ArticleJournal of the American Chemical Society2014
Irreversible inhibition of DNA polymerase β by small-molecule mimics of a DNA lesion.
Article in Journal of the American Chemical Society, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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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
15 citing papers in PubMed, 24 citations in OpenAlex.
- Noncompetitive Inhibition of DNA Polymerase β by a Nonnative Nucleotide.The Journal of organic chemistry · 2025Review
- Molecular editing ofRSC medicinal chemistry · 2024Article
- Article
- Base excision repair accessory factors in senescence avoidance and resistance to treatments.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- Suppression of DNA Polymerase β Activity Is Synthetically Lethal in BRCA1-Deficient Cells.ACS chemical biology · 2021Article
- Protein Domain Specific Covalent Inhibition of Human DNA Polymerase β.Chembiochem : a European journal of chemical biology · 2021Article
- Targeting protein-protein interactions in the DNA damage response pathways for cancer chemotherapy.RSC chemical biology · 2021Review
- Selective Inhibition of DNA Polymerase β by a Covalent Inhibitor.Journal of the American Chemical Society · 2021Article
- A Facile Semisynthesis and Evaluation of Garcinoic Acid and Its Analogs for the Inhibition of Human DNA Polymerase β.Molecules (Basel, Switzerland) · 2020Article
- Drugging the Cancers Addicted to DNA Repair.Journal of the National Cancer Institute · 2017Review
- Synergistic Effects of an Irreversible DNA Polymerase Inhibitor and DNA Damaging Agents on HeLa Cells.ACS chemical biology · 2017Article
- Honokiol Inhibits DNA Polymerases β and λ and Increases Bleomycin Sensitivity of Human Cancer Cells.Chemical research in toxicology · 2017Article
- Review
- DNA repair targeted therapy: The past or future of cancer treatment?Pharmacology & therapeutics · 2016Review
- Molecular mechanism of adenomatous polyposis coli-induced blockade of base excision repair pathway in colorectal carcinogenesis.Life sciences · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Abasic sites are ubiquitous DNA lesions that are mutagenic and cytotoxic but are removed by the base excision repair pathway. DNA polymerase β carries out two of the four steps during base excision repair, including a lyase reaction that removes the abasic site from DNA following incision of its 5'-phosphate. DNA polymerase β is overexpressed in cancer cells and is a potential anticancer target. Recently, DNA oxidized abasic sites that are produced by potent antitumor agents were shown to inactivate DNA polymerase β. A library of small molecules whose structures were inspired by the oxidized abasic sites was synthesized and screened for the ability to irreversibly inhibit DNA polymerase β. One candidate (3a) was examined more thoroughly, and modification of its phosphate backbone led to a molecule that irreversibly inactivates DNA polymerase β in solution (IC50 ≈ 21 μM), and inhibits the enzyme's lyase activity in cell lysates. A bisacetate analogue is converted in cell lysates to 3a. The bisacetate is more effective in cell lysates, more cytotoxic in prostate cancer cells than 3a and potentiates the cytotoxicity of methyl methanesulfonate between 2- and 5-fold. This is the first example of an irreversible inhibitor of the lyase activity of DNA polymerase β that works synergistically with a DNA damaging agent.
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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.