ArticleMolecular cancer research : MCR2009
A novel inhibitor of DNA polymerase beta enhances the ability of temozolomide to impair the growth of colon cancer cells.
Article in Molecular cancer research : MCR, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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
28 citing papers in PubMed, 54 citations in OpenAlex.
- Noncompetitive Inhibition of DNA Polymerase β by a Nonnative Nucleotide.The Journal of organic chemistry · 2025Review
- Impact of DNA ligase inhibition on the nick sealing of polβ nucleotide insertion products at the downstream steps of base excision repair pathway.Mutagenesis · 2024Article
- Molecular editing ofRSC medicinal chemistry · 2024Article
- EEPD1 promotes repair of oxidatively-stressed replication forks.NAR cancer · 2023Article
- In Vitro Reconstitutive Base Excision Repair (BER) Assay.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Base excision repair accessory factors in senescence avoidance and resistance to treatments.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- Molecular disruption of DNA polymerase β for platinum sensitisation and synthetic lethality in epithelial ovarian cancers.Oncogene · 2021Article
- DNA alkylation lesion repair: outcomes and implications in cancer chemotherapy.Journal of Zhejiang University. Science. B · 2021Review
- The splicing component ISY1 regulates APE1 in base excision repair.DNA repair · 2020Article
- Targeting Base Excision Repair Glycosylases with DNA Containing Transition State Mimics Prepared via Click Chemistry.ACS chemical biology · 2019Article
- Targeting DNA repair and replication stress in the treatment of ovarian cancer.International journal of clinical oncology · 2017Review
- Honokiol Inhibits DNA Polymerases β and λ and Increases Bleomycin Sensitivity of Human Cancer Cells.Chemical research in toxicology · 2017Article
- Small molecule inhibitors uncover synthetic genetic interactions of human flap endonuclease 1 (FEN1) with DNA damage response genes.PloS one · 2017Article
- Screening of Chonemorpha fragrans Bioactive Extracts for Cytotoxicity Potential and Inhibition Studies of Key Enzymes Involved in Replication.Pharmacognosy magazine · 2016Article
- DNA repair targeted therapy: The past or future of cancer treatment?Pharmacology & therapeutics · 2016Review
- Small Molecule Inhibitors of 8-Oxoguanine DNA Glycosylase-1 (OGG1).ACS chemical biology · 2015Article
- Molecular mechanism of adenomatous polyposis coli-induced blockade of base excision repair pathway in colorectal carcinogenesis.Life sciences · 2015Review
- Article
- Metal-dependent conformational activation explains highly promutagenic replication across O6-methylguanine by human DNA polymerase β.Journal of the American Chemical Society · 2014Article
- Developing an in silico model of the modulation of base excision repair using methoxyamine for more targeted cancer therapeutics.IET systems biology · 2013Article
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 4 institutions in 1 country.
Funding
Abstract
The recent emerging concept to sensitize cancer cells to DNA-alkylating drugs is by inhibiting various proteins in the base excision repair (BER) pathway. In the present study, we used structure-based molecular docking of DNA polymerase beta (Pol-beta) and identified a potent small molecular weight inhibitor, NSC-666715. We determined the specificity of this small molecular weight inhibitor for Pol-beta by using in vitro activities of APE1, Fen1, DNA ligase I, and Pol-beta-directed single-nucleotide and long-patch BER. The binding specificity of NSC-666715 with Pol-beta was also determined by using fluorescence anisotropy. The effect of NSC-666715 on the cytotoxicity of the DNA-alkylating drug temozolomide (TMZ) to colon cancer cells was determined by in vitro clonogenic and in vivo xenograft assays. The reduction in tumor growth was higher in the combination treatment relative to untreated or monotherapy treatment. NSC-666715 showed a high specificity for blocking Pol-beta activity. It blocked Pol-beta-directed single-nucleotide and long-patch BER without affecting the activity of APE1, Fen1, and DNA ligase I. Fluorescence anisotropy data suggested that NSC-666715 directly and specifically interacts with Pol-beta and interferes with binding to damaged DNA. NSC-666715 drastically induces the sensitivity of TMZ to colon cancer cells both in in vitro and in vivo assays. The results further suggest that the disruption of BER by NSC-666715 negates its contribution to drug resistance and bypasses other resistance factors, such as mismatch repair defects. Our findings provide the "proof-of-concept" for the development of highly specific and thus safer structure-based inhibitors for the prevention of tumor progression and/or treatment of colorectal cancer.
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.