ArticleOncotarget2018
VX-984 is a selective inhibitor of non-homologous end joining, with possible preferential activity in transformed cells.
Article in Oncotarget, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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
22 citing papers in PubMed, 51 citations in OpenAlex.
- Targeting DNA-PK: medicinal chemistry insights into small-molecule inhibitor discovery and optimisation.RSC medicinal chemistry · 2026Review
- Review
- Inhibiting NHEJ: In-Silico Approach to Stratifying DNA-PK Inhibitors, Predicting Radio-Halogenation Potential of DNA-PK Inhibitors, and Assessing AlphaFold2 Prediction Accuracy.Bioengineering (Basel, Switzerland) · 2026Article
- Impeding the NHEJ Pathway for Overcoming Radioresistance in the Context of Precision Radiotherapy of Cancer.Pharmaceutics · 2026Review
- Deuteration of Six-Membered N-Heteroarenes: Chemistry and Applications.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Review
- Unlocking the Therapeutic Potential of DNA-PKcs in Cancer: Comprehensive Insights into Mechanisms and Clinical Applications.Cancers · 2025Review
- DNA-PKcs suppresses illegitimate chromosome rearrangements.Nucleic acids research · 2024Article
- High-efficiency transgene integration by homology-directed repair in human primary cells using DNA-PKcs inhibition.Nature biotechnology · 2024Article
- Deuterium in drug discovery: progress, opportunities and challenges.Nature reviews. Drug discovery · 2023Review
- Deuterodehalogenation Under Net Reductive or Redox-Neutral Conditions Enabled by Paired Electrolysis.Angewandte Chemie (International ed. in English) · 2023Article
- Development and Evolution of DNA-Dependent Protein Kinase Inhibitors toward Cancer Therapy.International journal of molecular sciences · 2022Review
- Perspective on the Use of DNA Repair Inhibitors as a Tool for Imaging and Radionuclide Therapy of Glioblastoma.Cancers · 2022Review
- Titanocene(III)-Catalyzed Precision Deuteration of Epoxides.Angewandte Chemie (International ed. in English) · 2022Article
- Enhancing anti-tumour innate immunity by targeting the DNA damage response and pattern recognition receptors in combination with radiotherapy.Frontiers in oncology · 2022Review
- Unexpected Substituent Effects in Spiro-Compound Formation: SteeringThe Journal of organic chemistry · 2021Article
- Exploiting DNA Damage Repair in Precision Cancer Therapy: BRCA1 as a Prime Therapeutic Target.Cancers · 2021Review
- DNA damage repair: historical perspectives, mechanistic pathways and clinical translation for targeted cancer therapy.Signal transduction and targeted therapy · 2021Review
- Targeting Stress-Response Pathways and Therapeutic Resistance in Head and Neck Cancer.Frontiers in oral health · 2021Review
- DNA damage response signaling pathways and targets for radiotherapy sensitization in cancer.Signal transduction and targeted therapy · 2020Review
- Radiation resistance in head and neck squamous cell carcinoma: dire need for an appropriate sensitizer.Oncogene · 2020Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
purposeDNA double-strand breaks (DSBs) can be repaired by non-homologous end joining (NHEJ) or homologous recombination (HR). We demonstrate the selectivity of VX-984, a DNA-PK inhibitor, using assays not previously reported. EXPERIMENTAL
designThe class switch recombination assay (CSR) in primary B cells was used to measure efficiency of NHEJ. A cellular reporter assay (U2OS EJ-DR) was used to assess the efficiency of HR and NHEJ in cells treated with VX-984. Immunofluorescence assays (IF) evaluated γ-H2AX foci for DSB repair kinetics in human astrocytes and T98G glioma cells. Western blotting was used to evaluate phosphorylation of DNA-PKcs substrates.
resultsWe found a dose-dependent reduction in CSR efficiency with VX-984, and through the EJ-DR assay, dramatic dose-dependent increases in HR and mNHEJ. Immunofluorescence assays showed an inability of malignant cells to resolve γ-H2AX foci in the presence of VX-984. Radiation-induced phosphorylation of DNA-PK substrates was further reduced by treatment with VX-984.
conclusionsVX-984 efficiently inhibits NHEJ, resulting in compensatory increases in alternative repair pathways, increases DSBs, and appears to affect transformed cells preferentially.
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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.