ArticleCancer biology & therapy2019
Discovery of a novel DNA polymerase inhibitor and characterization of its antiproliferative properties.
Article in Cancer biology & therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 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
9 citing papers in PubMed, 14 citations in OpenAlex.
- Interplay Between Poly(ADP-ribosyl)ation and Specific Inner Cellular Events That Suggest Combination Strategies for Overcoming PARP Inhibitor Resistance.Pharmaceutics · 2026Review
- Systematic Exploration of Small-Molecule Binding via a Large Language Model Trained on Textualized Protein-Ligand Interactions.Molecules (Basel, Switzerland) · 2025Article
- High-efficiency homology-directed insertion into the genome using the engineered homing endonuclease ARCUS.Nucleic acids research · 2025Article
- Abacavir enhances the efficacy of doxorubicin via inhibition of histone demethylase KDM5B in breast cancer.Scientific reports · 2025Article
- Review
- Emerging actionable targets to treat therapy-resistant colorectal cancers.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- Review
- PARP inhibitor resistance: the underlying mechanisms and clinical implications.Molecular cancer · 2020Review
- Precision medicine in pancreatic cancer: treating every patient as an exception.The lancet. Gastroenterology & hepatology · 2019Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Chromosomal duplication is targeted by various chemotherapeutic agents for the treatment of cancer. However, there is no specific inhibitor of DNA polymerases that is viable for cancer management. Through structure-based in silico screening of the ZINC database, we identified a specific inhibitor of DNA polymerase δ. The discovered inhibitor, Zelpolib, is projected to bind to the active site of Pol δ when it is actively engaged in DNA replication through interactions with DNA template and primer. Zelpolib shows robust inhibition of Pol δ activity in reconstituted DNA replication assays. Under cellular conditions, Zelpolib is taken up readily by cancer cells and inhibits DNA replication in assays to assess global DNA synthesis or single-molecule bases by DNA fiber fluorography. In addition, we show that Zelpolib displays superior antiproliferative properties to methotrexate, 5-flourouracil, and cisplatin in triple-negative breast cancer cell line, pancreatic cancer cell line and platinum-resistant pancreatic cancer cell line. Pol δ is not only involved in DNA replication, it is also a key component in many DNA repair pathways. Pol δ is the key enzyme responsible for D-loop extension during homologous recombination. Indeed, Zelpolib shows robust inhibition of homologous recombination repair of DNA double-strand breaks and induces "BRCAness" in HR-proficient cancer cells and enhances their sensitivity to PARP inhibitors.
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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.