ArticleOncogene2004
SU11752 inhibits the DNA-dependent protein kinase and DNA double-strand break repair resulting in ionizing radiation sensitization.
Article in Oncogene, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
32 citing papers in PubMed, 78 citations in OpenAlex.
- Targeting DNA-PK: medicinal chemistry insights into small-molecule inhibitor discovery and optimisation.RSC medicinal chemistry · 2026Review
- The interplay between DNA damage response and mitochondrial dysfunction in radiotherapy.Frontiers in oncology · 2025Review
- The future of cancer treatment: combining radiotherapy with immunotherapy.Frontiers in molecular biosciences · 2024Review
- Targeting the DNA Damage Response and DNA Repair Pathways to Enhance Radiosensitivity in Colorectal Cancer.Cancers · 2022Review
- 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
- Enhancing anti-tumour innate immunity by targeting the DNA damage response and pattern recognition receptors in combination with radiotherapy.Frontiers in oncology · 2022Review
- DNAPK Inhibition Preferentially Compromises the Repair of Radiation-induced DNA Double-strand Breaks in Chronically Hypoxic Tumor Cells in Xenograft Models.Molecular cancer therapeutics · 2021Article
- Combination Strategies to Improve Targeted Radionuclide Therapy.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2020Article
- Altering DNA Repair to Improve Radiation Therapy: Specific and Multiple Pathway Targeting.Frontiers in oncology · 2019Review
- Review
- DNA Damage Signalling and Repair Inhibitors: The Long-Sought-After Achilles' Heel of Cancer.Biomolecules · 2015Review
- Combining carbon ion irradiation and non-homologous end-joining repair inhibitor NU7026 efficiently kills cancer cells.Radiation oncology (London, England) · 2015Article
- Zerumbone increases oxidative stress in a thiol-dependent ROS-independent manner to increase DNA damage and sensitize colorectal cancer cells to radiation.Cancer medicine · 2015Article
- Chemotherapeutic compounds targeting the DNA double-strand break repair pathways: the good, the bad, and the promising.Frontiers in oncology · 2014Review
- Inhibiting the DNA damage response as a therapeutic manoeuvre in cancer.British journal of pharmacology · 2013Review
- Single-cell microarray enables high-throughput evaluation of DNA double-strand breaks and DNA repair inhibitors.Cell cycle (Georgetown, Tex.) · 2013Article
- DNA repair dysregulation from cancer driver to therapeutic target.Nature reviews. Cancer · 2012Review
- Characterization of DDRI-18 (3,3'-(1H,3'H-5,5'-bibenzo[d]imidazole-2,2'-diyl)dianiline), a novel small molecule inhibitor modulating the DNA damage response.British journal of pharmacology · 2012Article
- Strategies for targeting the DNA damage response for cancer therapeutics.Chinese journal of cancer · 2012Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Loss of the DNA-dependent protein kinase (DNA-PK) results in increased sensitivity to ionizing radiation due to inefficient repair of DNA double-strand breaks. Overexpression of DNA-PK in tumor cells conversely results in resistance to ionizing radiation. It is therefore possible that inhibition of DNA-PK will enhance the preferential killing of tumor cells by radiotherapy. Available inhibitors of DNA-PK, like wortmannin, are cytotoxic and stop the cell cycle because they inhibit phoshatidylinositol-3-kinases at 100-fold lower concentrations required to inhibit DNA-PK. In an effort to develop a specific DNA-PK inhibitor, we have characterized SU11752, from a three-substituted indolin-2-ones library. SU11752 and wortmannin were equally potent inhibitors of DNA-PK. In contrast, inhibition of the phoshatidylinositol-3-kinase p110gamma required 500-fold higher concentration of SU11752. Thus, SU11752 was a more selective inhibitor of DNA-PK than wortmannin. Inhibition kinetics and a direct assay for ATP binding showed that SU11752 inhibited DNA-PK by competing with ATP. SU11752 inhibited DNA double-strand break repair in cells and gave rise to a five-fold sensitization to ionizing radiation. At concentrations of SU11752 that inhibited DNA repair, cell cycle progression was still normal and ATM kinase activity was not inhibited. We conclude that SU11752 defines a new class of drugs that may serve as a starting point for the development of specific DNA-PK inhibitors.
Indexed as
Identifiers
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.