ArticlePloS one2014
Identification of a novel function of CX-4945 as a splicing regulator.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 96 citations in OpenAlex.
- An Orally Available Derivative of a Specific CK2 Inhibitor for Regulating Circadian Rhythms and Acute Myeloid Leukemia.Precision chemistry · 2026Article
- Combining Temozolomide with a Selective CK2 Inhibitor Results in Anti-Tumour Effects in Glioblastoma Cell Lines.Molecules (Basel, Switzerland) · 2026Article
- Switching off CK2-mediated activation of survivin offers new therapeutic opportunities in neuroblastoma.Experimental & molecular medicine · 2026Article
- Acidosis promotes exon skipping through sequestering SR-rich splicing factors in nuclear speckles.Frontiers in molecular biosciences · 2026Article
- Towards the targeted protein degradation of CK2: design and synthesis of CAM4066-based PROTACs.Beilstein journal of organic chemistry · 2026Article
- Comparative Efficacy of CK2 Inhibitors CX-4945 and SGC-CK2-2 on CK2 Signaling.International journal of molecular sciences · 2025Article
- CK2 in the spotlight: decoding its role in hematological malignancies and therapeutic applications.Discover oncology · 2025Review
- Epigenetic Regulation and Therapeutic Targeting of Alternative Splicing Dysregulation in Cancer.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Research towards selective inhibition of the CLK3 kinase.Beilstein journal of organic chemistry · 2025Article
- CK2 activity is crucial for proper glucagon expression.Diabetologia · 2024Article
- Recent Advances in the Discovery of CK2 Inhibitors.ACS omega · 2024Review
- Chemical proteomics reveals the target landscape of 1,000 kinase inhibitors.Nature chemical biology · 2024Article
- Scoping Pleiotropy of CK2 in Musculoskeletal Disorders for a Novel Targeting Approach.Kinases and phosphatases · 2024Article
- Cancer selective cell death induction by a bivalent CK2 inhibitor targeting the ATP site and the allosteric αD pocket.iScience · 2024Article
- Development of 5-hydroxybenzothiophene derivatives as multi-kinase inhibitors with potential anti-cancer activity.Future medicinal chemistry · 2024Article
- Cdc2-like kinases: structure, biological function, and therapeutic targets for diseases.Signal transduction and targeted therapy · 2023Review
- Comparison of CX-4945 and SGC-CK2-1 as inhibitors of CSNK2 using quantitative phosphoproteomics: Triple SILAC in combination with inhibitor-resistant CSNK2.Current research in chemical biology · 2023Article
- SGC-CLK-1: A chemical probe for the Cdc2-like kinases CLK1, CLK2, and CLK4.Current research in chemical biology · 2023Article
- Motif-Targeting Phosphoproteome Analysis of Cancer Cells for Profiling Kinase Inhibitors.Cancers · 2022Article
- Preclinical Evaluation of Trabectedin in Combination With Targeted Inhibitors for Treatment of Metastatic Uveal Melanoma.Investigative ophthalmology & visual science · 2022Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alternative splicing is a nearly ubiquitous versatile process that controls gene expression and creates numerous protein isoforms with different functions from a single gene. The significance of alternative splicing has been confirmed by the increasing number of human diseases that are caused by misregulation of splicing events. Very few compounds, however, have been reported to act as inhibitors of alternative splicing, and their potential clinical use needs to be evaluated. Here, we report that CX-4945, a previously well-characterized inhibitor of casein kinase 2 (CK2) and a molecule currently in clinical trials (Phase II) for cancer treatment, regulates splicing in mammalian cells in a CK2-independent manner. Transcriptome-wide analysis using exon array also showed a widespread alteration in alternative splicing of numerous genes. We found that CX-4945 potently inhibits the Cdc2-like kinases (Clks) in vitro and in turn, leads to suppression of the phosphorylation of serine/arginine-rich (SR) proteins in mammalian cells. Surprisingly, the overall efficacy of CX-4945 on Clks (IC50 = 3-90 nM) was stronger than that of TG-003, the strongest inhibitor reported to date. Of the Clks, Clk2 was most strongly inhibited by CX-4945 in an ATP-competitive manner. Our research revealed an unexpected activity of the drug candidate CX-4945 as a potent splicing modulator and also suggested a potential application for therapy of diseases caused by abnormal splicing.
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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.