ArticleThe Journal of biological chemistry2014
Identification of small molecule inhibitors of pre-mRNA splicing.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 45 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.
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Who cites it
45 citing papers in PubMed, 74 citations in OpenAlex.
- Deconvoluting the multi-faceted roles of alternative splicing events in cancer: From underlying mechanisms to innovative therapeutics.Acta pharmaceutica Sinica. B · 2026Review
- The splice of life: an isoform-centric view of disease, technology, and therapeutics.The Journal of clinical investigation · 2026Review
- Targeting RNA binding proteins with small-molecule inhibitors: Advances, challenges, and therapeutic opportunities.Acta pharmaceutica Sinica. B · 2026Review
- Discovery of small molecules against porcine reproductive and respiratory syndrome virus replication by targeting NendoU activity.Journal of virology · 2025Article
- Maize splicing-mediated mRNA surveillance impeded by sugarcane mosaic virus-coded pathogenic protein NIa-Pro.Science advances · 2024Article
- Nuclear RNA-related processes modulate the assembly of cytoplasmic RNA granules.Nucleic acids research · 2024Article
- The Nitro Group Reshapes the Effects of Pyrido[3,4-Cancers · 2024Article
- Isoginkgetin and Madrasin are poor splicing inhibitors.PloS one · 2024Article
- MEN1 is a regulator of alternative splicing and prevents R-loop-induced genome instability through suppression of RNA polymerase II elongation.Nucleic acids research · 2023Article
- RNA Transcript Diversity in Neuromuscular Research.Journal of neuromuscular diseases · 2023Review
- Regulating the regulator: a survey of mechanisms from transcription to translation controlling expression of mammalian cell cycle kinase Aurora A.Open biology · 2022Review
- Targeting the splicing factor NONO inhibits GBM progression through GPX1 intron retention.Theranostics · 2022Article
- Differential Splicing of Skipped Exons Predicts Drug Response in Cancer Cell Lines.Genomics, proteomics & bioinformatics · 2021Article
- Biology of the mRNA Splicing Machinery and Its Dysregulation in Cancer Providing Therapeutic Opportunities.International journal of molecular sciences · 2021Review
- Hypoxia-induced alternative splicing in human diseases: the pledge, the turn, and the prestige.Cellular and molecular life sciences : CMLS · 2021Review
- Cross-species identification of PIP5K1-, splicing- and ubiquitin-related pathways as potential targets for RB1-deficient cells.PLoS genetics · 2021Article
- Article
- The Roles of Non-coding RNA in the Development and Regeneration of Hair Follicles: Current Status and Further Perspectives.Frontiers in cell and developmental biology · 2021Review
- Functional Diversification of SRSF Protein Kinase to Control Ubiquitin-Dependent Neurodevelopmental Signaling.Developmental cell · 2020Article
- New Insights in RBM20 Cardiomyopathy.Current heart failure reports · 2020Review
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Eukaryotic pre-mRNA splicing is an essential step in gene expression for all genes that contain introns. In contrast to transcription and translation, few well characterized chemical inhibitors are available with which to dissect the splicing process, particularly in cells. Therefore, the identification of specific small molecules that either inhibit or modify pre-mRNA splicing would be valuable for research and potentially also for therapeutic applications. We have screened a highly curated library of 71,504 drug-like small molecules using a high throughput in vitro splicing assay. This identified 10 new compounds that both inhibit pre-mRNA splicing in vitro and modify splicing of endogenous pre-mRNA in cells. One of these splicing modulators, DDD00107587 (termed "madrasin," i.e. 2-((7methoxy-4-methylquinazolin-2-yl)amino)-5,6-dimethylpyrimidin-4(3H)-one RNAsplicing inhibitor), was studied in more detail. Madrasin interferes with the early stages of spliceosome assembly and stalls spliceosome assembly at the A complex. Madrasin is cytotoxic at higher concentrations, although at lower concentrations it induces cell cycle arrest, promotes a specific reorganization of subnuclear protein localization, and modulates splicing of multiple pre-mRNAs in both HeLa and HEK293 cells.
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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.