ArticleBioorganic & medicinal chemistry letters2017
A triple exon-skipping luciferase reporter assay identifies a new CLK inhibitor pharmacophore.
Article in Bioorganic & medicinal chemistry letters, 2017. 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 14 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
14 citing papers in PubMed, 22 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
- Targeting RNA binding proteins with small-molecule inhibitors: Advances, challenges, and therapeutic opportunities.Acta pharmaceutica Sinica. B · 2026Review
- FeaSion decodes the regulatory landscape and functional diversity of RNA polymerase II CTD phosphorylation.Science advances · 2025Article
- Integrated bioinformatics combined with machine learning to analyze shared biomarkers and pathways in psoriasis and cervical squamous cell carcinoma.Frontiers in immunology · 2024Article
- Cdc2-like kinases: structure, biological function, and therapeutic targets for diseases.Signal transduction and targeted therapy · 2023Review
- SGC-CLK-1: A chemical probe for the Cdc2-like kinases CLK1, CLK2, and CLK4.Current research in chemical biology · 2023Article
- The "Janus-like" RNA-editing machinery in innate antiviral immunity.Current trends in immunology · 2022Article
- Therapeutic Targeting of Alternative Splicing: A New Frontier in Cancer Treatment.Frontiers in oncology · 2022Review
- Biology of the mRNA Splicing Machinery and Its Dysregulation in Cancer Providing Therapeutic Opportunities.International journal of molecular sciences · 2021Review
- Cdc-Like Kinases (CLKs): Biology, Chemical Probes, and Therapeutic Potential.International journal of molecular sciences · 2020Review
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- More than a messenger: Alternative splicing as a therapeutic target.Biochimica et biophysica acta. Gene regulatory mechanismsReview
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The splicing of pre-mRNA is a critical process in normal cells and is deregulated in cancer. Compounds that modulate this process have recently been shown to target a specific vulnerability in tumors. We have developed a novel cell-based assay that specifically activates luciferase in cells exposed to SF3B1 targeted compounds, such as sudemycin D6. This assay was used to screen a combined collection of approved drugs and bioactive compounds. This screening approach identified several active hits, the most potent of which were CGP-74514A and aminopurvalanol A, both have been reported to be cyclin-dependent kinases (CDKs) inhibitors. We found that these compounds, and their analogs, show significant cdc2-like kinase (CLK) inhibition and clear structure-activity relationships (SAR) at CLKs. We prepared a set of analogs and were able to 'dial out' the CDK activity and simultaneously developed CLK inhibitors with low nanomolar activity. Thus, we have demonstrated the utility of our exon-skipping assay and identified new molecules that exhibit potency and selectivity for CLK, as well as some structurally related dual CLK/CDK inhibitors.
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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.