ArticlePloS one2019
The antimalarial drug mefloquine enhances TP53 premature termination codon readthrough by aminoglycoside G418.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- Translational readthrough therapy for ADPKD induces polycystin1 expression and partially rescues functional deficits in PKD1 mutant cells.Scientific reports · 2025Article
- Animal models of lung cancer: Phenotypic comparison of different animal models of lung cancer and their application in the study of mechanisms.Animal models and experimental medicine · 2025Review
- Therapeutic Potential of Translational Readthrough at Disease-Associated Premature Termination Codons From Tumor Suppressor Genes.IUBMB life · 2025Review
- Mechanism of read-through enhancement by aminoglycosides and mefloquine.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Anticodon-edited tRNA enables translational readthrough of COL4A5 premature termination codons.PloS one · 2025Article
- Combinatorial biosynthesis of novel gentamicin derivatives with nonsense mutation readthrough activity and low cytotoxicity.Frontiers in pharmacology · 2025Article
- Genetics of cystogenesis in base-edited human organoids reveal therapeutic strategies for polycystic kidney disease.Cell stem cell · 2024Article
- Nonsense mutation suppression is enhanced by targeting different stages of the protein synthesis process.PLoS biology · 2023Article
- Evaluation of Novel Enhancer Compounds in Gentamicin-Mediated Readthrough of Nonsense Mutations in Rett Syndrome.International journal of molecular sciences · 2023Article
- Pharmaceuticals Promoting Premature Termination Codon Readthrough: Progress in Development.Biomolecules · 2023Review
- Review
- PTC124 Rescues Nonsense Mutation of Two Tumor Suppressor GenesBiomedicines · 2022Article
- Nonsense-mediated mRNA decay inhibition synergizes with MDM2 inhibition to suppress TP53 wild-type cancer cells in p53 isoform-dependent manner.Cell death discovery · 2022Article
- P63 and P73 Activation in Cancers with p53 Mutation.Biomedicines · 2022Review
- CRISPR-SCReT (CRISPR-Stop Codon Read Through) method to control Cas9 expression for gene editing.Gene therapy · 2022Article
- NanoLuc reporters identifyiScience · 2022Article
- Nonselective TRPC channel inhibition and suppression of aminoglycoside-induced premature termination codon readthrough by the small molecule AC1903.The Journal of biological chemistry · 2022Article
- Small molecule Y-320 stimulates ribosome biogenesis, protein synthesis, and aminoglycoside-induced premature termination codon readthrough.PLoS biology · 2021Article
- Effect of small molecule eRF3 degraders on premature termination codon readthrough.Nucleic acids research · 2021Article
- A Quick Guide to Small-Molecule Inhibitors of Eukaryotic Protein Synthesis.Biochemistry. Biokhimiia · 2020Review
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nonsense mutations constitute ~10% of TP53 mutations in cancer. They introduce a premature termination codon that gives rise to truncated p53 protein with impaired function. The aminoglycoside G418 can induce TP53 premature termination codon readthrough and thus increase cellular levels of full-length protein. Small molecule phthalimide derivatives that can enhance the readthrough activity of G418 have also been described. To determine whether readthrough enhancers exist among drugs that are already approved for use in humans, we tested seven antimalarial drugs for readthrough of the common R213X TP53 nonsense mutation in HDQ-P1 breast cancer cells. Mefloquine induced no TP53 readthrough activity as a single agent but it strongly potentiated readthrough by G418. The two enantiomers composing pharmaceutical mefloquine potentiated readthrough to similar levels in HDQ-P1 cells and also in SW900, NCI-H1688 and HCC1937 cancer cells with different TP53 nonsense mutations. Exposure to G418 and mefloquine increased p53 phosphorylation at Ser15 and P21 transcript levels following DNA damage, indicating p53 produced via readthrough was functional. Mefloquine does not appear to enhance readthrough via lysosomotropic effects as it did not significantly affect lysosomal pH, the cellular levels of G418 or its distribution in organellar or cytosolic fractions. The availability of a readthrough enhancer that is already approved for use in humans should facilitate study of the therapeutic potential of TP53 readthrough in preclinical cancer models.
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