ArticleBritish journal of cancer2005
Preclinical pharmacokinetics and metabolism of a novel prototype DNA-PK inhibitor NU7026.
Article in British journal of cancer, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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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
52 citing papers in PubMed, 97 citations in OpenAlex.
- Targeting BRCA1-BER deficient breast cancer by ATM or DNA-PKcs blockade either alone or in combination with cisplatin for personalized therapy.Molecular oncology · 2015Trial
- PTK7 scaffolds DNA-PKcs to promote DNA damage response and immune evasion in triple-negative breast cancer.Oncogene · 2026Article
- Unlocking the Therapeutic Potential of DNA-PKcs in Cancer: Comprehensive Insights into Mechanisms and Clinical Applications.Cancers · 2025Review
- Combined Ribociclib and NU7026 administration enhances radio-sensitivity by inhibiting DNA repair in prostate cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Secrets of DNA-PKcs beyond DNA repair.NPJ precision oncology · 2024Review
- Integrated single-cell and bulk RNA sequencing reveals immune-related SPP1+ macrophages as a potential strategy for predicting the prognosis and treatment of liver fibrosis and hepatocellular carcinoma.Frontiers in immunology · 2024Article
- Improving the sensitivity of in vivo CRISPR off-target detection with DISCOVER-Seq.Nature methods · 2023Article
- DNA Damage Response Alterations in Ovarian Cancer: From Molecular Mechanisms to Therapeutic Opportunities.Cancers · 2023Review
- An mTOR and DNA-PK dual inhibitor CC-115 hinders non-small cell lung cancer cell growth.Cell death discovery · 2022Article
- Development and Evolution of DNA-Dependent Protein Kinase Inhibitors toward Cancer Therapy.International journal of molecular sciences · 2022Review
- Radiation affects glutathione redox reaction by reduced glutathione peroxidase activity in human fibroblasts.Journal of radiation research · 2022Article
- DNA-PKcs: A Targetable Protumorigenic Protein Kinase.Cancer research · 2022Review
- Review
- Genetic landscape of T cells identifies synthetic lethality for T-ALL.Communications biology · 2021Article
- DNA damage repair in glioblastoma: current perspectives on its role in tumour progression, treatment resistance and PIKKing potential therapeutic targets.Cellular oncology (Dordrecht, Netherlands) · 2021Review
- Review
- Targeting Stress-Response Pathways and Therapeutic Resistance in Head and Neck Cancer.Frontiers in oral health · 2021Review
- Ku80-Targeted pH-Sensitive Peptide-PNA Conjugates Are Tumor Selective and Sensitize Cancer Cells to Ionizing Radiation.Molecular cancer research : MCR · 2020Article
- Radiation resistance in head and neck squamous cell carcinoma: dire need for an appropriate sensitizer.Oncogene · 2020Review
- DNA-PKcs: A Multi-Faceted Player in DNA Damage Response.Frontiers in genetics · 2020Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In this study we investigated the in vitro time dependence of radiosensitisation, pharmacokinetics and metabolism of NU7026, a novel inhibitor of the DNA repair enzyme DNA-dependent protein kinase (DNA-PK). At a dose of 10 muM, which is nontoxic to cells per se, a minimum NU7026 exposure of 4 h in combination with 3 Gy radiation is required for a significant radiosensitisation effect in CH1 human ovarian cancer cells. Following intravenous administration to mice at 5 mg kg(-1), NU7026 underwent rapid plasma clearance (0.108 l h(-1)) and this was largely attributed to extensive metabolism. Bioavailability following interperitoneal (i.p.) and p.o. administration at 20 mg kg(-1) was 20 and 15%, respectively. Investigation of NU7026 metabolism profiles in plasma and urine indicated that the compound undergoes multiple hydroxylations. A glucuronide conjugate of a bis-hydroxylated metabolite represented the major excretion product in urine. Identification of the major oxidation site as C-2 of the morpholine ring was confirmed by the fact that the plasma clearance of NU7107 (an analogue of NU7026 methylated at C-2 and C-6 of the morpholine ring) was four-fold slower than that of NU7026. The pharmacokinetic simulations performed predict that NU7026 will have to be administered four times per day at 100 mg kg(-1) i.p. in order to obtain the drug exposure required for radiosensitisation.
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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.