyiScience · 2022Article
- Application of topical gentamicin-a new era in the treatment of genodermatosis.World journal of pediatrics : WJP · 2021Review
- 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
- Nanomedicine for Gene Delivery and Drug Repurposing in the Treatment of Muscular Dystrophies.Pharmaceutics · 2021Review
- Selective toxicity of antibacterial agents-still a valid concept or do we miss chances and ignore risks?Infection · 2021Review
- Dissociating antibacterial from ototoxic effects of gentamicin C-subtypes.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Leading edge: emerging drug, cell, and gene therapies for junctional epidermolysis bullosa.Expert opinion on biological therapy · 2020Review
- Synthesis of Gentamicin Minor Components: Gentamicin B1 and Gentamicin X2.Organic letters · 2020Article
- 2,6-Diaminopurine as a highly potent corrector of UGA nonsense mutations.Nature communications · 2020Article
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Authors and funding
21 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nonsense mutations, resulting in a premature stop codon in the open reading frame of mRNAs are responsible for thousands of inherited diseases. Readthrough of premature stop codons by small molecule drugs has emerged as a promising therapeutic approach to treat disorders resulting from premature termination of translation. The aminoglycoside antibiotics are a class of molecule known to promote readthrough at premature termination codons. Gentamicin consists of a mixture of major and minor aminoglycoside components. Here, we investigated the readthrough activities of the individual components and show that each of the four major gentamicin complex components representing 92-99% of the complex each had similar potency and activity to that of the complex itself. In contrast, a minor component (gentamicin X2) was found to be the most potent and active readthrough component in the gentamicin complex. The known oto- and nephrotoxicity associated with aminoglycosides preclude long-term use as readthrough agents. Thus, we evaluated the components of the gentamicin complex as well as the so-called "designer" aminoglycoside, NB124, for in vitro and in vivo safety. In cells, we observed that gentamicin X2 had a safety/readthrough ratio (cytotoxicity/readthrough potency) superior to that of gentamicin, G418 or NB124. In rodents, we observed that gentamicin X2 showed a safety profile that was superior to G418 overall including reduced nephrotoxicity. These results support further investigation of gentamicin X2 as a therapeutic readthrough agent.
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